ORCID Profile
0000-0003-4720-0280
Current Organisations
Mothers and Babies Research Center (Hunter Medical Research Institute)
,
University of Newcastle Australia
,
John Hunter Hospital
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Publisher: IMR Press
Date: 2012
DOI: 10.2741/3953
Abstract: Corticotropin Releasing Hormone (CRH), a 41-amino acid peptide, is a major regulator of hypothalamic-pituitary-adrenal axis function. CRH also has important roles in several processes pertaining to pregnancy and parturition, including being a possible regulator of gestational length and predictor of pre-term birth. Regulation of the CRH promoter exhibits some tissue-specificities, the most well characterized ex le being glucocorticoids, which can stimulate placental CRH production but suppress hypothalamic CRH. In the last decade there has been growing interest in the role of epigenetic regulation of gene expression. Modification of the structure of chromatin is an ex le of epigenetic change affecting gene expression. We have found that inhibition of histone deacetylases results in an increase in CRH expression in the AtT20 pituitary cell line, but a decrease in CRH expression in the placenta. In this paper we review tissue specific differences in CRH gene expression, and discuss how epigenetic chromatin modification mechanisms can relate to tissue specific differences in expression of CRH.
Publisher: Elsevier BV
Date: 1999
DOI: 10.1016/S0002-9378(99)70707-6
Abstract: Near the end of human pregnancy the concentration of placental corticotropin-releasing hormone in maternal blood rises exponentially. The rate of elevation of corticotropin-releasing hormone and its duration through time have been linked to the time of onset of labor. Paradoxically, although glucocorticoids are known to inhibit corticotropin-releasing hormone production within the hypothalamic-pituitary-adrenal axis, cortisol actually increases corticotropin-releasing hormone levels in several areas outside the hypothalamus, including the placenta. Placental corticotropin-releasing hormone may be an important component of a system that controls the normal maturation of the fetus and signals the initiation of labor. Abnormal elevations in corticotropin-releasing hormone, which may be a hormonal response to stressors arising in either the mother, placenta, or fetus, may prove to participate in the premature onset of parturition.
Publisher: American Chemical Society (ACS)
Date: 07-03-2022
Publisher: Elsevier BV
Date: 03-1989
DOI: 10.1016/0196-9781(89)90061-2
Abstract: Experiments were conducted which compared the in vivo effects of beta-endorphin (BEP), gamma-endorphin (gamma EP), methionine-enkephalin (Met-ENK), and acetylated BEP(1-27) on the in vitro proliferative response of rat spleen cells to concanavalin A (ConA). In addition, the influence of BEP administration on the primary and secondary antibody-forming cell (AFC) response to the soluble antigen keyhole-limpet hemocyanin (KLH) was examined. Intravenous administration of BEP enhanced the spleen cell proliferative response to ConA assessed 3 hr after a single bolus infusion. Conversely, infusion with AcBEP(1-27) suppressed the proliferative response, whereas no effects of intravenous gamma EP or Met-ENK treatment were observed. The enhancing effect of BEP administration was not detectable 24 hr after a single infusion, but could be maintained over a 44 hr period by multiple infusions. The primary AFC response to KLH was suppressed by a dose of 1 nmole BEP only. On the other hand, the secondary IgG AFC response to KLH was enhanced by 10 pmoles BEP, while the IgM and IgA AFC responses remained unaltered by BEP treatment. The anamnestic in vitro proliferative response of spleen cells cultured with KLH was not altered if BEP was administered at the time of secondary KLH immunization. These results extend previous observations of BEP-induced modulation of in vitro immune function by demonstrating that opioid and nonopioid forms of BEP administered in vivo alter the capacity of spleen cells to proliferate and develop antibody responses to antigen.
Publisher: Springer Science and Business Media LLC
Date: 21-10-2016
DOI: 10.1007/S10439-016-1749-5
Abstract: Research insights into uterine function and the mechanisms of labour have been hindered by the lack of suitable animal and cellular models. The use of traditional culturing methods limits the exploration of complex uterine functions, such as cell interactions, connectivity and contractile behaviour, as it fails to mimic the three-dimensional (3D) nature of uterine cell interactions in vivo. Animal models are an option, however, use of these models is constrained by ethical considerations as well as translational limitations to humans. Evidence indicates that these limitations can be overcome by using 3D culture systems, or 3D Bioprinters, to model the in vivo cytological architecture of the tissue in an in vitro environment. 3D cultured or 3D printed cells can be used to form an artificial tissue. This artificial tissue can not only be used as an appropriate model in which to study cellular function and organisation, but could also be used for regenerative medicine purposes including organ or tissue transplantation, organ donation and obstetric care. The current review describes recent developments in cell culture that can facilitate the development of myometrial 3D structures and tissue engineering applications.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-1993
DOI: 10.1097/00006254-199304000-00001
Abstract: Only recently has the first disease-modifying therapy been approved for children with multiple sclerosis (MS) and practice patterns including substantial off-label use have evolved. Understanding attitudes towards treatment of paediatric MS and whether this has changed due to the ongoing COVID-19 pandemic is vital to guide future therapeutic trials and for developing guidelines that reflect practice. We performed an online survey within the International Paediatric Multiple Sclerosis Study Group between July and September 2020. The survey was sent to 130 members from 25 countries and consisted of five sections: demographic data, treatment, disease modifying therapies and COVID-19, outcome and three patient cases. The survey was completed by 66 members (51%), both paediatric neurologists and adult neurologists. Fingolimod and β-interferons were the most frequently used disease-modifying therapies, especially among paediatric neurologists. Almost a third (31%) of respondents had altered their prescribing practice due to COVID-19, in particular at the beginning of the pandemic. The survey results indicate a tendency of moving from the traditional escalation therapy starting with injectables towards an early start with newer, highly effective disease modifying therapies. The COVID-19 pandemic only slightly affected prescribing patterns and treatment choices in paediatric MS.
Publisher: Elsevier BV
Date: 02-2000
DOI: 10.1016/S0002-9378(00)70236-5
Abstract: Fetal fibronectin bedside testing has been proposed as a diagnostic tool for the accurate diagnosis of preterm labor. The study objective was to determine whether the introduction of routine fetal fibronectin bedside testing affected costs and transfer rates from referral district hospitals to a tertiary obstetric hospital, as well as direct admissions to a tertiary referral hospital. We performed an 18-month prospective audit of fetal fibronectin use in 9 referral hospitals and one university maternal-fetal medicine unit. Data collected were delivery details and cervical dilatation at admission. Cost savings in terms of transport costs for patients with a negative fetal fibronectin result who were not transferred or admitted to the tertiary center were calculated for interhospital transfer (road ambulance or fixed-wing retrieval). One hundred fifty-one patients had a presumptive diagnosis of threatened preterm labor. Forty-five patients had a positive fetal fibronectin result and 106 had a negative fetal fibronectin result (3 with cervical dilatation >/=3 cm). Eleven (24%) patients with a positive fetal fibronectin result were delivered within 7 days, and 5 (5%) with a negative fetal fibronectin result were delivered within 7 days. One patient was delivered at 34 weeks, and the remaining patients were delivered at or after 36 weeks' gestation. All 3 patients with negative fetal fibronectin results with cervical dilatation of >/=3 cm were delivered within 5 days, leaving 2 (1.9%) patients (with closed cervices and negative fetal fibronectin results) being delivered 5 days after the fetal fibronectin testing. Ninety percent of the patients admitted to a referral hospital with threatened preterm labor who had a negative fetal fibronectin result were not transferred thus an unnecessary transfer was avoided, with cost savings ranging from $30,297 for road and fixed-wing transport. A negative fetal fibronectin result is not helpful if cervical dilatation is present, and these patients should be treated as having a high risk of preterm delivery. The use of a fetal fibronectin test was associated with a 90% reduction in maternal transfer and can substantially reduce the costs and inconvenience associated with unnecessary transfer.
Publisher: American Astronomical Society
Date: 10-03-2016
Publisher: Oxford University Press (OUP)
Date: 15-02-2021
Abstract: We describe the ongoing Relativistic Binary programme (RelBin), a part of the MeerTime large survey project with the MeerKAT radio telescope. RelBin is primarily focused on observations of relativistic effects in binary pulsars to enable measurements of neutron star masses and tests of theories of gravity. We selected 25 pulsars as an initial high priority list of targets based on their characteristics and observational history with other telescopes. In this paper, we provide an outline of the programme, and present polarization calibrated pulse profiles for all selected pulsars as a reference catalogue along with updated dispersion measures. We report Faraday rotation measures for 24 pulsars, twelve of which have been measured for the first time. More than a third of our selected pulsars show a flat position angle swing confirming earlier observations. We demonstrate the ability of the Rotating Vector Model, fitted here to seven binary pulsars, including the Double Pulsar (PSR J0737–3039A), to obtain information about the orbital inclination angle. We present a high time resolution light curve of the eclipse of PSR J0737–3039A by the companion’s magnetosphere, a high-phase-resolution position angle swing for PSR J1141–6545, an improved detection of the Shapiro delay of PSR J1811–2405, and pulse scattering measurements for PSRs J1227–6208, J1757–1854, and J1811–1736. Finally, we demonstrate that timing observations with MeerKAT improve on existing data sets by a factor of, typically, 2–3, sometimes by an order of magnitude.
Publisher: The Endocrine Society
Date: 17-05-2021
Abstract: Human and animal studies suggest that hypothalamic-pituitary-adrenal axis (HPA-A) function may be programmed in utero however, these findings are inconsistent. Given the powerful metabolic actions of cortisol, it is important to clarify the influence of early life on adult HPA-A function. To determine the relationship between fetal growth and HPA-A stress response to a psychosocial stressor in young adults. Multigenerational, prospective cohort study (the Raine Study) conducted between 1989 and 1991. King Edward Memorial Hospital, Perth, Western Australia, Australia. A total of 917 participants aged 18 years from Gen2 of the Raine Study. Measures of hypothalamic-pituitary-adrenal axis function before and after exposure to the Trier Social Stress Test. In fully adjusted models, an inverse linear relationship was observed between birthweight and plasma measures of (1) baseline cortisol (β = -0.90%, 95% CI: -1.73 to -0.07 P = 0.03) (2) peak cortisol (β = -0.78%, 95% CI -1.51 to -0.06 P = 0.03) (3) area under the curve with respect to ground (β = -0.89%, 95% CI -1.60 to -0.18 P = 0.01) and (4) adrenal sensitivity (β = -1.02, 95% CI: -1.85 to -0.18 P = 0.02). Similar results were demonstrated for percent optimal birthweight. No consistent quadratic relationships were identified. No associations were found between measures of fetal adiposity and HPA-A function at age 18 years, or fetal growth and HPA-A response pattern. Removal of anticipatory responders from the models substantially attenuated the observed relationships. We observed an inverse linear relationship between fetal growth and HPA-A function at age 18 years. This differs from the inverse parabolic relationship (inverted U curve) reported in adults of advanced age. Altered adrenal sensitivity may underlie this relationship.
Publisher: Oxford University Press (OUP)
Date: 07-01-2013
DOI: 10.1111/NURE.12003
Abstract: Micronutrient status during pregnancy influences maternal and fetal health, birth outcomes, and the risk of chronic disease in offspring. Research reporting dietary intake during pregnancy in nationally representative population s les, however, is limited. This review summarizes the micronutrient intakes of pregnant women from developed countries and compares them with relevant national recommendations. A systematic search without date limits was conducted. All studies reporting the micronutrient intakes of pregnant women were considered, irrespective of design. Two authors independently identified studies for inclusion and assessed methodological quality. Nutritional adequacy was summarized, with confounding factors considered. Meta-analysis data are reported for developed countries collectively, by geographical region, and by dietary methodology. Pregnant women in developed countries are at risk of suboptimal micronutrient intakes. Folate, iron, and vitamin D intakes were consistently below nutrient recommendations in each geographical region, and calcium intakes in Japan were below the Japanese recommendations and the average intake levels in other developed countries. Research examining the implications of potential nutrient insufficiency on maternal and offspring health outcomes is needed along with improvements in the quality of dietary intake reporting.
Publisher: Public Library of Science (PLoS)
Date: 09-03-2017
Publisher: Hindawi Limited
Date: 12-02-2014
DOI: 10.1002/DA.22245
Abstract: Successful parenting requires maternal behaviors that promote infant survival such as protection from predators. In animal studies, oxytocin (OT) has been linked to maternal aggression to protect offspring. No human study has explored this topic. Mothers with a diagnosis of postnatal depression (PND) are at higher risk of neglecting their infants. We hypothesized that intranasal OT administration would increase the protective behaviors of mothers with PND, toward their infants. Sixteen mothers with a diagnosis of PND participated in a double-blind, randomized-controlled, within-subject pilot study. Participants received intranasal OT during one visit and placebo spray on the alternate visit. Maternal protective behavior toward their infant was measured, in the presence of a socially intrusive stranger. The enthusiastic stranger paradigm stimulated participants' protective responses in the presence of an intrusive stranger. Furthermore, this protective response of mothers with a diagnosis of PND was increased in the OT condition. The study introduces a new paradigm, the enthusiastic stranger paradigm, which may be used to examine a neglected type of parental behavior, that is, protection of offspring. The protective response of mothers with PND increased, in line with the 'tend and defend' effects of OT in animal models. In future work it should be tested whether this protection effect can also be found in nonclinical s les, or whether it is specific for clinically depressed mothers.
Publisher: The Endocrine Society
Date: 08-1994
DOI: 10.1210/JCEM.79.2.8045990
Abstract: The vasoactive effects of corticotropin-releasing hormone (CRH) in the human fetal-placental circulation in vitro have been investigated. Single lobules of term placentae were bilaterally perfused with constant flows of Krebs' solution (maternal and fetal, 5 ml/min, 95% O2, 5% CO2, 37 degrees C, pH 7.3) and changes in fetal-placental arterial perfusion pressure measured. Effects of human (hCRH) and ovine (oCRH) CRH were examined during submaximal vasoconstriction (100-120 mmHg) of the fetal-placental vasculature induced by prostaglandin F2 alpha (PGF2 alpha), (0.7-2 mumol/L). During infusion of hCRH or oCRH (24-7000 pmol/L) a concentration-dependent vasodilatation was observed. Human CRH and oCRH were equipotent as vasodilator agents (regression analysis P > 0.05 n = 5). The vasodilator response curves to human and ovine CRH were compared to prostacyclin (PGI2) (1.2-1180 nmol/L). Human and oCRH were 53 times more potent than PGI2 (regression analysis, P < 0.05 n = 5). These results indicate that CRH has powerful vasodilator properties in the human fetal-placental circulation and may play a role in control of placental vascular resistance to blood flow.
Publisher: Elsevier BV
Date: 03-2001
Publisher: Informa UK Limited
Date: 1988
DOI: 10.3109/09513598809023617
Abstract: Corticotropin-releasing hormone (CRH) immunoreactivity (IR) is present in the blood of women in the 3rd trimester of pregnancy and in placental extracts. We have used a placental fragment superfusion system to investigate the release of CRH from fresh placental tissue. Fragments of normal term placenta were mixed with Biogel P2, packed into minicolumns and superfused with carbogen-gassed Earles buffer at 37 degrees C. The rheology of the superfusion system was determined and the oxygen consumption of the superfused placental fragments indicated viability of the tissue preparation over a 5-hour time span. CRH IR in the eluate was measured by radioimmunoassay (RIA) using the 41 residue synthetic peptide human, rat CRH-41 (h, r CRH-41) as the standard, 125I labelled Tyr- h, r CRH as the tracer and rabbit anti-ovine CRH as the antibody. The sensitivity of the assay is 2 pM. Size exclusion chromatography on Sephadex G-50 of the placental column eluate displayed one major peak of CRH IR which co-eluted with that of h, r CRH. Placental fragment superfusate displayed potent CRH bioactivity as assessed by beta-endorphin secretion from ovine pituitary cells. Replacing the superfusing medium of the placental fragments with 45 mM KCl resulted in a prompt increase in the release of CRH IR. These results indicate that placental cells in vitro secrete a molecule of similar molecular weight, immunoreactivity and bioactivity to h, r CRH and that the rate of secretion may be regulated.
Publisher: The Endocrine Society
Date: 06-2002
Abstract: Human parturition is effected by a cascade of factors, of which many are unknown. We aim to identify the genes that are changed by labor in the human myometrium by suppression subtractive hybridization. We also seek to ascertain whether these genes are differentially expressed in the myometrium at the upper or fundal and lower segments of the uterus. Term myometrial tissues were obtained from laboring and nonlaboring women undergoing cesarean section after obtaining informed consent. Total RNA was used in suppression subtractive hybridization (CLONTECH PCR Select) to produce two subtracted cDNA libraries enriched for genes expressed during or before labor, labor and not-in-labor libraries, respectively. Dot blot screening of 400 positive clones, constituting 20% of the two subtracted libraries, revealed 30 differentially expressed clones, 14 of which were up-regulated by labor. Among the 10 known genes that were up-regulated in labor, 6 had apparent immune regulatory and inflammatory roles. Three are well-known inflammatory mediators and modulators that were previously linked with parturition: IL-8, manganese superoxide dismutase (MnSOD), and metalloproteinase-9. Three others, interferon-inducible 1-8d gene, elongation factor 1alpha, and nucleophosmin, have not been previously linked with labor. Constitutively expressed genes, including cyclophilin and alpha-actin, were found to be altered by labor. Quantitative real-time RT-PCR using Taqman probes further confirmed the up-regulation of some of these genes. The amounts of the specific genes assayed were standardized to 18S ribosomal RNA and are expressed as mean +/- SEM. Quantitative real-time RT-PCR showed that IL-8 mRNA rose from 0.003 +/- 0.002 in nonlaboring s les (n = 38) to 0.24 +/- 0.11 (n = 20) in gestational-age-matched spontaneously laboring women (P = 0.035). Similarly, MnSOD rose from 0.11 +/- 0.02 (n = 24) to 1.23 +/- 0.56 (n = 24) in gestational-age-matched women (P = 0.047). Additionally, cyclophilin, often used as a constitutive or housekeeping gene marker, increased from 0.0008 +/- 0.0002 (n = 6) to 0.002 +/- 0.0004 (n = 6 P = 0.008) during labor. Notably, MnSOD mRNA was differentially distributed between the upper (0.63 +/- 0.18) and lower (0.15 +/- 0.05 n = 15 P = 0.022) segments of the uterus, but IL-8 was not (n = 17 P = 0.97). Induced labor further showed significantly higher levels of IL-8 (0.63 +/- 0.21 n = 14) than spontaneous labor (0.22 +/- 0.11 n = 20 P = 0.046), but not MnSOD (P = 0.1). This work identifies novel as well as known genes that were not previously associated with parturition. It extends previous data indicating that there is differential expression of some, but not all genes within the gravid human uterus. Inflammatory genes constitute a major proportion of the known genes found to be up-regulated in labor, lending support to the hypothesis of an inflammatory mechanism for human parturition. This work further indicates that many factors associated with human labor and their complex interactions remain to be elucidated.
Publisher: CSIRO Publishing
Date: 1991
DOI: 10.1071/RD9910397
Abstract: In vitro release of one of the pro-opiomelanocortin (POMC)-derived peptides, the endogenous opioid beta-endorphin (beta EP) has been examined in the sheep placenta by means of a perifusion system. Two zones of the cotyledon, the chorionic villus (highly vascularized fetal and maternal tissues in close apposition) and the maternal basal plate (or capsule), were examined in placenta at two stages of gestation--120 days (119.0 +/- 4.7, N = 4) and 140 days (143 +/- 1.8, N = 5) just before term. The chorionic villous tissue released more beta EP-like immunoreactivity (beta EP-IR) than did the basal plate tissue at both gestational ages. At 120 days' gestation the basal concentration of beta EP-IR released from the chorionic villus was 52 +/- 0.5 fmol mL-1 (n = 4), almost double the maternal basal plate tissue at 28.4 +/- 0.4 fmol mL-1 (n = 8). beta EP-IR secretory capacity increased significantly (P less than 0.05) with advancing gestational age. By Day 140, release had increased 3-4-fold to 181.8 +/- 0.8 fmol mL-1 (n = 16) in the chorionic villous tissue, and to a lesser extent in the basal plate tissue to 50.7 +/- 0.6 fmol mL-1 (n = 14). No stimulation of beta EP-IR secretion was observed in any tissue as a result of 30 min exposure to corticotrophin-releasing hormone (100 nmol L-1), a vital physiological secretagogue.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: The Endocrine Society
Date: 12-2008
DOI: 10.1210/JC.2008-1077
Abstract: Differential promoter use and alternative splicing generate a variety of glucocorticoid receptor (GR) mRNA transcripts, potentially altering the cortisol responsiveness of gestational tissues during pregnancy and labor. We examined GR mRNA transcript expression in term placentae before and after labor, in association with fetal sex and after glucocorticoid treatment. RNA from 34 placentae and from eight placental explants incubated with glucocorticoids were analyzed for the GR mRNA variants GR-alpha, GR-beta, GR-P, and GR-gamma and the untranslated exon one variants 1A1, 1A2, 1A3, 1B, and 1C by quantitative RT-PCR. mRNA expression was assessed. All GR mRNA variants examined were detected in the human placenta, with GR-alpha and GR-1C mRNA having the highest expression of GR splice variants and exon 1 variants, respectively. GR-P mRNA abundance decreased with spontaneous labor (P < 0.01). GR-1A3 mRNA abundance changed with fetal sex, with a higher level in placentae of male fetuses (P < 0.05). GR-1C was the preferential promoter for GR-alpha, GR-gamma, and GR-P mRNA. GR-beta mRNA was preferentially associated with GR-1A1. GR-P mRNA transcription switched to the GR-1A1 promoter after labor and to the GR-1A3 promoter in placentae from male fetuses. Glucocorticoid treatment significantly reduced transcription from promoters GR-1B and -1C and decreased GR-alpha and GR-P mRNA abundance. The human placenta expresses a variety of GR mRNA transcripts. GR-alpha mRNA transcribed from the 1C promoter generates the majority of placental GR. However, alterations in promoter use and alternative splicing may modulate responses to cortisol during stressful events.
Publisher: Elsevier BV
Date: 02-2022
Publisher: Springer Science and Business Media LLC
Date: 03-1999
Publisher: Cambridge University Press (CUP)
Date: 06-2009
DOI: 10.1017/S1368980008003212
Abstract: To investigate and report the diet quality of young Australian women by pregnancy status. Pregnancy status was defined as pregnant ( n 606), trying to conceive ( n 454), had a baby in the last 12 months ( n 829) and other ( n 5597). The Dietary Questionnaire for Epidemiological Studies was used to calculate diet quality using the Australian Recommended Food Score (ARFS) methodology. Nutrient intakes were compared with the Nutrient Reference Values for Australia and New Zealand. A population-based cohort participating in the Australian Longitudinal Study on Women’s Health (ALSWH). A nationally representative s le of Australian women, aged 25 to 30 years, who completed Survey 3 of the ALSWH. The 7486 women with biologically plausible energy intake estimates, defined as ·5 but ·0 MJ/d, were included in the analyses. Pregnancy status was not significantly predictive of diet quality, before or after adjusting for area of residence and socio-economic status. Pregnant women and those who had given birth in the previous 12 months had marginally higher ARFS (mean ( se ): 30·2 (0·4) and 30·2 (0·3), respectively) than ‘other’ women (29·1 (0·1)). No single food group accounted for this small difference. Across all pregnancy categories there were important nutrients that did not meet the current nationally recommended levels of intake, including dietary folate and fibre. Women do not appear to consume a wider variety of nutritious foods when planning to become pregnant or during pregnancy. Many young Australian women are failing to meet key nutrient targets as nationally recommended.
Publisher: Oxford University Press (OUP)
Date: 27-02-2012
Abstract: Term human myometrial expression of progesterone receptor (PR)-A is increased relative to PR-B, and as PR-A is a repressor of progesterone action mediated through PR-B, this increase may mediate the withdrawal of progesterone action and precipitate the onset of labour. PR-A and PR-B expression is regulated by two separate promoters of the PR gene. We hypothesized that epigenetic histone modifications at the two promoters contribute to the labour-associated regulation of PR-A and PR-B expression in term myometrium. PR total, PR-B and PR-A mRNA levels were determined using quantitative real-time PCR, and chromatin immunoprecipitation was used to determine the levels of activating and repressive histone modifications at the PR-A and PR-B promoters in human myometrial s les not in labour (n = 4) and in labour (n = 4). Chromatin extracts were immunoprecipitated with antibodies against activating (histone H3 and H4 acetylation and histone H3 lysine 4 trimethylation), and repressive (histone H3 lysine 9 trimethylation, histone H3 lysine 27 trimethylation and asymmetrical histone H3 arginine 2 dimethylation) histone modifications. PR-A mRNA levels increased during labour, while PR-B mRNA levels remained constant resulting in an increase of PR-A/PR-B mRNA ratio, as expected. Regardless of labour status, significantly higher levels of the activating histone modifications were found at the PR-A promoter compared with the PR-B promoter (P <0.001). H3K4me3 increased significantly at both promoters with labour onset (P =0.001). Low levels of the repressive histone modifications were also present at both promoters, with no labour-associated changes observed. Our data indicate that the PR-A promoter is epigenetically marked for activation in term myometrium more extensively than the PR-B promoter, and that labour is associated with an increase in H3K4me3 activating modification, consistent with the previously described increase in PR protein at this time.
Publisher: MDPI AG
Date: 20-05-2021
Abstract: Prenatal nutrient exposures can impact on brain development and disease susceptibility across the lifespan. It is well established that maternal macronutrient intake during pregnancy influences foetal and infant development. Therefore, we hypothesise that macronutrient intakes during pregnancy are correlated with cognitive development during early childhood. The current study aimed to investigate the relationship between maternal macronutrient intake during pregnancy and child cognitive and behavioural outcomes at age 4 years. We analysed prospective data from a cohort of 64 Australian mother–child dyads. Maternal macronutrient intake was assessed using a validated 74-item food frequency questionnaire at 2 timepoints during pregnancy. Child cognition and behaviour were measured at age 4 years using the validated Wechsler Preschool and Primary Scale of Intelligence, 3rd version (WPPSI-III) and the Child Behaviour Checklist (CBC). Linear regression models were used to quantify statistical relationships and were adjusted for maternal age, education, pre-pregnancy BMI, breastfeeding duration and birthweight. Child Performance IQ was inversely associated with maternal starch intake (b = −11.02, p = 0.03). However, no other associations were found. Further research is needed to explore the association between different types of starch consumed during pregnancy and child cognitive development.
Publisher: Elsevier BV
Date: 08-1984
DOI: 10.1016/0304-3940(84)90126-5
Abstract: The effect of insulin-induced hypoglycemic stress on the concentrations of immunoreactive beta-endorphin (ir beta-EP) in plasma and cerebrospinal fluid (CSF) was examined in conscious non-pregnant ewes in which the cisterna magna and a jugular vein had been previously catheterized. In control experiments, no significant changes were observed in plasma cortisol or ir beta-EP and CSF ir beta-EP concentrations. During hypoglycemia induced by intravenous injection of 20 units of insulin, plasma cortisol concentrations rose significantly, reaching a peak 1.5 h after injection. The changes in plasma ir beta-EP concentration were significantly different between hypoglycemic and normoglycemic sheep (analysis of variance, P = 0.0089). Following insulin injection, mean plasma ir beta-EP rose by 100% within 0.75 h, continued to rise six-fold over initial concentrations by 2.25 h, and remained elevated for 3.75 h. The CSF ir beta-EP concentrations following insulin injection were not significantly different from those observed in controls. These results suggest that if beta-endorphin mediated hypoglycemic stress-induced analgesia, its actions may be peripheral, not central.
Publisher: Elsevier BV
Date: 11-2001
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1016/J.JAAPOS.2011.03.009
Abstract: The ophthalmological examination of premature infants, which is essential for the detection of retinopathy of prematurity (ROP), can be painful and distressing for the infant. Various researchers have investigated the benefits of topical anesthesia, oral sucrose, and non pharmacological intervention for pain relief. The purpose of this study is to review the current state of knowledge on the effectiveness of these approaches. A literature search was performed with MEDLINE (January 1980 to January 2011) and the Cochrane Central Register of Controlled Trials, Issue 1 of 4 (January 2011), to determine the currently available evidence on methods of pain relief for premature infants undergoing ROP examination. Most studies supported the use of topical proparacaine, which marginally decreased pain without any side effects. Oral sucrose did not significantly reduce pain scores during ROP examinations, and withholding feeding before the examination was not beneficial. Infants given pacifiers had lower pain scores than those without pacifiers, and infants who were nested experienced less distress during and after the procedure. Conflicting data existed on the benefits of different examination techniques, but the insertion of a lid speculum appeared to be the most uncomfortable aspect of the screening examination. Topical anesthetics marginally reduce pain during eye examination in premature infants. Contrary to standard practice, it appears that patients are more comfortable if they are fed before the examination, and there is no benefit of oral sucrose. Nonpharmacological interventions, including sucking on a pacifier and nesting, may also be beneficial.
Publisher: Public Library of Science (PLoS)
Date: 16-09-2021
DOI: 10.1371/JOURNAL.PONE.0257422
Abstract: To determine if maternal plasma CRH and preterm birth history were associated with recurrent preterm birth risk in a high-risk cohort. Secondary analysis of pregnant women with a prior preterm birth ≤35 weeks receiving 17-alpha hydroxyprogesterone caproate for the prevention of recurrent spontaneous preterm birth. All women with a 24-week blood s le were included. Maternal plasma CRH level at 24- and 32-weeks’ gestation was measured using both enzyme-linked immunosorbent assay (ELISA) and extracted radioimmunoassay (RIA) technologies. The primary outcome was spontaneous preterm birth weeks. The association of CRH, prior preterm birth history, and the two combined was assessed in relation to recurrent preterm birth risk. Recurrent preterm birth in this cohort of 169 women was 24.9%. Comparing women who subsequently delivered versus ≥37 weeks, mean levels of CRH measured by RIA were significantly different at 24 weeks (111.1±87.5 vs. 66.1±45.4 pg/mL, P = .002) and 32 weeks (440.9±275.6 vs. 280.2±214.5 pg/mL, P = .003). The area under the receiver operating curve (AUC) at 24 and 32 weeks for (1) CRH level was 0.68 (95% CI 0.59–0.78) and 0.70 (95% CI 0.59–0.81), (2) prior preterm birth history was 0.75 (95% CI 0.67–0.83) and 0.78 (95% CI 0.69–0.87), and (3) combined was 0.81 (95% CI 0.73–0.88, P = .001) and 0.81 (95% CI 0.72–0.90, P = .01) respectively for delivery weeks. CRH measured by ELISA failed to correlate with gestational age or other clinical parameters. In women with a prior preterm birth, CRH levels were higher and had an earlier rise in women who experienced recurrent preterm birth. Second trimester CRH may be useful in identifying a sub-group of women with preterm birth due to early activation of the placenta-fetal adrenal axis. Assay methodology is a variable that contributes to difficulties in reproducibility of CRH levels in the obstetric literature.
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.AJOG.2018.09.038
Abstract: Preventable maternal mortality is related to delays in recognizing the problem, transport to a facility, and receiving appropriate care on arrival. Reducing maternal mortality in low-literacy settings is particularly challenging. In the rural villages of Nepal, the maternal mortality rate is among the highest in the world the reasons include illiteracy and lack of knowledge of the needs of pregnant women. Culturally, singing and dancing are part of Nepalese daily life and present an opportunity to transmit knowledge of antenatal care and care at birth with a view to reducing the first 2 delays. We hypothesized that health messages regarding the importance of antenatal care and skilled birth assistance would be effectively transmitted by songs in the limited literacy environment of rural Nepal. We randomly grouped 4 rural village development committees comprising 36 villages into 2 (intervention and control) clusters. In the intervention group, local groups were invited to write song lyrics incorporating key health messages regarding antenatal care to accompany popular melodies. The groups presented their songs and dances in a festival organized and judged by the community. The winning songs were performed by the local people in a song and dance progression through the villages, houses, and fields. A wall chart with the key health messages was also provided to each household. Knowledge of household decision makers (senior men and women) was assessed before and after the intervention and at 12 months using a structured questionnaire in all households that also assessed behavior change. Structured interviews were conducted at baseline, immediately postintervention in the control and intervention areas (intervention n = 735 interviews, control n = 775), and at 12 months in the intervention area only (n = 867). Knowledge scores were recorded as the number of correct items out of 36 questions at baseline and postintervention, and of 21 questions at follow-up. Postintervention, test score doubled in the intervention group from a mean of 11.60/36-22.33/36 (P < .001), with no practically significant change in the control population (17.48/36-18.26/36). Improvement was greatest among the most illiterate members of the community (6.8/36-19.8/36, P < .001). At 12 months follow-up, a majority of the participants (63.9%) indicated that they provided information learned from the songs to their neighbors and friends, and 41.3% reported still singing the songs from the intervention. The use of songs bypassed the limitations of literacy in communicating health messages that are key to improving maternal care in this low-literacy rural setting within a developing country. The improvements were maintained without further intervention for 12 months. With appropriate sociocultural adaptation to local contexts, this low-cost method of community education may be applicable to improving maternal health knowledge and behavior change in other low-resource and limited literacy settings that may lead to reductions in maternal mortality.
Publisher: Walter de Gruyter GmbH
Date: 2012
DOI: 10.1515/JPM.2011.116
Publisher: The Endocrine Society
Date: 06-2002
Abstract: A number of studies demonstrate that both long-term and short-term exposure to glucocorticoids alters vascular function. We have examined whether the short-term administration of glucocorticoids into the human fetal-placental circulation affects placental arterial pressure and alters vascular responses to vasoconstrictive and vasodilator agents. Single lobules of term human placentae were bilaterally perfused in vitro with Krebs' solution (maternal and fetal, 5 ml/min Krebs, 95% O2, 5% CO2, 37 C, pH 7.3), and changes in fetal-placental arterial perfusion pressure were measured. Dexamethasone (100 nM) infusion for 1 h into the fetal-placental circulation caused a significant decrease in basal arterial pressure (n = 19, t test, P 0.05) or potassium chloride (5-600 mM, n = 12, ANOVA, P > 0.05) or vasodilator responses to CRH (53-7400 pM, n = 13, ANOVA, P > 0.05). However when fetal-placental vessels were submaximally preconstricted and then infused with dexamethasone alone (40 nM-10 microM), there was a dose-dependent decrease in arterial pressure (n = 8). Dexamethasone-induced dilation was not inhibited by blocking nitric oxide synthase or cyclo-oxygenase activity. These data suggest that dexamethasone can cause dilation in the fetal-placental circulation, possibly via an endothelium-independent pathway.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Springer Science and Business Media LLC
Date: 18-01-2013
DOI: 10.1007/S11102-013-0461-9
Abstract: Lymphocytic hypophysitis is an organ-specific autoimmune disease characterised by destruction of pituitary hormone-secreting cells due to attack by self-reactive T lymphocytes. The spectrum of pituitary autoantibodies characterised by indirect immunofluorescence (IF) in these patients has not been substantially defined. The purpose of this study was to determine the spectrum of pituitary autoantibodies in 16 lymphocytic hypophysitis patients. Pituitary sections were prepared from guinea pigs and sera from 16 lymphocytic hypophysitis patients (13 biopsy proven and 3 suspected cases) and 13 healthy controls were evaluated for immunoreactivity to the pituitary tissue by immunofluorescence. A single patient was found to have high titre pituitary autoantibodies against guinea pig pituitary tissue. Immunoreactivity was directed against cells of the intermediate lobe. We present the case report of the patient who is a 24 year old woman that presented with headaches, polyuria and polydipsia. A uniformly enlarged pituitary mass was visible on MRI and a diagnosis of suspected lymphocytic hypophysitis was made. Based on our IF study, we postulate this patient has an autoimmune process directed towards the major cell type in the intermediate lobe, the melanotroph. Pre-adsorption with peptides representing adrenocorticotropic hormone, α-melanocyte stimulating hormone or β-endorphin did not affect the IF signal suggesting our patient's pituitary autoantibodies may target some other product of Proopiomelanocortin (POMC) processing, such as corticotrophin-like intermediate peptide or γ-lipoprotein. Alternatively, the autoantibodies may target a peptide completely unrelated to POMC processing.
Publisher: Elsevier BV
Date: 06-1995
DOI: 10.1016/0301-0511(95)05118-T
Abstract: The relations between three hormones of the hypothalamic-pituitary-adrenocortical (HPA) axis, beta-endorphin (beta-EP), corticotropin-releasing hormone (CRH) and cortisol, and mood change were examined in 11 elite runners and 12 highly trained mediators matched in age, sex, and personality. Despite metabolic differences between running and meditation, we predicted that mood change after these activities would be similar when associated with similar hormonal change. Compared to pre-test and control values, mood was elevated after both activities but not significantly different between the two groups at post-test. There were significant elevations of beta-EP and CRH after running and of CRH after meditation, but no significant differences in CRH increases between groups. CRH was correlated with positive mood changes after running and mediation. Cortisol levels were generally high but erratic in both groups. We conclude that positive affect is associated with plasma CRH immunoreactivity which itself is significantly associated with circulating beta-EP supporting a role for CRH in the release of beta-EP. Increased CRH immunoreactivity following meditation indicates, however, that physical exercise is not an essential requirement for CRH release.
Publisher: Elsevier BV
Date: 06-1988
DOI: 10.1016/S0006-291X(88)81359-7
Abstract: The molecular forms of corticotrophin-releasing hormone (CRH) in human placentae and hypothalami were investigated by gel permeation chromatography of water extracts. Hypothalamic extracts produced one peak of immunoreactivity which coeluted with human CRH at Kd = 0.53. Placental extracts, however, had in addition to that peak, two other peaks eluting earlier at the void and at Kd = 0.35-0.38. Tryptic digestion of the middle peak produced immunoreactivity which coeluted with the standard. Larger forms were also found in plasma of women in the third trimester of pregnancy and during labour but not in eluates from superfused placental fragments which had only CRH41-sized material. These data indicate that tissue-specific post-translational processing occurs for CRH, and suggests that the link between synthesis and secretion is more immediate in the placenta than hypothalamus.
Publisher: Springer Science and Business Media LLC
Date: 22-09-2011
DOI: 10.1038/JP.2011.118
Publisher: Wiley
Date: 1987
DOI: 10.1111/J.1365-2265.1987.TB03645.X
Abstract: The effect of pretreatment with biosynthetic methionyl human GH (hGH) on the GH response to GHRH has been studied in normal subjects. Eight volunteers were given either 4 IU hGH or placebo s.c. 12-hourly for 72 h before a GHRH test, or a single s.c. dose of 4 IU hGH 12 h before a GHRH test. Somatomedin-C (Sm-C) levels at the time of the GHRH tests were significantly elevated after treatment with hGH compared to placebo, and the GH response to GHRH was significantly attenuated. A further six subjects were given 2 IU hGH or placebo i.v., and i.v. GHRH 3 h later there was no rise in Sm-C for the 5 h of the study after either treatment nevertheless, the response to GHRH was completely abolished by pretreatment with hGH. These results demonstrate that GH can regulate its own secretion independently of changes in Sm-C levels, through a mechanism other than the inhibition of GHRH release. The attenuated response to GHRH in the presence of elevated Sm-C levels may be related to Sm-C, or be a more direct effect of the recently elevated GH levels.
Publisher: The Endocrine Society
Date: 08-1999
Abstract: In humans, the length of gestation and the onset of parturition have been linked to the exponential production of placental CRH and a late gestational decline in maternal plasma CRH-binding protein (CRH-BP). CRH has been shown to have direct effects on the myometrium and on the fetal adrenal, where it stimulates production of the estrogen precursor dihydroepiandrosterone sulfate. In vitro placental CRH production is stimulated by cortisol and inhibited by progesterone. To determine whether this mechanism might operate in other apes, we s led eight chimpanzees and two gorillas through their pregnancies for CRH, CRH-BP, cortisol, estradiol, progesterone, and alpha-fetoprotein. We show that both chimpanzee and gorilla maternal plasma CRH concentrations rise exponentially as observed in the human. The gorillas exhibited a human-like antepartum fall in CRH-BP, whereas CRH-BP in the chimpanzee remained stable. Pregnancy-associated changes in cortisol, estradiol, progesterone, and alpha-fetoprotein were qualitatively similar to those observed in humans. Maternal plasma cortisol correlated with plasma CRH in both gorillas (r = 0.60 P < 0.05) and chimpanzees (r = 0.36 P < 0.02). Further, there was a strong correlation between plasma estradiol and the log of plasma CRH in the gorilla (r = 0.93 P < 0.0001) and in the chimpanzee (r = 0.72 P < 0.001), which is consistent with the hypothesis that placental CRH determines the placental production of estradiol by stimulating the production of fetal adrenal dehydroepiandrosterone sulfate. Plasma CRH and progesterone were positively correlated providing no in vivo support for progesterone inhibition of CRH release.
Publisher: Georg Thieme Verlag KG
Date: 10-1988
Abstract: We measured the effect of repeated haemorrhagic stress, performed on four consecutive days in conscious adult sheep, on the plasma concentrations of cortisol and ACTH-related peptides to determine whether the pituitary-adrenal response was altered by stress repetition. Peptides from the C-terminus of the ACTH pro-hormone was measured by beta-endorphin RIA. Glycopeptides derived from the N-terminus of the ACTH pro-hormone were measured by tau 3-MSH RIA. The immunoreactive tau 3-MSH in sheep plasma was found to have an apparent molecular weight of approximately 10,000 by gel chromatography through Sephadex G-75, which is similar to the size of the major circulating form of pro-tau-MSH found in human and rat plasma. Daily haemorrhage consistently elevated plasma concentrations of cortisol and pro-tau-MSH. There was no significant difference in the daily responses of either cortisol or pro-tau-MSH when considered in idually. However, there was a significant change over the four days in the relationship between the cortisol and pro-tau-MSH responses, as judged by analysis of variance of the difference in daily z-scores of cortisol and pro-tau-MSH. This trend indicated a relative increase in the secretion of pro-tau-MSH from the pituitary compared to the cortisol response, and suggested that repeated exposure to stressful stimuli may alter the pituitary-adrenal-axis.
Publisher: MDPI AG
Date: 06-12-2012
DOI: 10.3390/NU4121958
Publisher: Cambridge University Press (CUP)
Date: 31-01-2017
DOI: 10.1017/S2040174416000817
Abstract: Dilation and abnormal tortuosity of retinal vessels are the hallmarks of severe retinopathy of prematurity (ROP) in premature infants. The stages of ROP are defined by vessel appearance at the interface between the vascular and avascular retinal areas. Deregulated signaling pathways involving hypoxia-inducible factors such as vascular endothelial growth factor (VEGF) are involved in the pathogenesis of ROP. VEGF-antagonists are increasingly being used as ‘off-label medication’ to treat this condition, with some success. We present Baby SM (female), who was born prematurely at 24 weeks gestation in a tertiary neonatal intensive care unit, and with a birth weight of 640 g. On screening at 35 weeks postmenstrual age (PMA), she was noted to have ROP, which became severe by 37 weeks PMA. She received one dose of intravitreal VEGF antagonist (Bevacizumab), resulting in a decrease in vessel tortuosity and dilation. However, repeat imaging at 4 weeks showed a re-emergence of vessel tortuosity. We believe the observed changes demonstrate an inherent retinal microvascular plasticity in premature neonates. With improved survival of extremely premature neonates and the availability of retinal imaging technology, we are now able to observe this plasticity.
Publisher: Elsevier BV
Date: 2017
DOI: 10.4158/EP15785.CR
Publisher: Public Library of Science (PLoS)
Date: 13-09-2019
Publisher: Massachusetts Medical Society
Date: 18-01-2007
DOI: 10.1056/NEJMRA061360
Publisher: Frontiers Media SA
Date: 16-06-2015
Publisher: AMPCo
Date: 08-1995
DOI: 10.5694/J.1326-5377.1995.TB127971.X
Abstract: The purpose of the current study is to translate, test and evaluate the psychometric properties of the Glasgow Sleep Effort Scale (GSES) in Persian language. Participants consisted of two s les: a clinical s le of 120 patients (58%) with insomnia disorder meeting DSM-5 criteria for insomnia and a non-clinical s le of 110 participants (42%) with normal sleep. Both s les completed the following measures: GSES, Pittsburg Sleep Quality Index, Insomnia Severity Index, Dysfunctional Beliefs and Attitudes about Sleep Scale-10, Pre Sleep Arousal Scale-cognitive subscale, Depression-Anxiety-Stress Scale-21 and sleep diary. Significant correlations were found between GSES and related measures in both groups. Principal component analysis indicated a single component accounted for 64.77% of total variance in the clinical group. Results of the fit estimates for the one-factor model were consistent with the previously specified fit criteria and adequately fitted the data in the non-clinical group. Statistical analyses showed that the GSES has acceptable internal consistency in terms of Cronbach's Alpha in the clinical (0.75) and non-clinical (0.77) s les. Test-retest reliability for a 4-week interval was significant (r = 0.70). The cut-off point, sensitivity, and specificity of the scale were 6, 85% and 94.5%, respectively. The Persian translated and validated version of the GSES obtained adequate values in psychometric properties in both clinical and non-clinical s les and it can be used for research and clinical purposes in Iran.
Publisher: The Endocrine Society
Date: 04-2012
DOI: 10.1210/EN.2012-1010
Publisher: The American Association of Immunologists
Date: 02-2009
DOI: 10.4049/JIMMUNOL.182.3.1411
Abstract: In the presence of maternal asthma, we have previously reported reduced placental blood flow, decreased cortisol metabolism, and reductions in fetal growth in response to maternal asthma and asthma exacerbations. We have proposed that these changes in placental function and fetal development may be related to activation of proinflammatory pathways in the placenta in response to maternal asthma. In the present study, we examined the influence of maternal asthma severity, inhaled glucocorticoid treatment, maternal cigarette use, placental macrophage numbers, and fetal sex on placental cytokine mRNA expression from a prospective cohort study of pregnant women with and without asthma. Placental expression of TNF-α, IL-1β, IL-6, IL-8, and IL-5 mRNA were all increased significantly in placentae of female fetuses whose mothers had mild asthma, but no changes were observed in placentae of male fetuses. The proinflammatory cytokines TNF-α, IL-1β, and IL-6 were negatively correlated with female cord blood cortisol, but there were no such correlations in placentae from males. Multivariate analysis indicated the strongest predictor of both cytokine mRNA expression in the placenta and birth weight was fetal cortisol but only in females. Placental cytokine mRNA levels were not significantly altered by inhaled glucocorticoid use, placental macrophage numbers, cigarette use, moderate-severe asthma, or male sex. These data suggest that placental basal cytokine mRNA expression is sex specifically regulated in pregnancies complicated by asthma, and interestingly these changes are more prevalent in mild rather than severe asthma.
Publisher: Oxford University Press (OUP)
Date: 10-2018
Publisher: The Endocrine Society
Date: 04-2006
DOI: 10.1210/ER.2005-0011
Abstract: The environment in which the fetus develops is critical for its survival and long-term health. The regulation of normal human fetal growth involves many multidirectional interactions between the mother, placenta, and fetus. The mother supplies nutrients and oxygen to the fetus via the placenta. The fetus influences the provision of maternal nutrients via the placental production of hormones that regulate maternal metabolism. The placenta is the site of exchange between mother and fetus and regulates fetal growth via the production and metabolism of growth-regulating hormones such as IGFs and glucocorticoids. Adequate trophoblast invasion in early pregnancy and increased uteroplacental blood flow ensure sufficient growth of the uterus, placenta, and fetus. The placenta may respond to fetal endocrine signals to increase transport of maternal nutrients by growth of the placenta, by activation of transport systems, and by production of placental hormones to influence maternal physiology and even behavior. There are consequences of poor fetal growth both in the short term and long term, in the form of increased mortality and morbidity. Endocrine regulation of fetal growth involves interactions between the mother, placenta, and fetus, and these effects may program long-term physiology.
Publisher: CSIRO Publishing
Date: 1991
DOI: 10.1071/RD9910379
Abstract: This study has utilized a tissue perifusion system to examine the release of insulin-like growth factor I (IGF I) from different regions of the sheep placenta at two stages of gestation. Placentae were obtained from ewes at either 116 +/- 7 (mean +/- s.e.) or 144 +/- 1.5 days of gestation and separated into the maternal basal plate or chorionic villous tissue. At both ages, the maternal basal plate tissue released approximately three times more IGF I than the chorionic villous tissue. No difference was found between the rate of release of IGF I from the maternal basal plate at 120 and 140 days of gestation, whereas the chorionic villous tissue released less IGF I later in gestation. Maternal basal plate tissue was less responsive to a depolarizing dose of KCl than was chorionic villous tissue at either age. After acid gel chromatography, perfusate from the basal plate had three peaks of IGF immunoreactivity (corresponding to binding protein, IGF I and a form with an intermediate molecular weight). In contrast, the chorionic villous tissue released only a form with a high molecular weight, corresponding to binding protein. These results demonstrate that the sheep placenta produced IGF I, that secretion varies between different placental zones which contain different cell types and that there are maturational changes in placental IGF I secretion. The IGFs may be involved in placental growth.
Publisher: MDPI AG
Date: 28-10-2015
DOI: 10.3390/SYM7041981
Publisher: Elsevier BV
Date: 04-2002
DOI: 10.1016/S0021-9673(02)00196-6
Abstract: Retention and separation studies of selected estrogens, progestogens and their inclusion complexes with beta-cyclodextrin were conducted using two C18 HPLC columns with different carbon loads. The difference in carbon load between investigated octadecylsilica packing materials was about 50%. The mobile phases were composed of a 30% v/v acetonitrile-water mixture without and with addition of beta-cyclodextrin at a concentration of 12 mM. The experimental data revealed that retention of the steroids was significantly reduced on the column with the lower carbon load. Moreover, it was found that this column offers better separation power and shorter analysis time at the temperatures studied. However, the calculated values of the retention factor ratios (k0(mMCD))/k(12mMCD)) of the steroids were similar for both columns investigated. This observation suggests that the stationary phase structure appears to have little effect on the formation of host-guest complexes if the complexation process is localised to the chromatographic mobile phase. From a practical point of view, when the mobile phase is modified with beta-cyclodextrin, the separation of the steroids is strongly influenced by temperature. The best chromatographic conditions were determined for the separation of multicomponent s les on the column with lower carbon load. A possible retention mechanism for components of interest in the presence of macrocyclic additives is discussed.
Publisher: American Physiological Society
Date: 07-2002
DOI: 10.1152/AJPENDO.00497.2001
Abstract: We hypothesized that urocortin might be produced in the pituitary of the late-gestation ovine fetus in a manner that could contribute to the regulation of ACTH output. We used in situ hybridization and immunohistochemistry to identify urocortin mRNA and protein in late-gestation fetal pituitary tissue. Levels of urocortin mRNA rose during late gestation and were associated temporally with rising concentrations of pituitary proopiomelanocortin (POMC) mRNA. Urocortin was localized both to cells expressing ACTH and to non-ACTH cells by use of dual immunofluorescence histochemistry. Transfection of pituitary cultures with urocortin antisense probe reduced ACTH output, whereas added urocortin stimulated ACTH output from cultured pituitary cells. Cortisol infusion for 96 h in chronically catheterized late-gestation fetal sheep significantly stimulated levels of pituitary urocortin mRNA. We conclude that urocortin is expressed in the ovine fetal pituitary and localizes with, and can stimulate output of, ACTH. Regulation of urocortin by cortisol suggests a mechanism to override negative feedback and sustain feedforward of fetal hypothalamic-pituitary-adrenal function, leading to birth.
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.EJMECH.2019.111948
Abstract: The aldehyde oxidases (AOXs) are a small sub-family of cytosolic molybdo-flavoenzymes, which are structurally conserved proteins and broadly distributed from plants to animals. AOXs play multiple roles in both physiological and pathological processes and AOX inhibition is of increasing significance in the development of novel drugs and therapeutic strategies. This review provides an overview of the evolution and the action mechanism of AOX and the role of each domain. The review provides an update of the polymorphisms in the human AOX. This review also summarises the physiology of AOX in different organs and its role in drug metabolism. The inhibition of AOX is a promising therapeutic treatment for cancer, obesity, aging and amyotrophic lateral sclerosis.
Publisher: Elsevier BV
Date: 05-2019
Publisher: Wiley
Date: 27-11-2018
DOI: 10.1111/NEP.13520
Publisher: Bioscientifica
Date: 06-2017
DOI: 10.1530/ERC-17-0010
Abstract: Recent advances in the arena of theranostics have necessitated a re-examining of previously established fields. The existing paradigm of therapeutic thyroid-stimulating hormone receptor (TSHR) targeting in the post-surgical management of differentiated thyroid cancer using levothyroxine and recombinant human thyroid-stimulating hormone (TSH) is well understood. However, in an era of personalized medicine, and with an increasing awareness of the risk profile of longstanding pharmacological hyperthyroidism, it is imperative clinicians understand the molecular basis and magnitude of benefit for in idual patients. Furthermore, TSHR has been recently re-conceived as a selective target for residual metastatic thyroid cancer, with pilot data demonstrating effective targeting of nanoparticles to thyroid cancers using this receptor as a target. This review examines the evidence for TSHR signaling as an oncogenic pathway and assesses the evidence for ongoing TSHR expression in thyroid cancer metastases. Priorities for further research are highlighted.
Publisher: Elsevier BV
Date: 11-2001
DOI: 10.1016/S0196-9781(01)00486-7
Abstract: Corticotrophin-releasing hormone (CRH) is a 41 amino acid neuropeptide that is expressed in the hypothalamus and the human placenta. Placental CRH production has been linked to the determination of gestational length in the human. Although encoded by a single copy gene, CRH expression in the placenta is regulated differently to the hypothalamus. Glucocorticoids stimulate CRH promoter activity in the placenta but inhibit it's activity in the hypothalamus, via mechanisms involving different regions of the CRH promoter. We discuss how various stimuli alter CRH promoter activity and why these responses are unique to the placenta.
Publisher: Elsevier BV
Date: 08-2006
DOI: 10.1016/J.PLACENTA.2005.08.007
Abstract: Studies have shown that pregnancy can alter the pathophysiology of a pre-existing maternal disease such as asthma. However, the mechanisms that alter maternal asthma during pregnancy are presently unknown. Previous work has demonstrated that human bronchial smooth muscle (BSM) cells produce inflammatory factors in response to nonpregnant, atopic plasma. The aim of this study was to determine whether circulating pregnancy-derived factors in maternal and fetal plasma can stimulate inflammatory mediator release in BSM cells in the presence and absence of maternal asthma. Cultured human BSM cells were exposed to maternal and fetal plasma from normal pregnancies and pregnancies complicated by asthma. Inflammatory mediator release was determined by enzyme-linked immunosorbent assay (ELISA). Both maternal and fetal plasma from asthmatic and nonasthmatic in iduals significantly increased production of interleukin (IL)-6 (ANOVA, P<0.001), regulated upon activation, normal T-cell expressed and secreted (RANTES) (ANOVA, P<0.01), and soluble intercellular cell-adhesion molecule-1 (sICAM-1) (ANOVA, P<0.01). There was no difference in inflammatory mediator release in response to asthma and nonasthmatic plasma. Eotaxin release was increased by pregnant asthmatic plasma (ANOVA, P<0.05). The results of this study suggest that circulating pregnancy-related factors can activate asthma-associated mediators in BSM cells. This change in BSM function may be one mechanism that contributes to increased asthma severity during pregnancy.
Publisher: Informa UK Limited
Date: 20-06-2018
DOI: 10.1080/14767058.2017.1338261
Abstract: The objective of this study was to investigate the association between prematurity, vascular endothelial growth factor A (VEGF-A), VEGFR-1 (soluble fms-like tyrosine kinase-1 (sFLT-1)) and retinopathy of prematurity (ROP). A cohort of 53 neonates (gestation <28 weeks) was recruited into this study and peripheral venous s les for VEGF and sFLT-1 measurement were obtained between gestational ages 32 The mean birth weight for the preterm neonates was 850 (178) g and the median gestational age was 26.4 [24.7-27.4] weeks. The median VEGF-A level was 1348 [608-2216] pg/mL and the median sFLT-1 level was 178 [103-244] pg/mL. Thirty-three neonates (33/53) developed various stages of ROP during their stay in the neonatal unit but only five neonates developed severe (stage 3) ROP needing treatment. The neonates with ROP were smaller (birth weight 801 (111) vs. 990 (175) g p < .0001), more preterm (gestation 25.4 [24.2-26.0] vs. 27.1 [26.8-27.9] weeks p < .0001) and received supplemental oxygen for a longer duration (1140 [218-1813] vs. 04 [40-434] hours p= .012). There was no statistically significant difference in the VEGF-A level or sFLT-1 levels between those who developed ROP and those who did not. There was a positive correlation between VEGF and both birth weight and gestation, respectively. There was no correlation between sFLT1 and birth weight or gestation. VEGF-A/sFLT-1 ratio in babies treated for ROP was significantly lower compared to those not treated (2.8 [1.0-5.7] vs. 9.9 [5.6-13.7] p = .04). A logistic regression model identified gestational age to be a statistically significant predictor of ROP (odds ratio 0.03 (0.001-0.550) p = .019). There is no direct correlation between systemic VEGF-A or sFLT-1 plasma levels and severity of ROP in extremely preterm neonates. The link between VEGF and ROP remains to be fully understood.
Publisher: MDPI AG
Date: 20-11-2017
DOI: 10.3390/NU9111265
Publisher: Elsevier BV
Date: 11-2012
DOI: 10.1016/J.PLACENTA.2012.08.004
Abstract: To examine whether syncytin-1 has immune regulatory functions and is carried by human placental exosomes. Further, to examine whether corticotropin-releasing hormone (CRH) can induce the production of syncytin-1. Human placental exosomes were isolated from placental explant, primary trophoblast and BeWo cell cultures. The presence of exosomes was confirmed by transmission electron microscopy and western blotting. Exosomal protein was probed with 3 separate antibodies targeting syncytin-1. Syncytin-1 immunosuppression was tested, using either a syncytin-1 recombinant ectodomain protein or a synthetic peptide with the human syncytin-1 immunosuppressive domain sequence, in an in vitro human blood culture system immune challenged with LPS or PHA. The inhibition of cytokine production by syncytin-1 was determined by ELISA of TNF-α, IFN-γ and CXCL10. BeWo cells were stimulated with CRH or vehicle for 24 h. mRNA and Protein was extracted from the cells for real-time PCR and western blotting analysis while exosomes were extracted from conditioned media for analysis by western blotting. Protein expression of syncytin-1 was detected in exosomes isolated from placental explants, primary trophoblast and BeWo cell cultures. Syncytin-1 recombinant ectodomain was also shown to inhibit the production of the Th1 cytokines TNF-α and IFN-γ as well as the chemokine, CXCL10 in human blood cells. Finally, this study showed that syncytin-1 can be stimulated by CRH. The presence of syncytin-1 in placental exosomes provides a mechanism for syncytin-1 to reach and interact with target cells of the maternal immune system and represents a novel mechanism of endogenous retroviral mediated immunosuppression that may be relevant for maternal immune tolerance.
Publisher: Elsevier BV
Date: 09-2008
Publisher: Springer Science and Business Media LLC
Date: 23-11-2014
Publisher: The Endocrine Society
Date: 1979
Abstract: Daily administration of 5microgram of D-Ser(TBU)6-LH-RH-EA10 for one week produced a significant increase in the LH response to GnRH in hypogonadotropic hypogonadal subjects and a significant decrease in the response of normal male adults. Basal plasma testosterone concentrations fell in normal controls but were unchanged in the hypogonadal group.
Publisher: Wiley
Date: 02-2006
DOI: 10.1002/AJP.20215
Abstract: Corticotropin-releasing hormone (CRH), a potent neuropeptide, is produced by the placenta of anthropoid primates. No other mammals, including prosimian primates, are known to produce placental CRH. In humans, placental CRH appears to play an important role in the progression of pregnancy to parturition. Maternal circulating CRH begins to rise early in pregnancy and increases until parturition. Gorillas and chimpanzees share this pattern of increasing maternal CRH during pregnancy with humans. In humans, chimpanzees, and gorillas, maternal CRH and estradiol concentrations are correlated, consistent with the hypothesis that CRH is involved in the biosynthetic pathway for placental estrogen production. In contrast, in baboons, maternal circulating CRH rises precipitously early in pregnancy and then declines, though CRH is detectable until birth. This research was designed to investigate the pattern of maternal circulating CRH in the common marmoset during pregnancy. Blood s les were taken across gestation from nine subjects over 11 pregnancies, and the plasma was assayed for CRH. The pattern of maternal circulating CRH in the common marmoset was similar to that of the baboon, with a rapid rise starting at about 50 days postconception and a peak at approximately 70 days postconception. By 110 days postconception, CRH concentration had plateaued at a significantly lower value. The peak and mean values for CRH were associated with fetal number (e.g., females gestating triplets had higher values than females gestating twins). Urinary estradiol showed no association with plasma CRH concentration. Marmosets appear to differ from the great apes in this regard, and to share a pattern of maternal CRH during pregnancy with the baboon, indicating that the baboon and marmoset pattern may be ancestral. The function of the early rapid rise of CRH in baboons and marmosets, and the significance of this difference between monkeys and apes, are not known.
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/J.PLACENTA.2005.12.010
Abstract: Pregnant women with asthma are frequently exposed to synthetic glucocorticoids and glucocorticoids are known to reduce fetal growth. The fetus is normally protected from the harmful effects of maternally derived glucocorticoids by the placental enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2). Whether 11beta-HSD2 inactivates the synthetic glucocorticoids used for asthma treatment during pregnancy (budesonide, beclomethasone dipropionate and fluticasone propionate) remains unknown. To investigate the relationship between steroid use during pregnancy and fetal growth and development, pregnant women with (n=119) and without asthma (n=84) were followed throughout pregnancy. Data on asthma medication use, neonatal size at birth, placental weight and cord blood cortisol and estriol were collected. Placental tissue s les were collected from non-asthmatic women (n=8) for metabolism studies. Placental 11beta-HSD2 activity was determined using beclomethasone dipropionate, budesonide, fluticasone propionate, prednisolone, dexamethasone and betamethasone as steroid substrates. Steroids and their oxidised metabolites were examined using thin layer chromatography and densitometry. Placental 11beta-HSD2 metabolised beclomethasone, prednisolone, dexamethasone and betamethasone, but not budesonide or fluticasone. No association between the use of inhaled steroids for asthma treatment during pregnancy and alterations in neonatal size, placental weight, gestational age at delivery, or umbilical vein estriol concentrations was demonstrated compared to non-asthmatic women. In conclusion, the use of inhaled steroids for asthma treatment does not affect fetal growth, despite differences in placental metabolism by 11beta-HSD2.
Publisher: Elsevier BV
Date: 03-2001
DOI: 10.1016/S0021-9673(01)00561-1
Abstract: The influence of temperature on retention and separation of estrogens, progesterone derivatives and beta-cyclodextrin in reversed-phase high-performance liquid chromatography has been studied. Steroids were detected using direct UV detection at 240 and 280 nm. Detection of beta-cyclodextrin was achieved using a post-column indirect photometric method. Chromatographic experiments were performed using an acetonitrile-water mobile phase (30%, v/v) and a wide range of column temperatures from 0 to 80 degrees C with 20 degrees C steps. Linear Van't Hoff plots were observed for steroids and beta-cyclodextrin when an unmodified binary mobile phase was applied. The retention of steroids was strongly influenced by temperature when the mobile phase was modified with beta-cyclodextrin at a concentration of 12 mM. Particularly, for 17beta-estradiol and 20alpha-hydroxyprogesterone a strong deviation from the linear Van't Hoff plots and a remarkable affinity for beta-cyclodextrin was observed. Polynomial regression calculations were performed to fit the set of experimental data points. Using third-order polynomial equations, minimum separation factor values (alphamin) were calculated for temperatures from -10 to + 100 degrees C with 1 degrees C steps. The best chromatographic conditions for separation of multicomponent s les were chosen. A possible retention mechanism for solutes in the presence of macrocyclic additives is discussed. The results presented describe the role of temperature in high-performance liquid chromatography systems in which the mobile phase is modified with an inclusion agent.
Publisher: Annual Reviews
Date: 23-11-2013
DOI: 10.1146/ANNUREV-GENET-111212-133258
Abstract: Understanding genetic variation of complex traits in human populations has moved from the quantification of the resemblance between close relatives to the dissection of genetic variation into the contributions of in idual genomic loci. However, major questions remain unanswered: How much phenotypic variation is genetic how much of the genetic variation is additive and can be explained by fitting all genetic variants simultaneously in one model, and what is the joint distribution of effect size and allele frequency at causal variants? We review and compare three whole-genome analysis methods that use mixed linear models (MLMs) to estimate genetic variation. In all methods, genetic variation is estimated from the relationship between close or distant relatives on the basis of pedigree information and/or single nucleotide polymorphisms (SNPs). We discuss theory, estimation procedures, bias, and precision of each method and review recent advances in the dissection of genetic variation of complex traits in human populations. By using genome-wide data, it is now established that SNPs in total account for far more of the genetic variation than the statistically highly significant SNPs that have been detected in genome-wide association studies. All SNPs together, however, do not account for all of the genetic variance estimated by pedigree-based methods. We explain possible reasons for this remaining “missing heritability.”
Publisher: The Endocrine Society
Date: 12-1997
Publisher: Elsevier BV
Date: 11-2000
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2013
Publisher: The Endocrine Society
Date: 06-2000
Abstract: Heme oxygenase (HO) catalyses the formation of endogenous carbon monoxide and bilirubin from heme. CO, a potent vasodilator, and bilirubin, an antioxidant may have local actions in the fetal-placental vasculature of the placenta. We sought evidence of expression of the two known isoforms of HO in normal human term placenta using reverse transcription polymerase chain reaction (RT-PCR), western blotting and immunohistochemistry. RT-PCR demonstrated the presence of messenger ribonucleic acid for HO-1 and HO-2. Immunoreactive proteins of appropriate size for each HO enzyme were identified in placental cell membrane preparations. Immunohistochemistry showed a wide distribution of HO immunoreactivity, including the syncytiotrophoblast layer of placental villi, the endothelium and smooth muscle cells of umbilical-placental blood vessels, and in all layers of the fetal membranes. These data demonstrate the expression of the two known isoforms of HO in human placenta and suggest that endogenous CO and bilirubin may have important roles in the control of placental vascular function.
Publisher: Springer Science and Business Media LLC
Date: 04-04-2013
Publisher: European Respiratory Society (ERS)
Date: 04-2005
DOI: 10.1183/09031936.05.00085704
Abstract: Asthma is becoming increasingly prevalent worldwide. Numerous historical and prospective cohort studies have investigated the effects of maternal asthma on pregnancy outcome however, the data has been conflicting and many studies have not used standard classifications for asthma severity. Overall, the literature suggests that asthmatic females are more at risk of low birth weight neonates, pre-term delivery and complications such as pre-ecl sia, especially in the absence of actively managed asthma treated with inhaled corticosteroids. Pregnancy with a female foetus may particularly increase the risk of these outcomes. In addition, pregnancy has an effect on the course of asthma. The risk of an exacerbation requiring medical intervention may be as high as 50% in females with severe asthma and this may further increase the risk of poor outcomes, particularly low birth weight and pre-term delivery. The mechanisms responsible for changes in asthma with pregnancy, or alterations in pregnancy outcomes due to asthma have not been thoroughly explored. Maternal inflammatory pathways may contribute to reduced foetal growth through alterations in placental function. Asthma treatment, by reducing maternal inflammation and preventing exacerbations, is safe for use in pregnant females and contributes to improved outcomes for both mother and foetus.
Publisher: Oxford University Press (OUP)
Date: 19-02-2016
DOI: 10.1093/MNRAS/STW395
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.AJOG.2017.06.015
Abstract: The risk of unexplained fetal death or stillbirth increases late in pregnancy, suggesting that placental aging is an etiological factor. Aging is associated with oxidative damage to DNA, RNA, and lipids. We hypothesized that placentas at >41 completed weeks of gestation (late-term) would show changes consistent with aging that would also be present in placentas associated with stillbirths. We sought to determine whether placentas from late-term pregnancies and unexplained stillbirth show oxidative damage and other biochemical signs of aging. We also aimed to develop an in vitro term placental explant culture model to test the aging pathways. We collected placentas from women at 37-39 weeks' gestation (early-term and term), late-term, and with unexplained stillbirth. We used immunohistochemistry to compare the 3 groups for: DNA/RNA oxidation (8-hydroxy-deoxyguanosine), lysosomal distribution (lysosome-associated membrane protein 2), lipid oxidation (4-hydroxynonenal), and autophagosome size (microtubule-associated proteins 1A/1B light chain 3B, LC3B). The expression of aldehyde oxidase 1 was measured by real-time polymerase chain reaction. Using a placental explant culture model, we tested the hypothesis that aldehyde oxidase 1 mediates oxidative damage to lipids in the placenta. Placentas from late-term pregnancies show increased aldehyde oxidase 1 expression, oxidation of DNA/RNA and lipid, perinuclear location of lysosomes, and larger autophagosomes compared to placentas from women delivered at 37-39 weeks. Stillbirth-associated placentas showed similar changes in oxidation of DNA/RNA and lipid, lysosomal location, and autophagosome size to placentas from late-term. Placental explants from term deliveries cultured in serum-free medium also showed evidence of oxidation of lipid, perinuclear lysosomes, and larger autophagosomes, changes that were blocked by the G-protein-coupled estrogen receptor 1 agonist G1, while the oxidation of lipid was blocked by the aldehyde oxidase 1 inhibitor raloxifene. Our data are consistent with a role for aldehyde oxidase 1 and G-protein-coupled estrogen receptor 1 in mediating aging of the placenta that may contribute to stillbirth. The placenta is a tractable model of aging in human tissue.
Publisher: MDPI AG
Date: 25-11-2019
DOI: 10.3390/IJMS20235924
Abstract: Metastases in thyroid cancer are associated with aggressive disease and increased patient morbidity, but the factors driving metastatic progression are unclear. The precursor for nerve growth factor (proNGF) is increased in primary thyroid cancers, but its expression or significance in metastases is not known. In this study, we analysed the expression of proNGF in a retrospective cohort of thyroid cancer lymph node metastases (n = 56), linked with corresponding primary tumours, by automated immunohistochemistry and digital quantification. Potential associations of proNGF immunostaining with clinical and pathological parameters were investigated. ProNGF staining intensity (defined by the median h-score) was significantly higher in lymph node metastases (h-score 94, interquartile range (IQR) 50–147) than in corresponding primary tumours (57, IQR 42–84) (p = 0.002). There was a correlation between proNGF expression in primary tumours and corresponding metastases, where there was a 0.68 (95% CI 0 to 1.2) increase in metastatic tumour h-score for each unit increase in the primary tumour h-score. However, larger tumours (both primary and metastatic) had lower proNGF expression. In a multivariate model, proNGF expression in nodal metastases was negatively correlated with lateral neck disease and being male. In conclusion, ProNGF is expressed in locoregional metastases of thyroid cancer and is higher in lymph node metastases than in primary tumours, but is not associated with high-risk clinical features.
Publisher: Public Library of Science (PLoS)
Date: 04-12-2014
Publisher: Wiley
Date: 04-1992
DOI: 10.1111/J.1651-2227.1992.TB12235.X
Abstract: Seven children were diagnosed as having an emotional cause for growth failure. Pretreatment growth hormone secretion profiles during sleep were analysed using PULSAR. Mean (+/- SD) growth hormone concentration was 10.9 (4.4) mU/l, mean peak 19.6 (6.7) mU/l and the peak-to-peak interval 147 (108) min. Mean (SEM) IGF-I was 1.08 (0.31). The seven children received a six-month course of recombinant growth hormone in a double-blind, crossover study using a dose of 1.2 U/kg/week (28 U/m2/week). Daily placebo injections were given for the other six-month epoch, with a one month washout period. The mean (SEM) growth velocity SD score after growth hormone administration was +4.66 (1.88) and after placebo -0.60 (0.69), each value being greater than the pretreatment value of -2.32 (0.122) (p less than 0.0001 on analysis of variance). The change in IGF-I during growth hormone treatment was not significant. No significant changes in food energy or protein intake occurred.
Publisher: Elsevier BV
Date: 10-2020
DOI: 10.1016/J.GHIR.2009.07.004
Abstract: Fetal growth varies in a sex-specific manner in response to maternal asthma during pregnancy, but the mechanisms are unclear. We examined the influence of maternal asthma severity and associated exposures, inhaled glucocorticoid treatment, maternal cigarette use, and fetal sex on fetal growth and placental function during pregnancy and on the newborn insulin-like growth factor (IGF) axis. STUDY SUBJECTS AND DESIGN: Fetal growth was assessed in a prospective cohort of asthmatic and non-asthmatic women (n=145). At delivery, umbilical vein plasma was collected from male (n=61, controls n=16 and asthmatic n=45) or female (n=84, controls n=22 and asthmatic n=62) fetuses. Cord plasma insulin-like growth factor (IGF) binding protein (BP)-1, IGFBP-3, IGF-1 and IGF-2 were measured by radioimmunoassay and ELISA. Cord plasma IGF-1 was the main component of the neonatal IGF axis altered by asthma and cigarette use. IGF-1 was increased in the presence of mild asthma and a male fetus and decreased in the presence of a female fetus and maternal asthma with cigarette use. IGFBP-3 was also decreased in the female fetuses of pregnancies complicated by asthma and cigarette use. Inhaled glucocorticoid use for the treatment of asthma did not affect the IGF axis. The strongest overall predictor of female birth weight after accounting for asthma severity, inhaled glucocorticoid treatment and cigarette use was IGF-1. For males, the strongest predictor of birth weight was IGFBP-3. The data suggest male and female fetuses institute different strategies in response to adverse pregnancy conditions such as asthma and cigarette use.
Publisher: Wiley
Date: 18-06-2016
Publisher: The Endocrine Society
Date: 08-12-2022
Abstract: Preterm birth worldwide remains a significant cause of neonatal morbidity and mortality, yet the exact mechanisms of preterm parturition remain unclear. Preterm birth is not a single condition, but rather a syndrome with a multifactorial etiology. This multifactorial nature explains why in idual predictive measures for preterm birth have had limited sensitivity and specificity. One proposed pathway for preterm birth is via placentally synthesized corticotrophin-releasing hormone (CRH). CRH is a peptide hormone that increases exponentially in pregnancy and has been implicated in preterm birth because of its endocrine, autocrine, and paracrine roles. CRH has actions that increase placental production of estriol and of the transcription factor nuclear factor-κB, that likely play a key role in activating the myometrium. CRH has been proposed as part of a placental clock, with early activation of placental production resulting in preterm birth. This article will review the current understanding of preterm birth, CRH as an initiator of human parturition, and the evidence regarding the use of CRH in the prediction of preterm birth.
Publisher: The Endocrine Society
Date: 05-2004
Abstract: Placental CRH plays a major role in the mechanisms controlling human pregnancy and parturition. Understanding how placental CRH production is regulated is therefore of importance. Previously we have shown that placental expression of CRH peptide and mRNA are inhibited by estrogens, in contrast to the stimulatory effects of estrogen on hypothalamic CRH production. Our current study found that in placental cells cotransfected with a CRH promoter construct and an estrogen receptor-alpha expression vector results in a differential regulation whereby 17beta-estradiol (E2) decreased and the putative pure estrogen antagonist, ICI 182780, increased CRH promoter activity. Sequential deletion of the CRH promoter indicated that the region between -248 and -213 bp was essential for the effect of both E2 and ICI 182780. This region contains a consensus cAMP regulatory element (CRE) that is a requirement for E2- and ICI 182780-mediated activity because the CRE motif can confer E2 inhibition on a heterologous promoter such as rabbit beta-globin. Mutation of the CRE resulted in a complete reversal of E2 and ICI 182780 regulatory effects. In summary, our results demonstrate that a consensus CRE is required for the action of estrogen receptor ligands in human placental syncytiotrophoblast cells.
Publisher: Frontiers Media SA
Date: 09-01-2018
Publisher: Elsevier
Date: 2011
Publisher: The Endocrine Society
Date: 02-1996
DOI: 10.1210/JC.81.2.763
Publisher: Frontiers Media SA
Date: 11-11-2022
DOI: 10.3389/FENDO.2022.1011689
Abstract: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous endocrine-disrupting combustion by-products that have been linked to preterm birth. One possible mechanism is through disruption of placental corticotropin releasing hormone (pCRH), a key hormone implicated in parturition. As an extension of recent research identifying pCRH as a potential target of endocrine disruption, we examined maternal PAH exposure in relation to pCRH in a large, erse s le. Participants, drawn from the CANDLE cohort, part of the ECHO-PATHWAYS Consortium, completed study visits at 16-29 weeks (V1) and 22-39 weeks (V2) gestation (n=812). Seven urinary mono-hydroxylated PAH metabolites (OH-PAHs) were measured at V1 and serum pCRH at V1 and V2. Associations between in idual log-transformed OH-PAHs (as well as two summed PAH measures) and log(pCRH) concentrations across visits were estimated using mixed effects models. Minimally-adjusted models included gestational age and urinary specific gravity, while fully-adjusted models also included sociodemographic characteristics. We additionally evaluated effect modification by pregnancy complications, fetal sex, and maternal childhood trauma history. We observed associations between 2-OH-Phenanthrene (2-OH-PHEN) and rate of pCRH change that persisted in fully adjusted models (β=0.0009, 0.00006, 0.0017), however, positive associations with other metabolites (most notably 3-OH-Phenanthrene and 1-Hydroxypyrene) were attenuated after adjustment for sociodemographic characteristics. Associations tended to be stronger at V1 compared to V2 and we observed no evidence of effect modification by pregnancy complications, fetal sex, or maternal childhood trauma history. In conclusion, we observed modest evidence of association between OH-PAHs, most notably 2-OH-PHEN, and pCRH in this s le. Additional research using serial measures of PAH exposure is warranted, as is investigation of alternative mechanisms that may link PAHs and timing of birth, such as inflammatory, epigenetic, or oxidative stress pathways.
Publisher: Wiley
Date: 12-1997
DOI: 10.1046/J.1365-2826.1997.00665.X
Abstract: Corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) are two potent stimulators for secretion of proopiomelanocortin (POMC)-derived hormones, from corticotrophs. CRH also stimulates POMC synthesis. Atrial natriuretic peptide (ANP) has been reported to inhibit POMC peptide release and is thought to act through cGMP signalling pathways. A multicolumn cell perifusion system was used to investigate the role of cGMP signalling pathways in CRH- and AVP-stimulated POMC peptide release from primary cultures of ovine or rat anterior pituitary cells. The CRH and/or AVP stimulations were applied at 30 min intervals as 5 min pulses, and the various treatments were infused over a period of 50 min, overlapping with 2 of the stimulations. ANP (10 nM) had no effect on beta-endorphin (betaEP) release from ovine cells, stimulated by 0.5 nM CRH and 5 nM AVP together, or 5 nM CRH and 50 nM AVP separately. Rat anterior pituitary cells were stimulated with 0.05 nM CRH/0.5 nM AVP or 0.5 nM CRH/5 nM AVP and treated with 1 nM or 10 nM ANP, respectively. No inhibition of ACTH or betaEP was observed. Similarly, the nitric oxide donors molsidomine (100 microM), SIN-1 (100 microM) and NaNO2 (100 microM) did not inhibit betaEP release stimulated by 0.5 nM CRH/5 nM AVP in ovine cells. The cGMP analogues 8-bromo-cGMP (10 microM and 100 microM) and dibutyryl cGMP (100 microM) also had no effect on betaEP and ACTH release from ovine or rat anterior pituitary cells. Dexamethasone (8 microM), a synthetic glucocorticoid known to block POMC synthesis and secretion of betaEP and ACTH by a distinct mechanism, was used as a control and suppressed CRH/AVP-stimulated betaEP secretion from ovine anterior pituitary cells. These results contrast with some previous studies and demonstrate that the cGMP signalling pathway in sheep or rat anterior pituitary cells does not directly inhibit secretion of POMC-derived hormones from corticotrophs.
Publisher: MDPI AG
Date: 17-01-2022
DOI: 10.3390/NU14020381
Abstract: Globally, there has been a renewed focus on addressing gestational weight gain (GWG). In Australia, the Department of Health pregnancy care guidelines recommend women be offered routine weighing and receive brief nutritional and physical activity support during antenatal care visits. Women gaining weight outside the Institute of Medicine (IOM)’s weight gain reference values are further recommended to be referred to a dietitian. However, professional and organizational barriers, including an absence of weight gain referral pathways and limited workforce resources, exist with the translation and scaling of these recommendations into practice. This study aimed to explore patterns of GWG among a cohort of Australian pregnant women and to determine if pregnancy weight gains of above or below 2 kg or 5 kg in the second and third trimester can be used to predict total GWG outside recommendations. Sensitivity, specificity, negative, and positive likelihood ratios were calculated. The most predictive time point was 24 weeks’ gestation using the minimum weight change parameter of +/−2 kg, demonstrating reasonable sensitivity (0.81, 95% CI 0.61–0.83) and specificity (0.72, 95% CI 0.61–0.83), resulting in 55% (n = 72/131) of the cohort qualifying for dietetic referral. Given the current health service constraints, a review of dietetic services within maternity care is warranted.
Publisher: Cambridge University Press
Date: 28-07-2005
Publisher: Springer Science and Business Media LLC
Date: 08-2000
DOI: 10.1038/35020651
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.TEM.2012.05.002
Abstract: The timing of human birth has a crucial impact upon the survival of the fetus. New knowledge on the regulation of human birth includes the role of endogenous retroviruses in the formation of the syncytiotrophoblast cells and consequently the secretion of corticotrophin releasing hormone, a hormone linked to gestational length determination. miRNAs have been identified that mediate progesterone withdrawal at labor by suppressing progesterone-induced transcription factors. Progress has also been made in understanding how the contractile machinery of the uterine myocytes is activated at labor and the role of small heat-shock proteins in this process. From this work, new therapeutic targets have been identified that may be used to regulate the onset of labor and improve neonatal mortality.
Publisher: Informa UK Limited
Date: 2001
DOI: 10.3109/10253890109014747
Abstract: The human placenta produces corticotrophin-releasing hormone (CRH) in exponentially increasing amounts during pregnancy with peak levels during labour. CRH in human pregnancy appears to be involved in many aspects of pregnancy including placental bloodflow, placental prostaglandin production, myornetrial function, fetal pituitary and adrenal function and the maternal stress axis. Since fetal cortisol levels are associated with pulmonary development and maturity, placental CRH may have an indirect role in fetal development.Although the precise role of placental CRH in the regulation of gestational length and timing of parturition is unclear it appears to be involved in a placental clock. While glucocorticoids inhibit hypothalamic CRH production they stimulate CRH gene expression in the placenta.This difference may allow the fetal and maternal stress axes to influence this placental clock.Maternal CRH levels are elevated in many pathological conditions of pregnancy where fetal well-being is compromised, and in these situations it may act to maintain a stable intrauterine environment. Therefore, CRH appears to link placental function, maternal well-being, fetal well-being and fetal development to the duration of gestation and the timing of parturition.
Publisher: CRC Press
Date: 08-02-2007
DOI: 10.1201/B13792-9
Publisher: MDPI AG
Date: 29-06-2021
DOI: 10.3390/JCM10132912
Abstract: Preterm birth (PTB) remains the leading cause of infant morbidity and mortality. Despite 50 years of research, therapeutic options are limited and many lack clear efficacy. Tocolytic agents are drugs that briefly delay PTB, typically to allow antenatal corticosteroid administration for accelerating fetal lung maturity or to transfer patients to high-level care facilities. Globally, there is an unmet need for better tocolytic agents, particularly in low- and middle-income countries. Although most tocolytics, such as betamimetics and indomethacin, suppress downstream mediators of the parturition pathway, newer therapeutics are being designed to selectively target inflammatory checkpoints with the goal of providing broader and more effective tocolysis. However, the relatively small market for new PTB therapeutics and formidable regulatory hurdles have led to minimal pharmaceutical interest and a stagnant drug pipeline. In this review, we present the current landscape of PTB therapeutics, assessing the history of drug development, mechanisms of action, adverse effects, and the updated literature on drug efficacy. We also review the regulatory hurdles and other obstacles impairing novel tocolytic development. Ultimately, we present possible steps to expedite drug development and meet the growing need for effective preterm birth therapeutics.
Publisher: The Endocrine Society
Date: 08-1998
DOI: 10.1210/JC.83.8.2916
Publisher: MDPI AG
Date: 09-09-2021
Abstract: The identification and measurement of psychosocial factors that are specific to pregnancy and relevant to gestational weight gain is a challenging task. Given the general lack of availability of pregnancy-specific psychosocial assessment instruments, the aim of this study was to develop a short-form psychosocial assessment tool for the detection of women at risk of excessive gestational weight gain with research and clinical practice applications. A staged scale reduction analysis of the weight-related behaviours questionnaire was conducted amongst a s le of 159 Australian pregnant women participating in the Women and Their Children’s Health (WATCH) pregnancy cohort study. Exploratory factor analysis, univariate logistic regression, and item response theory techniques were used to derive the minimum and most predictive questions for inclusion in the short-form assessment tool. Of the total 49 questionnaire items, 11 items, all 4 body image items, n = 4 attitudes towards weight gain, and n = 3 self-efficacy items, were retained as the strongest predictors of excessive gestational weight gain. These within-scale items were highly correlated, exhibiting high item information function value statistics, and were observed to have high probability (p 0.05) for excessive gestational weight gain, in the univariate analysis. The short-form questionnaire may assist with the development of tailored health promotion interventions to support women psychologically and physiologically to optimise their pregnancy weight gain. Confirmatory factor analysis is now required.
Publisher: Public Library of Science (PLoS)
Date: 30-08-2018
Publisher: Elsevier BV
Date: 12-2006
Publisher: Springer Science and Business Media LLC
Date: 02-03-2018
Publisher: Springer Science and Business Media LLC
Date: 15-04-2013
Abstract: Placental production of corticotrophin releasing hormone (CRH) rises exponentially as pregnancy progresses, and has been linked with the onset of normal and preterm labour. CRH is produced in syncytiotrophoblast cells and production is increased by glucocorticoids and cAMP. It remains unclear whether cAMP acts by inducing differentiation of cytotrophoblasts and/or through induction of syncytialisation. As CRH can stimulate cAMP pathways we have tested whether a feed-forward system may exist in placental cells during syncytialisation. The choriocarcinoma BeWo cell line was treated with cAMP, CRH or vehicle. Cell viability was determined by MTT assay, while apoptosis was analysed by DAPI staining and by FACS. Differentiation was measured by assaying message for hCG and ERVW-1 (syncytin1) by qRT-PCR, as well as the respective protein by ELISA. Fusion of BeWo cells was assessed by co-staining cell membrane and nuclei with CellMask and Hoechst 33342. CRHR1 and CRHR2 mRNA levels were measured by qRT-PCR. We show that cAMP has an inductive effect on syncytialisation, as evidenced by induction of hCG secretion, by ERVW-1 mRNA expression and by formation of multinuclear cells. CRH mRNA expression was found to increase prior to the changes in the other syncytialisation markers. cAMP had an inhibitory effect on BeWo cell viability, but exogenous CRH did not. However, CRH did mimic the differentiation inducing effect of cAMP, suggesting a link between CRH and cAMP signalling in syncytialisation. We also found that treatment of BeWo cells with exogenous CRH resulted in elevated cellular CRHR1 levels. This study suggests a positive feed-forward role exists for CRH in trophoblast cell differentiation, which may underlie the exponential rise in CRH observed as gestation advances.
Publisher: Springer Science and Business Media LLC
Date: 30-08-2023
DOI: 10.1007/S43032-023-01333-6
Abstract: Metabolic inactivation of progesterone within uterine myocytes by 20α-hydroxysteroid dehydrogenase (20α-HSD) has been postulated as a mechanism contributing to functional progesterone withdrawal at term. In humans, 20α-HSD is encoded by the gene AKR1C1 . Myometrial AKR1C1 mRNA abundance has been reported to increase significantly during labor at term. In spontaneous preterm labor, however, we previously found no increase in AKR1C1 mRNA level in the myometrium except for preterm labor associated with clinical chorioamnionitis. This suggests that increased 20α-HSD activity is a mechanism through which inflammation drives progesterone withdrawal in preterm labor. In this study, we have determined the effects of various treatments of therapeutic relevance on AKR1C1 expression in pregnant human myometrium in an ex vivo culture system. AKR1C1 expression increased spontaneously during 48 h culture ( p 0.0001), consistent with the myometrium transitioning to a labor-like phenotype ex vivo , as reported previously. Serum supplementation, prostaglandin F 2α , phorbol myristate acetate, and mechanical stretch had no effect on the culture-induced increase, whereas progesterone ( p = 0.0058) and cAMP ( p = 0.0202) further upregulated AKR1C1 expression. In contrast, culture-induced upregulation of AKR1C1 expression was dose-dependently repressed by three histone rotein deacetylase inhibitors: trichostatin A at 5 ( p = 0.0172) and 25 µM ( p = 0.0115) suberoylanilide hydroxamic acid at 0.5 ( p = 0.0070), 1 ( p = 0.0045), 2.5 ( p = 0.0181), 5 ( p = 0.0066) and 25 µM ( p = 0.0014) and suberoyl bis-hydroxamic acid at 5 ( p = 0.0480) and 25 µM ( p = 0.0238). We propose the inhibition of histone rotein deacetylation helps to maintain the anti-inflammatory, pro-quiescence signaling of progesterone in pregnant human myometrium by blocking its metabolic inactivation. Histone deacetylase inhibitors may represent a class of agents that preserve or restore the progesterone sensitivity of the pregnant uterus.
Publisher: Wiley
Date: 2001
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.AJOG.2021.07.002
Abstract: The onset of the term human parturition involves myometrial gene expression changes to transform the uterus from a quiescent to a contractile phenotype. It is uncertain whether the same changes occur in the uterus during preterm labor. This study aimed to compare the myometrial gene expression between term and preterm labor and to determine whether the presence of acute clinical chorioamnionitis or twin gestation affects these signatures. Myometrial specimens were collected during cesarean delivery from the following 7 different groups of patients: term not in labor (n=31), term labor (n=13), preterm not in labor (n=21), preterm labor with acute clinical chorioamnionitis (n=6), preterm labor with no acute clinical chorioamnionitis (n=9), twin preterm not in labor (n=8), and twin preterm labor with no acute clinical chorioamnionitis (n=5). RNA was extracted, reverse transcribed and quantitative polymerase chain reactions were performed on 44 candidate genes (with evidence for differential expression in human term labor) using the Fluidigm platform. Computational analysis was performed using 2-class unpaired Wilcoxon tests and principal component analysis. Computational analysis revealed that gene expression in the preterm myometrium, irrespective of whether in labor or not in labor, clustered tightly and is clearly different from the term labor and term not-in-labor groups. This was true for both singleton and twin pregnancies. Principal component analysis showed that 57% of the variation was explained by 3 principal components. These 44 genes interact in themes of prostaglandin activity and inflammatory signaling known to be important during term labor, but are not a full representation of the myometrium transcriptional activity. The myometrial contractions associated with preterm labor are associated with a pattern of gene expression that is distinct from term labor. Therefore, preterm labor may be initiated by a different myometrial process or processes outside the myometrium.
Publisher: Portland Press Ltd.
Date: 09-1989
DOI: 10.1042/CS0770323
Abstract: 1. Endogenous opioids have been implicated in the control of breathing in neonates, but their role in ventilatory control in adults remains unclear. 2. We studied the relationship between circulating immunoreactive β-endorphin and the ventilatory and mouth occlusion pressure responses to hypercapnia in 12 healthy male subjects. In addition, we examined the effect of repetitive hypercapnia on plasma β-endorphin and Cortisol levels. 3. A weak but significant negative relationship between the ventilatory response to hypercapnia and basal plasma β-endorphin levels was observed (r = −0.35, P & 0.01). A similar negative relationship was noted between mouth occlusion pressure response to hypercapnia and basal plasma β-endorphin levels (r = −0.36, P & 0.01). 4. Repetitive hypercapnia prevented the fall in plasma Cortisol that occurred under control conditions (P & 0.02) but had no effect on plasma β-endorphin. 5. We conclude that plasma β-endorphin may play a role in the central chemical control of breathing in man.
Publisher: Oxford University Press (OUP)
Date: 30-05-2012
DOI: 10.1111/J.1753-4887.2012.00481.X
Abstract: Research reporting diet during pregnancy in nationally representative s les is limited. This review summarizes the dietary intakes of pregnant women in developed countries and compares them with national recommendations. A systematic search without date limits was conducted. All studies reporting the macronutrient intakes of pregnant women were considered, irrespective of design. Two authors independently identified the studies to be included and assessed the methodological quality. Nutritional adequacy was summarized, with confounding factors considered. Meta-analysis data are reported for developed countries collectively, by geographical region, and by dietary methodology. Energy and macronutrient intakes of pregnant women do not match national recommendations. Energy and fiber intakes were consistently below recommendations, while total fat and saturated fat intakes were generally above recommendations and carbohydrate and polyunsaturated fat intakes were below to borderline low compared with recommendations. A mismatch between dietary practices and macronutrient recommendations in pregnant women is widespread and not well quantified. The implications of these practices are unknown until further research compares maternal diet with short-term and long-term maternal and offspring health outcomes.
Publisher: Elsevier BV
Date: 15-12-2004
DOI: 10.1016/J.PHYSBEH.2004.08.030
Abstract: Dual exposure to endotoxin on postnatal days (PNDs) 3 and 5 is increasingly being used to model the impact of bacterial challenge, in early life, on long-term health outcomes. Currently, however, little is known about how exposure to endotoxin using this model disrupts systems known to program physiological alterations in later life. The aim of the current study was to define, in Fischer 344 rat pups, a framework of the immediate endocrine, metabolic, and behavioural consequences following challenge with 0.05 mg/kg of endotoxin (Salmonella enteritidis) on PNDs 3 and 5. Circulating corticosterone in endotoxin challenged neonates was significantly elevated at all time points assessed on PND 3 (P<0.05), however, by PND 5 this response was attenuated showing a significant elevation only at 4-h post-injection. In these same pups, glucose levels were significantly reduced by 8-h post-injection on PND 3 and remained significantly lower until 8-h post-injection on PND 5 (P<0.05). Finally, the dams of endotoxin challenged pups, exhibited significantly less arched back nursing (P<0.05) but increased levels of off-nest time across the challenge period (P<0.05). These findings demonstrate that postnatal endotoxin exposure impacts on both endocrine and metabolic activity and that alterations in these two systems may in part be mediated by the impact of endotoxin exposure on maternal behaviour.
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1016/J.MVR.2011.07.011
Abstract: Currently, there are no published data on retinal microvasculature size in human infants born at term. The purpose of this study was to determine the normal retinal microvasculature measurements in human infants born at term with normal birth weight and to compare these results with measurements in children and adults. Retinal arteriole and venule measurements were obtained in a cohort of 20 full-term infants. Digital retinal images were obtained from both eyes after pupillary dilation using a digital retinal camera. Measurements of vessel diameter were then obtained using semi-automated software. Twenty infants (9 female infants and 11 male infants) were analyzed. The retinal arteriole diameter was 66.8-123.0 μm (mean, 85.5 (14.3) μm), and the venule diameter was 102.0-167.8 μm (mean, 130.0 (16.0) μm). There were no differences in the arterial or venule diameters between the male and female infants (83.2 (12.2) vs. 88.3 (16.9) P=0.4372 124.3 (16.0) vs. 137.0 (18.0) P=0.08). The arteriovenous ratio was found to be 0.66 (95% CI 0.62-0.71). The coefficient of correlation between the retinal arterioles and venules was 0.56. The retinal arteriole and venule diameters increase as a person matures. The arteriovenous ratio also increases with age. In newborn infants, retinal venules are significantly larger than retinal arterioles. The arteriovenous ratio is smaller in neonates compared to adults indicating the retinal arteriole diameter increases at a different pace compared to retinal venule. Sex does not influence the retinal microvasculature size in infants. The presence of spontaneous retinal hemorrhage and the inability to account for refractive errors were the main limitations of this study.
Publisher: Cambridge University Press (CUP)
Date: 17-01-2019
DOI: 10.1017/S204017441800079X
Abstract: Adverse pregnancy outcomes including prematurity and low birth weight (LBW) have been associated with life-long chronic disease risk for the infant. Stress during pregnancy increases the risk of adverse pregnancy outcomes. Many studies have reported the incidence of adverse pregnancy outcomes in Indigenous populations and a smaller number of studies have measured rates of stress and depression in these populations. This study sought to examine the potential association between stress during pregnancy and the rate of adverse pregnancy outcomes in Australian Indigenous women residing in rural and remote communities in New South Wales. This study found a higher rate of post-traumatic stress disorder, depression and anxiety symptoms during pregnancy than the general population. There was also a higher incidence of prematurity and LBW deliveries. Unfortunately, missing post-traumatic stress disorder and depressive symptomatology data impeded the examination of associations of interest. This was largely due to the highly sensitive nature of the issues under investigation, and the need to ensure adequate levels of trust between Indigenous women and research staff before disclosure and recording of sensitive research data. We were unable to demonstrate a significant association between the level of stress and the incidence of adverse pregnancy outcomes at this stage. We recommend this longitudinal study continue until complete data sets are available. Future research in this area should ensure prioritization of building trust in participants and overestimating s le size to ensure no undue pressure is placed upon an already stressed participant.
Publisher: Springer Science and Business Media LLC
Date: 11-12-2019
Publisher: Elsevier BV
Date: 12-1983
DOI: 10.1016/0006-8993(83)90093-8
Abstract: Cerebrospinal fluid (CSF) s les were taken from rats implanted with chronic cisternal cannulae and assayed for methionine-enkephalin, beta-endorphin and corticotropin (ACTH). Immobilization stress had little apparent effect on immunoreactive levels of the peptides in the CSF. Gel chromatographic analysis of the beta-endorphin- and ACTH-immunoreactive profiles in rat CSF revealed several peaks. beta-Endorphin-immunoreactive peaks were present at the expected positions of pro-opiocortin, beta-lipotropin and beta-endorphin. ACTH-immunoreactive peaks eluted at positions corresponding to pro-opiocortin, the 20-23K ACTH biosynthetic intermediate, 14K ACTH, and 4.5K ACTH. These results suggest that rat CSF contains peptides of the pro-opiocortin family similar to those previously described in rat pituitary.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.MIDW.2018.12.002
Abstract: Postnatal care is critical to detect and manage postpartum complications in the early stages as well as to prevent potentially life-threatening health conditions that lead to maternal death. However, postnatal care utilization is persistently low in Ethiopia. The aim of this study is to assess the magnitude and correlates of postnatal care utilization among reproductive aged women in Kersa district, in eastern Ethiopia. A community based cross-sectional study was conducted in ten randomly selected sub-districts in Kersa district. Respondents were recruited using systematic random s ling techniques. Data were collected by an interviewer-administered questionnaire using iPads. A total of 1206 respondents' data were considered in the analysis. Frequency and percentage distributions of the variables were performed. Bivariate and multivariate logistic regression analyses were undertaken to identify the predisposing, enabling and need factors associated with postnatal care utilization. An Odds Ratio with 95% confidence interval was used to ascertain the direction and strength of the association. Less than one in thirteen women attended postnatal care after their last delivery in the study community. The multivariate analysis demonstrated that postnatal care utilization is associated with receiving education on maternal health, best friend's use of maternal care, head of the household, and experience of postpartum complications. Receiving education on maternal health (AOR, 2.32 95% CI: 1.38, 3.89) and best friend's use of maternal care (AOR, 2.41 95% CI: 1.39, 4.19) were significant predisposing factors that independently predicted postnatal care utilization. Furthermore, head of the household was a significantly associated enabling factor for postnatal care utilization (AOR, 0.24 95% CI: 0.07, 0.81). The experience of postpartum complications (AOR, 0.10 95% CI: 0.05, 0.20) was the only need factor that was associated with postnatal care utilization. Postnatal care utilization is extremely low in the study district. Strengthening health education and promotion activities on maternal health, peer education programs within the women's social networks, strengthening women empowerment programs, and women's mobilization to seek postnatal care before the occurrence of complications are essential actions that can improve postnatal care utilization.
Publisher: Springer Science and Business Media LLC
Date: 04-2004
DOI: 10.1007/S00018-004-4030-2
Abstract: Corticotrophin-releasing hormone (CRH) plays a major role in mechanisms controlling human pregnancy and parturition. Gene regulation by progesterone may be a key point in the control of placental CRH production. Studies in primary placental cells show that antagonism of progesterone activity or production by RU486 or trilostane leads to an increase in CRH promoter activity. This effect can be reversed by the addition of progesterone. Overexpression of progesterone receptor A (PR-A) or glucocorticoid receptor resulted in a decrease in CRH promoter activity following progesterone treatment, whereas an increase in promoter activity was observed with overexpressed PR-B. Studies including mutation of the cAMP regulatory element (CRE) confirm this site to be essential for the progesterone-mediated effects. In summary, our results demonstrate that progesterone regulates CRH gene transcription via a CRE in the CRH promoter and that PR-A and PR-B exhibit different actions in the regulation of CRH gene expression.
Publisher: Elsevier BV
Date: 08-2011
DOI: 10.1016/J.PLACENTA.2011.05.005
Abstract: Chronic maternal asthma is associated with reduced growth of the female fetus and normal growth of the male fetus. The mechanisms that control the differential effects of maternal asthma on the fetus have not been fully elucidated but alterations in placental function may play a role. In the current study we have used microarray platform to examine fetal sex-specific global changes in placental gene expression in pregnancies complicated by asthma as compared to non-asthmatic subjects. Placental RNA was extracted from 11 control subjects and 38 asthmatic subjects. Labeled cDNA was hybridized to an oligonucleotide chip with 1700 double spotted well-characterized human genes. Global gene expression data analysis and visualization were performed using the Binary Tree-Structured Vector Quantization (BTSVQ) software. Functional relationships of differentially expressed genes were assessed using protein-protein interaction database I2D, network analysis and visualization software NAViGaTOR and Ingenuity Pathway Analysis software. Overall, 65 genes were found to be altered in placentae of pregnancies complicated by asthma. Of these, only 6 genes were altered in male placentae. There were 59 gene changes in female placentae of asthmatic mothers relative to control placentae. Some of the sex-specific genes were associated with growth, inflammation and immune pathways. There are sex-specific alterations in placental gene expression in the presence of maternal asthma. Given that many of the identified genes in the female placentae were associated with or involved in cellular growth and tissue development, these may contribute to the sexually dimorphic difference in fetal growth in response to maternal asthma.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 23-12-2015
DOI: 10.1126/SCITRANSLMED.AAD9788
Abstract: Blocking the transient receptor potential vanilloid 4 (TRPV4) channel may be a viable new therapeutic approach to preterm labor (Ying et al ., this issue).
Publisher: Elsevier BV
Date: 04-1985
DOI: 10.1016/0304-3940(85)90450-1
Abstract: In 5 normal adult men, histamine was infused i.v. for 5 min at 20 micrograms/kg/h and at 80 micrograms/kg/h on two occasions one week apart. Diastolic blood pressure fell and heart rate, plasma adrenaline and noradrenaline all rose in a dose-dependent manner, but plasma methionine-enkephalin (Met-Enk) concentrations were unchanged. These results indicate that while Met-Enk may be co-stored with catecholamines (CAs) in the adrenal medulla in at least this paradigm, circulating concentrations of CAs may be altered without similar changes in plasma Met-Enk immunoreactivity.
Publisher: The Endocrine Society
Date: 11-2003
Abstract: CRH plays a central role as a mediator of the hypothalamic-pituitary-adrenal axis and stress response and is a potent vasodilator. Previously, we have shown that CRH causes a gender-specific vasodilation in human skin, although the mechanism by which CRH operates is unclear. CRH causes mast cell degranulation in rat skin. As such, histamine and other mast cell-derived factors may be indirectly responsible for the vasodilatory effects of CRH, although CRH is also known to act directly on the vasculature. CRH-induced vasodilation in human skin was examined using laser Doppler flowmetry and iontophoresis in adult females. CRH (1 nM) was administered iontophoretically to the forearm, and blood flow was measured simultaneously in the same area by laser Doppler. CRH-induced dilation of the skin microvasculature was significantly reduced in the presence of the mast cell degranulation inhibitor, sodium cromoglycate, the histamine H(1)-antagonist, promethazine, or the H(2)-antagonist, ranitidine. CRH-induced dilation was also significantly reduced in the presence of the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester, or the cyclooxygenase inhibitor, piroxicam. These findings provide novel evidence that CRH-induced vasodilation in human skin occurs via mast cell degranulation and is principally mediated by histamine and, to a lesser extent, by prostacyclin and nitric oxide.
Publisher: S. Karger AG
Date: 2002
DOI: 10.1159/000063683
Abstract: This study describes the effect of antalarmin on basal and stimulated activity of the hypothalamo-pituitary-adrenal (HPA) axis function in the late gestation ovine fetus. Fetuses received antalarmin (15 mg/h i.v.) or vehicle (cremophor El 50% in ethanol) from day 130 gestational age. Antalarmin infusion did not significantly affect immunoreactive corticotropin (ir-ACTH) concentrations, although there was a tendency for ir-ACTH to be lower and cortisol concentrations were lower in the antalarmin-treated fetuses (p 0.01). The ir-ACTH response to corticotropin-releasing hormone (CRH) challenge was attenuated (p 0.05) in the antalarmin-treated fetuses, but neither antalarmin- nor vehicle-treated fetuses had significant cortisol responses to CRH. The ir-ACTH response to hypoxia was diminished (p 0.05) in the antalarmin-treated fetuses while the cortisol responses of antalarmin- and vehicle-treated fetuses were indistinguishable. Deconvolution analysis revealed no effect of antalarmin treatment on ir-ACTH secretory dynamics. In contrast, antalarmin decreased (p 0.05) basal, mean and integrated cortisol. The plasma cortisol responses of antalarmin- and vehicle-treated fetuses to exogenous ACTH sub –24 /sub were indistinguishable. These data indicate that, while antalarmin inhibits CRH- and stress-induced ir-ACTH secretion, basal ir-ACTH secretion may be less affected by antalarmin treatment. Paradoxically, cortisol secretion is impaired by antalarmin infusion, although adrenal responsiveness to ACTH is not impaired. These results confirm a role for CRH in stress-induced ACTH secretion in the ovine fetus, though its role in the regulation of basal ACTH and cortisol secretion is unclear.
Publisher: Elsevier BV
Date: 10-1985
DOI: 10.1016/0304-3940(85)90594-4
Abstract: Plasma methionine-enkephalin (Met-Enk) immunoreactivity has been determined in 24 patients with varying degrees of renal impairment and 14 patients with hepatic failure. Plasma Met-Enk immunoreactivity correlated inversely with creatinine clearance (r = -0.71, P less than 0.001) but was not affected by even severe hepatic failure in the absence of renal impairment. In two patients, with renal failure and elevated plasma prolactin, administration of naloxone (16 mg) had no effect on circulating prolactin concentrations. These studies indicate that the kidney has a major role in Met-Enk metabolism while the liver does not, and further suggest that elevated circulating endogenous opiates are not responsible for the increased production of prolactin found in renal failure.
Publisher: Springer Science and Business Media LLC
Date: 04-2009
Abstract: To explore how progesterone affects human pregnancy, we identified the progesterone target cells within the fetal membranes (amnion, chorion, and decidua) at term by assessing the extent of expression and localization of the nuclear progesterone receptors, progesterone receptor-A and progesterone receptor-B. Fetal membranes (separated into amnion and chorion-decidua) were obtained after term cesarean deliveries performed before (n = 7) and after (n = 7) labor onset. Nuclear progesterone receptor expression was determined by the abundance of nuclear progesterone receptor mRNAs (by quantitative reverse transcriptase-polymerase chain reaction) and proteins (by western blotting). Localization of nPRs was determined by immunohistochemistry. Progesterone receptor-A and progesterone receptor-B mRNA and protein levels were highest in the chorion-decidua and did not change in association with labor. Nuclear progesterone receptor mRNAs and proteins were barely detectable in amnion. Nuclear progesterone receptor immunostaining was detected only in the nucleus of decidual cells. These findings suggest that the decidua, and not the amnion and chorion, is a direct target for nuclear progesterone receptor-mediated progesterone actions during human pregnancy.
Publisher: Elsevier BV
Date: 02-2002
Abstract: The purpose of this study was to examine the relationship of maternal serum activin A, inhibin A, and follistatin with fetal growth and placental function. Inhibin A, activin A, and follistatin were measured in maternal serum that was stored from normally grown (control subjects, n = 50) and small-for-gestational-age pregnancies (n = 49), prospectively classified as normal small-for-gestational-age pregnancy or fetal growth-restricted pregnancy with the use of umbilical artery Doppler ultrasound. Activin A and inhibin A were significantly increased in fetal growth-restricted pregnancies compared with control subjects (activin A: regression coefficient, 0.54, P <.001 inhibin A: regression coefficient, 0.47, P =.003). The activin:follistatin ratio was significantly higher in fetal growth-restricted pregnancies compared with control subjects (P <.001). There were no significant differences between analyte levels of normal small-for-gestational-age pregnancies and control subjects. Maternal serum activin A, inhibin A, and activin:follistatin ratio are raised in fetal growth-restricted pregnancies but not in normal small-for-gestational age pregnancies. This provides further evidence of the difference between subgroups within small-for-gestational-age pregnancies and emphasizes the need to stratify for this in research.
Publisher: The Endocrine Society
Date: 02-2013
DOI: 10.1210/EN.2012-2262
Publisher: The Endocrine Society
Date: 08-2002
Abstract: CRH and estrogens, produced by placental trophoblasts, have been suggested to play pivotal roles in the control of human parturition. Estrogen has been shown to affect hypothalamic CRH expression. Therefore, we evaluated 17 beta-estradiol (E2) in the regulation of CRH gene expression in placental cells. E2 inhibited CRH mRNA expression in a dose-dependent manner, which paralleled the decrease in CRH protein levels in culture media. A complete estrogen receptor (ER) antagonist, ICI 182780, not only blocked repression of CRH mRNA levels by E2, but up-regulated CRH mRNA and protein synthesis. An ER alpha-mixed agonist/antagonist and ER beta antagonist, 4-hydroxytamoxifen, also down-regulated CRH gene expression. Using quantitative RT-PCR, we found that placental trophoblasts express predominantly the ER alpha form of the receptor. Transient transfection assays conducted in the choriocarcinoma cell line JEG-3 demonstrated that E2 repressed CRH promoter activity, whereas the antagonist ICI 182780 up-regulated CRH promoter activity when ER alpha was cotransfected. These studies demonstrate that E2 represses placental CRH gene expression through an ER alpha-mediated mechanism. Estrogen may therefore modulate placental CRH production, influencing the rate of rise of maternal plasma CRH concentrations and potentially the length of gestation.
Publisher: The Endocrine Society
Date: 05-2000
DOI: 10.1210/JC.85.5.1937
Publisher: Informa UK Limited
Date: 2002
DOI: 10.1080/078538902317338616
Abstract: Preterm delivery is responsible for the vast majority of neonatal mortality in developed countries and is also associated with substantial long-term morbidity. The incidence of preterm birth remains between 6-10% despite many advances in our understanding of the physiology of human parturition. Biochemical markers have been used in an attempt to identify more accurately those women, amongst high and low-risk groups who will deliver preterm, from their counterparts who will go on to deliver at term. Only by accurately identifying those women early, who will eventually deliver preterm, will specific interventions be able to be used in order to try and treat the cause or delay delivery until a safer time for the fetus. The clinical utility of these markers when used alone in an unselected population remains limited. As our understanding of the pathophysiology of preterm delivery improves, the challenge lies for researchers to combine these markers in the most effective way to unravel the complex biological system of parturition and improve the predictive capability of a biochemical test for prematurity.
Publisher: BMJ
Date: 13-07-2010
Abstract: Fetal growth inhibition is a known sequelae of in utero glucocorticoid exposure and has long-term consequences for adult health. Sex-specific fetal growth patterns are observed in pregnancies with maternal asthma and may be due to differential sensitivity of the placenta to glucocorticoids. It is currently unknown whether expression of the placental glucocorticoid receptor (GR) becomes altered with asthma or the use of inhaled corticosteroids. Pregnant women with mild asthma (n=52), moderate-severe asthma (n=71) and without asthma (n=51) were recruited at John Hunter Hospital, Newcastle, Australia. At delivery, placentae and cord blood were collected, and fetal sex and birth weight were recorded. Placental GR heterogeneous nuclear RNA (hnRNA), mRNA and protein were measured and cord blood cortisol concentrations were assessed. Placental GR gene activity increased with cortisol exposure but decreased with inhaled corticosteroid treatment (p=0.05). With maternal asthma, female birth weight centiles were inversely associated with cortisol (r=-0.286, p=0.017) and, despite a decrease in placental GR mRNA (p=0.003), placental GRalpha protein levels were unchanged. In males, no change to cortisol, birth weight or placental GR were evident in pregnancies with asthma. Together, these results indicate that in pregnancies complicated by asthma, placental GR gene activity, but not mRNA expression or protein levels, is dependent on cortisol and inhaled corticosteroid treatment. The sex-specific associations between cortisol and birth weight observed in pregnancies with asthma are not due to altered GR expression however, they may be due to differential glucocorticoid sensitivity via preferential transcription of GR isoforms or post-translational modifications.
Publisher: Springer Science and Business Media LLC
Date: 12-2018
Publisher: Wiley
Date: 16-03-2020
DOI: 10.1113/EP088155
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.AJOG.2017.11.574
Abstract: Small for gestational age, defined as birthweight <10th percentile for gestational age, is known to be associated with clinically meaningful impairments in health and development. The effects of variation within the normal range of birthweight percentile on perinatal mortality and childhood education remain less well defined. We sought to quantify the association among birthweight percentile, perinatal mortality, and educational outcomes and to determine the optimal birthweight percentile for those outcomes in Aboriginal and non-Aboriginal Australian children. This was a retrospective cohort study. Perinatal data for all children born in the Northern Territory, Australia, from 1999 through 2008 were linked to measures of educational attainment at age 8-9 years. Multivariable analysis was used to determine the optimal birthweight percentile for low perinatal mortality and high reading and numeracy scores. The birth cohort contained 35,239 births (42% Aboriginal), of which 11,214 had linked and valid education records. Median birthweight percentile was 29.2 in Aboriginal infants and 44.0 in non-Aboriginal infants. The odds of perinatal mortality decreased by 4% with each 1-percentile increase birthweight percentile overall (adjusted odds ratio, 0.96 P = .000) and lowest mortality rates were at the 61st and 78th percentile in Aboriginal and non-Aboriginal infants, respectively. Although birthweights <10th percentile were associated with greatly increased odds of perinatal mortality, the increased risk extended well beyond this cut-off. Birthweight percentile was also positively correlated with scores in reading (P = .000) and numeracy (P = .000). In non-Aboriginal children, reading and numeracy scores peaked at the 66th percentile, but for Aboriginal children there was continuous benefit with increasing birthweight percentile. Birthweight percentile explained 1% of the variation in education outcomes, with much greater variation explained by other perinatal and sociodemographic factors. Birthweights between the 50th-93rd percentiles were most consistently associated with both low perinatal mortality and high reading and numeracy scores, suggesting that small for gestational age does not sufficiently capture the risks associated with variation in fetal growth. Our data indicate that the effect of birthweight percentile accounts for 1% of variation in perinatal and education outcomes.
Publisher: American Chemical Society (ACS)
Date: 08-06-1999
DOI: 10.1021/JM9900117
Publisher: Wiley
Date: 10-1999
DOI: 10.1111/J.1471-0528.1999.TB08111.X
Abstract: To test whether maternal corticotrophin-releasing hormone levels are elevated in the mid- trimester for those women who subsequently had spontaneous preterm delivery and to assess the clinical utility of the measurement in the prediction of preterm delivery. A prospective observational study. Department of Obstetrics and Gynaecology, Prince of Wales Hospital, Hong Kong. 1047 low risk pregnant women recruited at 15-20 weeks of gestation. Venous s les were assayed for levels of corticotrophin-releasing hormone. The investigators responsible for the laboratory assay were blinded to the obstetric outcome. Incidence of preterm, term and post-term pregnancies. Those who were delivered spontaneously at a preterm gestational age (before 34 weeks) had significantly higher corticotrophin-releasing hormone levels in the mid-trimester, compared with those who were delivered at term or post-term. There was a trend towards lower corticotrophin-releasing hormone levels with more advanced gestational age at delivery. When the measurement of corticotrophin- releasing hormone was used to predict delivery before 34 weeks, the best cut off was 1.9 MoM, which produced a sensitivity of 72.7% and specificity of 78.4%. This translated to a positive predictive value of 3.6%, negative predictive value of 99.6% and relative risk of 9.4 when the background prevalence of spontaneous preterm delivery before 34 weeks was 1.1%. The likelihood ratio was 3.4. Mid-trimester maternal corticotrophin-releasing hormone levels are elevated in pregnancies destined to deliver preterm before 34 weeks. When used alone in a low risk population, the measurement has a low predictive power for preterm delivery. However, the likelihood ratio of 3 4 implies that in high risk populations the test may be considerably more valuable.
Publisher: Wiley
Date: 09-1981
DOI: 10.1111/J.1365-2265.1981.TB00668.X
Abstract: Highly regioselective acylation has been observed in 7,8-dihydroxy-4-methylcoumarin (DHMC) by the lipase from
Publisher: Wiley
Date: 09-2019
DOI: 10.14814/PHY2.14227
Publisher: Springer Science and Business Media LLC
Date: 04-2007
Abstract: Immunoblotting is used to characterize the various nuclear progesterone receptor (nPR) isoforms present in tissues however, the success of this technique is dependent on the specificity of the primary nPR antibody. The authors investigate the specificity of a frequently used nPR antibody, sc-538, in total protein from human myometrium and a myometrial cell line (PHM1-31). Using immunoblotting, 2 sc-538 immunoreactive bands at 100 and 55 kDa were detected. The bands were extracted and identified by 1-dimensional liquid chromatography mass spectrometry. The predominant protein in the 100-kDa band was alpha-actinin. The dominant proteins in the smaller band were vimentin (57 kDa) and desmin (53 kDa). Myometrial lysate was immunoprecipitated with sc-538, and immunoblotting of the immunoprecipitate with antibodies to alpha-actinin, desmin, and vimentin confirmed the presence of these proteins. The sc-538 nPR antibody therefore cross-reacts with cytoskeletal proteins that could be misinterpreted as nPR isoforms. Such misinterpretation has confused the progesterone response literature.
Publisher: Informa UK Limited
Date: 2002
DOI: 10.1076/APAB.110.1.94.897
Abstract: The first target autoantigen to have been identified in lymphocytic hypophysitis is a 49 kDa protein, identified as alpha-enolase. Pituitary autoimmunity is strongly associated with pregnancy and we have shown that pituitary autoantibodies from patients with peripartum lymphocytic hypophysitis also recognise enolase in the placenta. Enolase exists in different forms as a number of isoenzymes, which are homo- or heterodimers of three subunits, alpha, beta and gamma. alphaalpha-enolase is ubiquitous, betabeta-enolase is muscle-specific and gammagamma-enolase, which is restricted to neuronal tissue and neuroendocrine cells, is known as neuron-specific enolase (NSE). NSE is expressed in normal human pituitary and pituitary neoplasms. The current study investigated which isoforms of enolase in pituitary and placenta reacted with the sera of patients with lymphocytic hypophysitis. Immunoblotting of two-dimensional gels of human pituitary cytosolic proteins showed that autoantibodies in patient sera react with both an acidic form, and more neutral forms of enolase. Immunoblotting with a monoclonal antibody to NSE confirmed the identity of the acidic enolase isoform as the gammagamma-isoform in both pituitary and placental s les. Gamma-enolase, i.e. NSE, was detected by immunohistochemistry in term placenta in decidua, syncytiotrophoblasts, anchoring villi and terminal villi. Our study is the first to describe the cellular localisation of NSE in normal human placenta, thus establishing a direct link between pituitary and placental autoantigens. This link provides a theoretical basis for the strong prediliction of lymphocytic hypophysitis to occur during or after pregnancy.
Publisher: Cambridge University Press (CUP)
Date: 08-11-2013
DOI: 10.1017/S2040174413000494
Abstract: Rates of chronic kidney disease (CKD) among Indigenous groups in Australia exceed non-Indigenous rates eight-fold. Using kidney volume as a surrogate for nephron number, we carried out a study to determine if Indigenous neonates have a smaller kidney volume (and thus a reduced nephron number) from birth compared with non-Indigenous neonates. We recruited term and preterm neonates ( weeks) at a tertiary care neonatal unit over a 12 months period. Preterm neonates were assessed (renal sonography and renal function measurement) at 32 weeks corrected age (CA) and again at 38 weeks CA when blood pressure was also measured. All term neonates were assessed in the first post-natal week, including renal sonography, renal function and blood pressure measurement. The primary outcome measured was total kidney volume (TKV) and estimated glomerular filtration rate (eGFR) was a secondary outcome. Data was available for 44 preterm (11 Indigenous) and 39 term (13 Indigenous) neonates. TKV of Indigenous neonates was significantly lower at 32 weeks [12.0 (2.0) v. 15.4 (5.1) ml P =0.03] and 38 weeks CA [18.6 (4.0) v. 22.6 (5.9) ml P =0.04] respectively. Term Indigenous neonates also had smaller kidney volumes compared with non-Indigenous neonates. Despite a smaller kidney volume (and reduced nephron number), Indigenous neonates did not have a significantly lower eGFR. Indigenous neonates achieve similar eGFRs to Non-Indigenous neonates, presumably through a higher single nephron filtration rate. This places Indigenous neonates at a greater risk of long-term kidney damage later in life.
Publisher: Public Library of Science (PLoS)
Date: 04-2015
Publisher: BMJ
Date: 10-2020
DOI: 10.1136/BMJOPEN-2020-037532
Abstract: To assess spatial variations in modern contraceptive use and to identify factors associated with it among married women in Ethiopia. Cross-sectional analysis of population-based and health facility data. Ethiopia Demographic and Health Survey data linked to Service Provision Assessment data. 8473 married women and 1020 facilities that reported providing family planning services. A linked secondary data analysis of population and health facility data was carried out. Both multilevel and spatial analyses were conducted to identify key determinants of women’s use of modern contraceptive and spatial clustering of modern contraceptive use. Modern contraceptive use. About 24% of the variation in the use of modern contraception was accounted for by location. A one-unit increase in the mean score of health facilities’ readiness to provide short-term modern contraceptives in a typical region was associated with a 20-fold increase in the odds of modern contraceptive use (adjusted OR (AOR) 20.49, 95% CI 1.44 to 29.54). In the spatial analysis, it was found that Addis Ababa and the Amhara region had high clusters of modern contraceptive use rates. On the other hand, low rates of contraceptive use were clustered in the Afar and Somali regions. There were significant variations in the use of modern contraceptives across the different regions of Ethiopia. Therefore, regions with low contraceptive rates and high fertility rates should be targeted for scaling up and tailoring of services to the culture and lifestyles of the population of those regions.
Publisher: Elsevier BV
Date: 08-2006
DOI: 10.1016/J.AJOG.2006.01.103
Abstract: The object of this study was to determine the effects of maternal tocolysis with glycerol trinitrate (GTN) patches on the neurodevelopment of infants. This was a randomized, multicenter, controlled trial comparing the efficacy of GTN patches with standard beta2 agonist as tocolytic therapy. The previously reported outcomes of this study indicated no difference in neonatal mortality or morbidity to hospital discharge. One hundred fifty-six surviving infants from 2 Australian centers were psychometrically assessed using the Griffiths Mental development Scales (revised) at 18 months of age. There was no difference in psychometric performance between those infants enrolled in either the GTN (81 infants) or beta2 agonist (75 infants) arm of the study. This randomized trial supports no significant difference between GTN patches in comparison with standard beta2 agonist for tocolytic therapy. The results underscore the association between premature labor and adverse infant outcomes.
Publisher: Elsevier BV
Date: 07-1999
DOI: 10.1016/S0002-9378(99)70461-8
Abstract: Many women who have preterm labor have abnormally high plasma concentrations of the placental peptide corticotropin-releasing hormone and the fetal product alpha-fetoprotein in early pregnancy. This study was designed to evaluate the ability of these biochemical tests and a clinical risk factor score to prospectively discriminate pregnancies at high risk for preterm delivery. Eight hundred sixty women were studied prospectively from the early second trimester until delivery. A risk factor score for preterm delivery was calculated from the clinical history and maternal plasma corticotropin-releasing hormone and alpha-fetoprotein concentrations were measured by radioimmunoassay between 17 and 30 weeks' gestation. The risk factor score, corticotropin-releasing hormone concentration, and alpha-fetoprotein concentration for each woman were expressed as in idual odds or likelihood ratios for preterm delivery and as a combined risk estimate derived from the 3 tests. Sixty women had preterm deliveries (n = 37 spontaneous labor, n = 23 planned deliveries), and these women had significantly higher concentrations of corticotropin-releasing hormone (median 1.92 multiples of the median) and alpha-fetoprotein (median 1.32 multiples of the median) than did women with term deliveries (median 1.00 multiples of the median, P /=10 in 28% of women with preterm delivery and 7% of women with term delivery. The combination of all 3 markers resulted in a higher detection rate and a higher positive predictive value than the risk factor score, corticotropin-releasing hormone concentration, or alpha-fetoprotein concentration alone, correctly discriminating 37% of women who would have preterm deliveries with a false-positive rate of 5%. The positive predictive value was also 37% (odds of being affected given a positive result were 1:1.7). The combination of measurement of maternal plasma corticotropin-releasing hormone and alpha-fetoprotein concentrations in the second trimester with risk factor scoring provides a more accurate indicator of the risk of preterm delivery than does risk factor scoring alone. This method of risk assessment may therefore be of use in targeting prevention strategies.
Publisher: Elsevier BV
Date: 11-1991
DOI: 10.1016/0196-9781(91)90230-M
Abstract: A 41 amino acid peptide, probably identical in structure to human corticotropin releasing factor, was isolated from 70 equine hypothalami by methanol extraction, immunoaffinity chromatography and single step of reverse phase HPLC. The amino acid sequence was determined by gas phase sequence analysis. Probable carboxyl terminal amidation was demonstrated by similar retention times for equine and human corticotropin releasing factor on reverse phase HPLC at pH 8. The likely structure of equine corticotropin releasing factor is: Ser-Glu-Glu-Pro-Pro- Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Met-Ala-Arg- Ala-Glu - Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys-Leu-Met-Glu-Ile-Ile-NH2. The purified peptide is equipotent with human corticotropin releasing factor in an in vitro bioassay and in a human plasma binding protein assay.
Publisher: Oxford University Press (OUP)
Date: 11-1995
Abstract: Clifton VL, Owens PC, Robinson PJ, Smith R. Identification and characterization of a corticotrophinreleasing hormone receptor in human placenta. Eur J Endocrinol 1995 :591–7. ISSN 0804–4643 Corticotrophin-releasing hormone (CRH) causes vasodilatation in the human fetal–placental circulation and has paracrine actions in placental tissue, suggesting that CRH receptors may be present in the human placenta. We have now identified and characterized placental CRH binding sites and compared them to those described previously in human myometrium and rat pituitary. Radiolabelled ovine CRH binding to placental membranes was pH-, time-, temperature- and alent cation-dependent and was reversible in the presence of 1 μmol/l unlabelled ovine CRH. Scatchard analysis of placentae delivered vaginally or by elective caesarean section revealed dissociation constants (K d ) of 214.5 ± 84 pmol/l (N = 8) and 45.4 ± 23.9 pmol/l (N = 9), respectively. The K d for caesarean placental binding sites was similar to that of human myometrium (59.6 pmol/l, N = 3) and rat pituitary (82.5 pmol/l, N = 3) receptors. However, in vaginally delivered placentae the CRH binding sites had a much lower affinity (p 0.05). The receptor densities (B max ) of vaginally delivered and caesarean-delivered placentae were 28.6 ± 9.6 and 6.1 ± 2.8 fmol/mg, respectively (p 0.05). Chemical cross-linking studies using disuccinimidyl suberate indicated that the molecular weight of the CRH receptor in the placenta and rat pituitary is 75 kD. We conclude that there is a high-affinity population of CRH binding sites in the human placenta that are physicochemically similar to pituitary and myometrial CRH receptors. The CRH receptor properties in the placenta change in response to labour, when CRH levels in maternal blood are highest, suggesting that placental CRH may regulate its receptor. R Smith, Endocrinology Unit, John Hunter Hospital, Locked Bag 1, Hunter Regional Mail Centre, Newcastle, NSW 2310, Australia
Publisher: Springer Science and Business Media LLC
Date: 17-06-2022
DOI: 10.1007/S43032-022-01000-2
Abstract: The intracellular signaling pathways that regulate myometrial contractions can be targeted by drugs for tocolysis. The agents, 2-APB, glycyl-H-1152, and HC-067047, have been identified as inhibitors of uterine contractility and may have tocolytic potential. However, the contraction-blocking potency of these novel tocolytics was yet to be comprehensively assessed and compared to agents that have seen greater scrutiny, such as the phosphodiesterase inhibitors, aminophylline and rolipram, or the clinically used tocolytics, nifedipine and indomethacin. We determined the IC
Publisher: American Thoracic Society
Date: 12-2003
Publisher: American Thoracic Society
Date: 15-08-2001
DOI: 10.1164/AJRCCM.164.4.2009119
Abstract: Asthma during pregnancy is associated with low-birthweight neonates at term but the mechanisms that cause this outcome are presently unknown. Changes in placental vascular function resulting from asthma or its treatment could contribute to altered fetal growth. We have prospectively followed women with asthma and a control group of women without asthma during their pregnancies, classified them based on asthma severity and glucocorticoid intake, and monitored fetal development and placental blood flow using Doppler ultrasound at 18 and 30 wk gestation. The placentae from these women were collected after delivery and vascular responses to dilator and constrictor agonists assessed using an in vitro placental perfusion method. At 18 wk gestation, umbilical artery flow velocity waveforms were significantly reduced in the moderate and severe asthmatic groups and in those women using high-dose inhaled glucocorticoid for the treatment of their asthma (ANOVA, p 0.05). Corticotropin-releasing hormone (CRH), a potent vasodilator that acts via the nitric oxide pathway, caused a dose-dependent vasodilatory response in all placentae in vitro. However, CRH-induced dilation was significantly reduced in moderate and severe asthmatics (ANOVA, p < 0.05). Vasoconstrictor responses to potassium chloride and prostaglandin F(2alpha) were reduced in placentae from moderate and severe asthmatic women (ANOVA, p < 0.05). These studies demonstrate significant differences in placental vascular function in pregnancies complicated by asthma, which may relate directly to the asthma or be a consequence of the associated glucocorticoid treatment. These changes in vascular function in asthmatic pregnancies may contribute to the low-birthweight outcome observed in this condition.
Publisher: Cambridge University Press (CUP)
Date: 27-06-2016
DOI: 10.1017/S2040174416000325
Abstract: Indigenous Australians continue to experience disparities in chronic diseases, many of which have nutrition-related trajectories. Optimal nutrition throughout the lifespan is protective for a number of adverse health outcomes, however little is known about current dietary intakes and related anthropometric outcomes of Indigenous women and their infants. Research is required to identify nutrition issues to target for health promotion activities. The Gomeroi gaaynggal programme is an ongoing, prospective cohort of pregnant Indigenous Australian women and their children. A cross-sectional examination of postnatal dietary intakes and anthropometric outcomes of mothers and children are reported. To date, 73 mother–child dyads have participated postpartum . Breastfeeding initiation was 85.9% and median (interquartile range) duration of any breastfeeding was 1.4 (0.5–4.0) months. Infants were introduced to solid foods at 5.0 months (4.0–6.0) and cow’s milk at 12.0 (10.0–13.0) months. At 12 months postpartum , 66.7% of women were overweight or obese, 63.7% at 2 years. Compared with recommendations, reported median maternal nutrient intakes from 24-h recall were low in fibre, folate, iodine, calcium, potassium and vitamin D and high in proportions of energy from total and saturated fat. Limitations of this study include a small s le size and incomplete data for the cohort at each time point. Preliminary data from this ongoing cohort of Indigenous Australian women and children suggest that women may need support to optimize nutrient intakes and to attain a healthy body weight for themselves and their children.
Publisher: Elsevier BV
Date: 2011
DOI: 10.1016/J.AJOG.2010.08.014
Abstract: The objective of the study was to evaluate the clinical, sonographic, and hormonal variables that influence the success of labor induction in nulliparous postterm pregnancies. Fifty nulliparous women with a single postterm pregnancy receiving a slow-release prostaglandin estradiol pessary were prospectively enrolled, and clinical characteristics were analyzed in relation to success of induction of labor. Clinical, sonographic, and hormonal variables were analyzed by univariate statistical analysis and multivariate logistic regression for the prediction of successful induction. The group of patients delivering within 24 hours differed significantly from the remaining patients by higher Bishop scores, body mass indices, estradiol serum concentrations, estriol to estradiol ratios, and shorter cervices. The combination of cervical length and estriol to estradiol ratio achieved a sensitivity of 100% (95% confidence interval, 71.3-100%) and a specificity of 94.1% (95% confidence interval, 80.3-99.1%). Cervical length and the estriol to estradiol ratio represent good predictive indicators of the response to the induction of labor in postterm pregnancies.
Publisher: Elsevier BV
Date: 08-1998
DOI: 10.1016/S0165-0378(98)00023-0
Abstract: Although corticotrophin releasing hormone (CRH) was initially identified as a hypothalamic peptide it is also synthesised in the placenta and secreted into both the maternal and fetal circulation. The presence of large molecular weight forms in the placenta suggest that secretion may be constitutive rather that regulated. Placental CRH is bioactive but causes only modest increases in ACTH and cortisol in the pregnant woman because of agonist induced desensitisation of pituitary CRH receptors. CRH concentrations increase exponentially in maternal plasma as gestation advances. Elevated concentrations, compared with gestational age matched controls, occur in patients in preterm labour. The exponential curve describing the CRH increase is shifted to the left in women who will subsequently deliver preterm and to the right in women who will deliver post dates indicating that CRH is linked to a placental clock which determines the length of gestation. Maternal plasma CRH concentrations may be useful in identifying women at high risk of preterm delivery and CRH antagonists may prevent preterm labour. As significant CRH production by the placenta is restricted to primates future research must take into account the species specificity of the mechanisms regulating parturition.
Publisher: Elsevier BV
Date: 08-2008
DOI: 10.1016/J.CYTO.2008.05.008
Abstract: The mechanisms contributing to worsening of asthma during pregnancy have not been well characterized. Both asthma and pregnancy are conditions associated with a skewing of the immune response from T helper (Th) 1 toward a Th2 response. We hypothesise that worsening of asthma during pregnancy may be due to an enhanced production of circulating proinflammatory cytokines and chemokines and this may be modified by the use of inhaled glucocorticoid treatment. Peripheral blood was collected from asthmatic (n=35) and control non-asthmatic patients (n=13) in the third trimester (30-37 weeks) of pregnancy. Fetal blood was collected from the umbilical vein of the placenta after delivery from normal (n=24) and pregnancies complicated by asthma (n=24). Plasma s les were assayed for IL-6, -8, eotaxin and RANTES using conventional ELISA. In addition, a range of Th1 and Th2 cytokines measured using Luminex system. There were no significant differences in the levels of maternal IL-6, IL-8, eotaxin and RANTES between asthmatics and nonasthmatics. The results of this study suggest that the presence of asthma does not result in an enhanced circulation of Th2 related cytokines and chemokines during the third trimester of pregnancy. Furthermore peripheral blood cytokine concentrations appear unaffected by inhaled glucocorticoid treatment. Cord plasma eotaxin concentrations were increased in pregnancies complicated by asthma, compared with control. This is the first study to show increased eotaxin production in the feto-placental unit of asthmatic pregnancies and may be one mechanism by which allergy susceptibility is increased in the offspring of asthmatic women.
Publisher: Bioscientifica
Date: 13-06-2023
DOI: 10.1530/REP-22-0278
Abstract: Placental oxidative stress contributes to both normal and abnormal placentation during pregnancy. This review discusses the potential consequence of oxidative stress-induced placental dysfunction on pregnancies complicated by fetal death and pregnancies with a high risk of fetal death. The placenta is a source of reactive oxygen free radicals due to the oxidative metabolism required to meet the demands of the growing fetus. The placenta has an array of efficient antioxidant defense systems to deal with rising oxidative stress created by free radicals during pregnancy. Properly controlled physiological (low-level) free radical production is a necessary part of cellular signaling pathways and downstream activities during normal placental development however, poorly controlled oxidative stress can cause aberrant placentation, immune disturbances and placental dysfunction. Abnormal placental function and immune disturbances are linked to many pregnancy-related disorders, including early and recurrent pregnancy loss, fetal death, spontaneous preterm birth, preecl sia and fetal growth restriction. This review discusses the role of placental oxidative stress in both normal and pathological settings. Finally, based on previously published work, this review presents multiple lines of evidence for the strong association between oxidative stress and adverse pregnancy outcomes, including fetal death and pregnancies with a high risk of fetal death.
Publisher: Elsevier BV
Date: 02-2006
DOI: 10.1016/J.CHROMA.2005.11.119
Abstract: Clinical and metabolomic investigations of complex human fluids require cost-effective methodologies that can rapidly assess the steroid hormone milieu of in idual s les. The efficiency of quantification of many steroids is limited using immunoassays as these methods can only measure a single component of biological s les and are dependent upon the specificity of the antiserum used in the protocol. In this study, we optimised the solid-phase extraction protocol for the extraction of a range of steroids of varied polarity from estetrol to progesterone from human plasma. The final SPE procedure for efficient extraction of steroids was a washing mixture of 5 ml of 30% methanol and an elution solvent of 2 ml of 100% methanol using 0.5 g C-18 cartridges. This protocol resulted in a high recovery rate, ranging from 85.2 to 99.9% for both the internal standard (7,8-dimethoxyflavone) and steroids of interest. We also improved the separation methodology of our previous work using temperature dependent inclusion chromatography with a mobile phase composition of 35% acetonitrile and 12 mM of beta-cyclodextrin at 29 degrees C. Under these conditions most of the fluid components including estetrol were detected in the first 10 min with progesterone appearing at 43 min. This method is simplistic, inexpensive and reproducible with the capabilities of accurate quantification of steroids. Therefore it could have numerous clinical and metabolomic applications.
Publisher: Wiley
Date: 11-1980
DOI: 10.1111/J.1365-2265.1980.TB03411.X
Abstract: A double blind trial of bromocriptine 7.5 mg daily versus placebo was carried out in ten infertile men. Pretreatment basal plasma prolactin, thyroid stimulating hormone (TSH) testosterone and luteinizing hormone (LH) concentrations were normal, but plasma follicle-stimulating-hormone (FSH) was raised in four in iduals. After 4 months treatment with bromocriptine a significant fall in plasma prolactin was observed (P less than 0.01), both under basal conditions and following thyroid stimulating hormone releasing hormone (TRH). Basal plasma gonadotrophin, testosterone and thyroid stimulating hormone (TSH) concentrations did not alter. No change in sperm density, volume or motility was noted. However an apparent fall in the peak plasma LH (but not FSH) response to gonadotrophin releasing hormone (LHRH) was observed in patients receiving bromocriptine. This reduction in plasma LH responsiveness was significant when compared with the baseline response (P less than 0.05) but failed to reach significance when compared with the placebo response. It is concluded that prolonged bromocriptine therapy in normoprolactinaemic men does not suppress FSH secretion, and any reduction in plasma LH responsiveness to LHRH is not accompanied by a significant fall in plasma testosterone.
Publisher: Springer Science and Business Media LLC
Date: 28-10-2021
DOI: 10.1007/S43032-021-00778-X
Abstract: The pregnant uterus remains relaxed throughout fetal gestation before transforming to a contractile phenotype at term to facilitate birth. Despite ongoing progress, the precise mechanisms that regulate this phenotypic transformation are not yet understood. This knowledge gap limits our understanding of how dysregulation of uterine smooth muscle biology contributes to life-threatening obstetric complications, including preterm birth, and h ers our ability to develop effective therapeutic intervention strategies. Protein acetylation plays a vital role in regulating protein structure, function, and subcellular localization, as well as gene transcription availability through regulating chromatin condensation. Histone deacetylase inhibitors (HDACis) are a class of compounds that block the removal of acetyl functional groups from proteins and, as such, have profound effects on important cellular events, including phenotypic transformation. A large body of data now demonstrates that HDACis have profound effects on pregnant human myometrium. Studies to date show that HDACis operate through both genomic and non-genomic mechanisms to affect myometrial function and phenotype. Interestingly, the effects of HDACis on pregnant myometrium are largely "pro-relaxation," including the direct inhibition of contractile machinery as well as repression of pro-labor genes. The "dual action" effects of HDACis make them a powerful tool for unlocking the regulatory processes that underpin myometrial phenotypic transformation and raises prospects of their therapeutic applications. Here, we review the new insights into human myometrial biology that have garnered through the application of HDACis and explore their potential therapeutic application toward the development of novel preterm birth prevention strategies.
Publisher: The Endocrine Society
Date: 1988
Abstract: The opioid peptide methionine-enkephalin (Met-enkephalin) was measured in plasma and cerebrospinal fluid (CSF) of sheep in which the cisterna magna, carotid artery, and jugular vein were chronically cannulated. Venous blood plasma and CSF were collected before and after stress treatment and in control studies in conscious animals. Plasma and CSF were extracted with octadecylsilica and oxidized, and Met-enkephalin was measured as its Met-sulfoxide derivative by specific RIA. The molecular form of immunoreactive Met-enkephalin was characterized by peptide size exclusion chromatography of an octadecylsilica extract of sheep plasma through Bio-Gel P2, followed by reverse phase liquid chromatography, and was identical to Met-enkephalin and Met-sulfoxide-enkephalin. Insulin-induced hypoglycemia produced an elevation of plasma cortisol and an increase in the plasma concentration of Met-enkephalin. Acute hemorrhage led to an earlier and greater rise in plasma cortisol than that associated with insulin-induced hypoglycemia, but did not increase the concentration of Met-enkephalin in plasma. Neither form of acute stress increased the concentration of Met-enkephalin in CSF. These studies confirm that secretion of Met-enkephalin into blood can be dissociated from stimulation of the pituitary-adrenocortical system. They also show that circulating Met-enkephalin is elevated in conscious sheep during acute hypoglycemic stress, but plasma Met-enkephalin is unlikely to exert effects on the opiate receptors of periaqueductal or spinal nociceptive neurons under these conditions, since it does not enter cerebrospinal fluid in significant amounts.
Publisher: Elsevier BV
Date: 09-1996
DOI: 10.1016/0303-7207(96)03881-6
Abstract: In the anterior pituitary, cGMP is produced in response to a number of stimuli, but intracellular events distal to cGMP production are obscure. Since cGMP-dependent protein kinase (PKG) is a major effector of cGMP actions in other tissues we have determined whether PKG and its specific substrates might be present and responsive to external signals in the ovine anterior pituitary. Photoaffinity labelling with [32P]cGMP revealed a specific 78 kDa protein in ovine anterior pituitary that comigrated with purified bovine lung PKG-I. PKG in protein extracts from anterior pituitary or cultured anterior pituitary cells was enriched by DEAE ion-exchange chromatography and assayed for activity. Both tissue and cultured cells had a relatively high PKG activity by comparison with aortic smooth muscle (known high activity) and brain (known low activity). Subcellular distribution studies showed that in anterior pituitary, aortic and brain, PKG activity was present in both cytosol and triton-extracted membrane fractions, while in platelets the activity was associated with only the membrane fraction. To determine if this PKG might be responsive to extracellular signals an activity ratio assay was used. Incubation of cultured cells with atrial natriuretic peptide (ANP) and sodium nitroprusside, activators of membrane and cytosolic guanylate cyclases respectively, increased the activity of PKG. To determine events distal to PKG activation, a search for potential substrates of PKG was performed. Few substrates were detectable upon addition of purified PKG to tissue lysates due to the high background activity of endogenous protein kinases in the anterior pituitary. However, 19 substrates of PKG were detected in heat-stable and 14 in acid-soluble protein extracts of the anterior pituitary, in which background phosphorylation was almost abolished. After partial purification through Q-Sepharose ion-exchange chromatography some of these proteins were preferentially phosphorylated by addition of PKG-I, while the others were additionally substrates of exogenous cAMP-dependent protein kinase (PKA) or Ca2+ and phospholipid-dependent protein kinase (PKC). A 132-kDa substrate showed an identical phosphopeptide map to a PKG substrate previously described in vascular smooth muscle and platelets. These data demonstrate for the first time the presence of functional PKG activity and multiple PKG substrates in the anterior pituitary where they may play a role in mediating the intracellular actions of cGMP.
Publisher: Springer Science and Business Media LLC
Date: 11-2019
DOI: 10.1186/S12884-019-2550-X
Abstract: Accessibility and utilization of antenatal care (ANC) service varies depending on different geographical locations, sociodemographic characteristics, political and other factors. A geographically linked data analysis using population and health facility data is valuable to map ANC use, and identify inequalities in service access and provision. Thus, this study aimed to assess the spatial patterns of ANC use, and to identify associated factors among pregnant women in Ethiopia. A secondary data analysis of the 2016 Ethiopia Demographic and Health Survey linked with the 2014 Ethiopian Service Provision Assessment was conducted. A multilevel analysis was carried out using the SAS GLIMMIX procedure. Furthermore, hot spot analysis and spatial regressions were carried out to identify the hot spot areas of and factors associated with the spatial variations in ANC use using ArcGIS and R softwares. A one-unit increase in the mean score of ANC service availability in a typical region was associated with a five-fold increase in the odds of having more ANC visits. Moreover, every one-kilometre increase in distance to the nearest ANC facility in a typical region was negatively associated with having at least four ANC visits. Twenty-five percent of the variability in having at least four ANC visits was accounted for by region of living. The spatial analysis found that the Southern Nations, Nationalities and Peoples region had high clusters of at least four ANC visits. Furthermore, the coefficients of having the first ANC visit during the first trimester were estimated to have spatial variations in the use of at least four ANC visits. There were significant variations in the use of ANC services across the different regions of Ethiopia. Region of living and distance were key drivers of ANC use underscoring the need for increased ANC availability, particularly in the cold spot regions.
Publisher: The Endocrine Society
Date: 12-1992
DOI: 10.1210/JCEM.75.6.1464647
Abstract: The human placenta has been implicated as a source of numerous peptide hormones during pregnancy. Since the immunoassay detection of the proopiomelanocortin derived peptide beta-endorphin (beta E) in placental extracts in 1978, it has remained uncertain whether placental beta E immunoreactivity (IR) is 1) secreted into the maternal circulation and 2) opiate receptor active during pregnancy. To elucidate the nature of beta E IR in the placenta, both beta E IR and N-alpha-acetylated beta E (Ac beta E) IR were simultaneously measured in extracts of human pituitaries, placentas, and plasma by two homologous RIAs. Pituitary extracts (n = 6) contained 38 +/- 7 nmol beta E IR per g wet wt tissue (mean +/- SEM), of which only 20 +/- 4 pmol/g were Ac beta E IR. Term placental extracts (n = 19) had 201 +/- 30 fmol/g wet wt total beta E IR and 30 +/- 3 fmol/g wet wt total Ac beta E IR, which comprised 15% of total beta E IR in placental extracts. Total plasma beta E IR rose from 28 weeks gestation (8.5 +/- 0.3 fmol/mL, n = 159) to peak at labor (50 +/- 4 fmol/mL, n = 98 P < 0.01) but total Ac beta E IR was found in only four 28-week (1.7 +/- 0.9 fmol/mL) and 42 labor plasma s les (0.9 +/- 0.1 fmol/mL). Gel filtration chromatography of placental and pituitary extracts showed that while less than 1% of the beta E31-size material was acetylated in the pituitary, up to 60% of the beta E31-size material in placental extracts was acetylated. In pooled third trimester plasma extracts, however, only 4% of the beta E31-size material was acetylated. Furthermore, the ratio of beta E31:beta-lipotropin in pituitary extracts (n = 3) was 0.5 pooled plasma-0.5, and placental extracts (n = 5)-1.2. These data indicate that 1) the placenta extensively N-alpha-acetylates beta E31 destroying its opiate bioactivity while the pituitary does not 2) beta E IR in pregnant women's plasma is similar to pituitary beta E IR, being mostly nonacetylated and similar in size to beta-lipotropin. These findings are consistent with a pituitary source for the elevated plasma beta E IR found during late pregnancy which may, in turn, be a consequence of elevated plasma concentrations of placentally secreted plasma corticotropin-releasing factor IR present during the third trimester.
Publisher: Cambridge University Press (CUP)
Date: 16-05-2019
DOI: 10.1017/S2040174418000302
Abstract: Childhood obesity rates are higher among Indigenous compared with non-Indigenous Australian children. It has been hypothesized that early-life influences beginning with the intrauterine environment predict the development of obesity in the offspring. The aim of this paper was to assess, in 227 mother–child dyads from the Gomeroi gaaynggal cohort, associations between prematurity, Gestation Related-Optimal Weight (GROW) centiles, maternal adiposity (percentage body fat, visceral fat area), maternal non-fasting plasma glucose levels (measured at mean gestational age of 23.1 weeks) and offspring BMI and adiposity (abdominal circumference, subscapular skinfold thickness) in early childhood (mean age 23.4 months). Maternal non-fasting plasma glucose concentrations were positively associated with infant birth weight ( P =0.005) and GROW customized birth weight centiles ( P =0.008). There was a significant association between maternal percentage body fat ( P =0.02) and visceral fat area ( P =0.00) with infant body weight in early childhood. Body mass index (BMI) in early childhood was significantly higher in offspring born preterm compared with those born at term ( P =0.03). GROW customized birth weight centiles was significantly associated with body weight ( P =0.01), BMI ( P =0.007) and abdominal circumference ( P =0.039) at early childhood. Our findings suggest that being born preterm, large for gestational age or exposed to an obesogenic intrauterine environment and higher maternal non-fasting plasma glucose concentrations are associated with increased obesity risk in early childhood. Future strategies should aim to reduce the prevalence of overweight/obesity in women of child-bearing age and emphasize the importance of optimal glycemia during pregnancy, particularly in Indigenous women.
Publisher: Informa UK Limited
Date: 1990
DOI: 10.3109/09513599009024977
Abstract: Plasma corticotropin-releasing hormone immunoreactivity (CRH IR) rises with gestational age in women. In order to investigate the physiological changes of the hormone in pregnant women's urine, CRH IR was measured by radioimmunoassay in urine collected over a 24-hour period, a blood s le and a subsequent single collection of urine after the 24-hour collection (spot urine). Plasma CRH IR in pregnant subjects, 8682.8 +/- 2063.0 pg CRH IR/ml plasma (mean +/- SEM, n = 25), was significantly higher than that in the non-pregnant controls (7.2 +/- 1.6 pg/ml, n = 5 separate t = 4.21, p = 0.0003, d.f. = 24). Similarly, pregnant women had higher spot urine CRH IR - 54.6 +/- 15.5 pg/mumol creatinine (Cr) versus 5.0 +/- 0.5 pg/mumol Cr (separate t = 3.20, p = 0.0038, d.f. = 24.0) - and 24-hour urine CRH IR - 13.7 +/- 1.2 pg/mumol Cr compared with 7.7 +/- 0.8 pg/mumol Cr (separate t = 4.28, p = 0.003, d.f. = 24.4) than the non-pregnant cohort. The difference between urinary excretion of CRH IR as estimated by 24-hour urine (13.7 +/- 1.2 pg/mumol Cr) and spot urine (54.6 +/- 15.5 pg/mumol Cr) indicated that CRH IR in 24-hour urine may be degraded during storage. The weak associations between plasma and 24-hour urine CRH IR of pregnant women (correlation coefficient r = 0.34, p greater than 0.1), and total 24-hour urine and spot urine CRH IR (r = 0.25, p less than 0.1) further indicate CRH degradation. Plasma and spot urinary CRH IR, however, were strongly correlated (r = 0.80, p = 0.001). The total CRH IR excreted as estimated from the spot urine value (0.5 +/- 0.1 micrograms/day) compared with the total filtered load of CRH IR in the pregnant group (1306.9 +/- 324.6 micrograms/day) showed that 99.97% of the filtered CRH IR was reabsorbed or metabolized by the kidneys. Acidic gel chromatography of spot and 24-hour urine s les showed a CRH IR peak at CRH41 standard elution position (Kd = 0.5), indicating that the molecular form in urine is similar to the 41-residue standard. Pregnancy-induced hypertension correlated positively with plasma CRH IR (r = 0.62, p less than 0.001) and spot urine CRH IR (r = 0.46, p less than 0.01), and negatively with parity (r = -0.60, p less than 0.001). Plasma CRH IR and parity also negatively correlated (r = -0.41, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.AJOG.2017.11.567
Abstract: The placenta ages as pregnancy advances, yet its continued function is required for a successful pregnancy outcome. Placental aging is a physiological phenomenon however, there are some placentas that show signs of aging earlier than others. Premature placental senescence and aging are implicated in a number of adverse pregnancy outcomes, including fetal growth restriction, preecl sia, spontaneous preterm birth, and intrauterine fetal death. Here we discuss cellular senescence, a state of terminal proliferation arrest, and how senescence is regulated. We also explore the role of physiological placental senescence and how aberrant placental senescence alters placental function, contributing to the pathophysiology of fetal growth restriction, preecl sia, spontaneous preterm labor/birth, and unexplained fetal death.
Publisher: Springer Science and Business Media LLC
Date: 08-08-2011
Abstract: Preconception and pregnancy dietary intakes can influence the health of future generations. In this study we compared the food intakes of reproductive-aged women by pregnancy status, to current Australian recommendations. Data are from the Australian Longitudinal Study on Women's Health, younger cohort aged 25-30 years in 2003, with self-reported status as pregnant (n = 606), trying to conceive (n = 454), given birth in the last 12 months (n = 829) or other (n = 5597). Diet was assessed using a validated 74-item food frequency questionnaire. Food group servings and nutrient intakes were compared to the Australian Guide to Healthy Eating (AGHE) and Australian Nutrient Reference Values (NRVs). No women met all AGHE food group recommendations. Highest adherence rates [mean (95% CI) servings/day] were for meat [85%, 1.9(1.8-1.9)], fruit [44%, 2.1(2.1-2.2)] and dairy [35%, 1.8(1.8-1.9)], with 14% meeting remaining recommendations. Women who achieved NRVs (folate, iron, calcium, zinc, fibre) for pregnancy, breastfeeding and adult life stages were 1.5%, 3.3% and 13.7%, respectively. Compared to AGHE, women consumed more servings of fruit (4.9 vs 4.0 P = 0.034) and dairy (3.4 vs 2.0 P = 0.006) to achieve pregnancy NRVs more dairy (2.9 vs 2.0 P = 0.001), less fruit (3.9 vs 5.0 P .001) and vegetables (3.4 vs 7.0 P .001) to achieve breastfeeding NRVs more fruit (3.6 vs 3.0 P .001), dairy (2.5 vs 2.0 P .001), meat (1.8 vs 1.5 P = 0.015), less vegetables (3.6 vs 5.0 P .001) to achieve adult NRVs. The AGHE does not align with contemporary diets of Australian women or enable them to meet all NRVs. Current tools to guide food consumption by women during pregnancy require revision.
Publisher: Springer Science and Business Media LLC
Date: 05-2004
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.PLACENTA.2022.07.015
Abstract: Syngnathids (seahorses, pipefishes and seadragons) are among the few vertebrates that display male pregnancy. During seahorse pregnancy, males incubate developing embryos embedded in a placenta within a fleshy brood pouch, before expelling fully developed neonates at parturition. The mechanisms underpinning seahorse parturition are poorly understood. We examined the morphology of the brood pouch using microcomputed tomography and histological techniques, in combination with physiological assays, to examine how male pot-bellied seahorses (Hippoc us abdominalis) control labour. In female-pregnant vertebrates, nonapeptide hormones (such as vasopressin- and oxytocin-like hormones) produce contractions of gestational smooth muscle to produce labour. Histological analysis of the seahorse brood pouch reveals only scattered small smooth muscle bundles in the brood pouch, and in-vitro application of isotocin (a teleost nonapeptide hormone) to the brood pouch do not produce measurable muscle contractions. Micro-computed tomography shows differences in size and orientation of the anal fin assembly between male and female pot-bellied seahorses, and histological analysis reveals large skeletal muscle bundles attached to the anal fin bones at the male brood pouch opening. We conclude that seahorse parturition may be facilitated by contraction of these muscles, which, in combination with body movements, serves to gape open the pouch and expel the neonates. Future biomechanical studies are needed to test this hypothesis.
Publisher: The Endocrine Society
Date: 08-1980
Abstract: TORC1 (target of rapamycin complex) integrates complex nutrient signals to generate and fine-tune a growth and metabolic response. Npr1 (nitrogen permease reactivator) is a downstream effector kinase of TORC1 that regulates the stability, activity, and trafficking of various nutrient permeases including the ammonium permeases Mep1, Mep2, and Mep3 and the general amino acid permease Gap1. Npr1 exerts its regulatory effects on Mep1 and Mep3 via Par32 (phosphorylated after rapamycin). Activation of Npr1 leads to phosphorylation of Par32, resulting in changes in its subcellular localization and function. Here we demonstrate that Par32 is a positive regulator of TORC1 activity. Loss of Par32 renders cells unable to recover from exposure to rapamycin and reverses the resistance to rapamycin of Δ npr1 cells. The sensitivity to rapamycin of cells lacking Par32 is dependent on Mep1 and Mep3 and the presence of ammonium, linking ammonium metabolism to TORC1 activity. Par32 function requires its conserved repeated glycine-rich motifs to be intact but, surprisingly, does not require its localization to the plasma membrane. In all, this work elucidates a novel mechanism by which Npr1 and Par32 exert regulatory feedback on TORC1.
Publisher: Elsevier BV
Date: 06-2021
Publisher: American Astronomical Society
Date: 28-03-2016
Publisher: Japan Epidemiological Association
Date: 2012
Publisher: Elsevier BV
Date: 04-1998
DOI: 10.1016/S0002-9378(98)60503-2
Abstract: We assessed the ability of maternal plasma corticotropin-releasing hormone measurements to predict preterm delivery in the setting of a pilot study comparing transdermal glyceryl trinitrate with standard beta-mimetic therapy for preterm labor and to determine the effect of these tocolytics on maternal plasma corticotropin-releasing hormone concentrations. Twenty-six consecutive patients with preterm labor were randomized to tocolytic treatment with transdermal glyceryl trinitrate (n=13) or intravenous albuterol (n=13). Plasma corticotropin-releasing hormone immunoreactivity levels were higher in women who were delivered within 7 days (41.4+/-13.5 pmol/L) than in those continuing to term (14.2+/-2.4 pmol/L, p=0.011) and were not altered by treatment. Two women in each of the treatment groups delivered within 7 days of the initiation of treatment, two women in the glyceryl trinitrate group were changed to albuterol because of persistence of contractions. Glyceryl trinitrate treatment was associated with significantly fewer maternal side effects. Neither treatment altered umbilical artery Doppler ultrasonographic findings. Transdermal glyceryl trinitrate is better tolerated than intravenous albuterol but may be no more efficacious than albuterol for the treatment of preterm labor. Biologic markers such as plasma corticotropin-releasing hormone levels may be an important method of identifying women at high risk of preterm delivery.
Publisher: Elsevier BV
Date: 02-2020
Publisher: Springer Science and Business Media LLC
Date: 06-2017
DOI: 10.1007/S10555-017-9671-3
Abstract: The significant role of platelets in the protection of tumour cells from immune attack and shear forces and the promotion of tumour cell extravasation from the bloodstream in the process of haematogenous metastasis have been extensively studied. The role of platelets, and in particular platelet membranes, in the promotion of a more metastatic phenotype in tumour cells is a more recent and, therefore, less well-recognised area of research. This review article summarises studies that have focused on the impact of tumour cell interactions with platelets and platelet membranes on tumour cell behaviour in vitro and in vivo. Furthermore, the gene expression changes that occur within tumour cells following contact with platelet membranes are also extensively reviewed. Overall, the interaction of platelet membranes with tumour cells results in a more invasive phenotype and the promotion of epithelial to mesenchymal transition with our own genetic studies revealing that matrix metalloproteinase-1, plasminogen activator inhibitor-1 and interleukin-8 are globally upregulated in a range of tumour cell lines.
Publisher: Public Library of Science (PLoS)
Date: 27-01-2010
Publisher: Wiley
Date: 20-05-2020
Publisher: Informa UK Limited
Date: 2002
DOI: 10.1076/APAB.110.1.146.892
Abstract: Corticotrophs were long thought to be a static, homogeneous population of cells that respond positively to hypothalamic stimulation, are inhibited by glucocorticoid feedback and secrete a single biologically active peptide, ACTH(1-39). Our current understanding is that this is an oversimplification and corticotrophs are a dynamic and more complex group of cells. The biosynthetic precursors of ACTH and other cleavage products of proopiomelanocortin (POMC) have been found to be secreted by anterior pituitary cells, to circulate and to have biological activity. POMC and the biosynthetic intermediate, pro-ACTH, exert activity antagonistic to ACTH(1-39) on glucocorticoid secretion by adrenal cells, and other derivatives of POMC are mitogenic to adrenocortical cells. In terms of responses to hypothalamic and peripheral factors, corticotrophs are functionally heterogeneous. This is reflected in the sensitivity of in idual subtypes of corticotrophs to CRH, vasopressin and glucocorticoids. There is a functional plasticity amongst the various types of corticotrophs. During gestation, in fetal sheep, changes occur in the overall ACTH-secretory responses to CRH relative to vasopressin, the proportions of total corticotrophs that respond to the respective peptides and the average secretory response of in idual cells. Corticotrophs also respond to locally produced pituitary factors. Local actions of leukaemia inhibitory factor are demonstrated by the effects of immunoneutralization of the peptide in pituitary cells. Urocortin and preproTRH(178-199) are locally produced peptides with potent stimulatory and inhibitory actions on corticotrophs, respectively. The specific roles of these peptides are under investigation.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Wiley
Date: 06-11-2007
Publisher: Springer Science and Business Media LLC
Date: 09-06-2020
DOI: 10.1186/S12884-020-03049-W
Abstract: For every neonate who dies, many others experience a near miss event that could have but did not result in death. Neonatal near miss is three to eight times more frequent than neonatal deaths and, therefore, is more useful for assessing the determinants of adverse neonatal outcomes. The aim of this study was to assess the incidence and determinants of neonatal near miss in south Ethiopia. A facility-based prospective study was conducted among 2704 neonates between 12 July to 26 November 2018. The neonates were followed from the time of admission to hospital discharge or seven postpartum days if the newborn stayed in the hospital. The data were collected by interviewer-administered questionnaire and medical record review. Logistic regression was employed to identify the distant, intermediate and proximal factors associated with neonatal near miss. The independent variables were analysed in three hierarchical blocks. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were used to determine the strength of the associations. The incidences of neonatal near miss and neonatal death were 45.1 (95% CI = 37.7–53.8) and 17.4 (95% CI = 13.0–23.3) per 1000 live births, respectively. Of those newborns who experienced neonatal near miss, more than half (59.8%) of their mothers were referred from other health facilities. After adjusting for potential confounders, the odds of neonatal near miss were significantly higher among neonates with a low monthly income ( 79 USD monthly), a birth interval of less than 24 months and where severe maternal complications had occurred. Strategies to improve neonatal survival need a multifaceted approach that includes socio-economic and health-related factors. The findings of this study highlight important implications for policymakers with regard to neonatal near miss. In particular, addressing inequalities by increasing women’s income, promoting an optimal birth interval of 24 months or above through postpartum family planning, and preventing maternal complications may improve newborn survival.
Publisher: Elsevier BV
Date: 07-1999
DOI: 10.1016/S1043-2760(98)00146-5
Abstract: The role of corticotropin-releasing hormone (CRH) in the regulation of pituitary adrenocorticotropin secretion and the stress response is well established. However, in recent years this peptide has been found to serve a number of functions outside the classic neuroendocrine domain. During pregnancy, CRH derived from the placenta is thought to play a crucial role in the regulation of foetal maturation and the timing of delivery, and CRH has also been implicated in the control of foetal-placental bloodflow. Abnormalities of the placental CRH system might be involved in the pathogenesis of preterm labour, foetal growth retardation and pre-ecl sia, which are the three leading causes of perinatal morbidity and mortality in developed countries.
Publisher: IMR Press
Date: 2007
DOI: 10.2741/2113
Abstract: Corticotrophin-releasing hormone (CRH) is the hypothalamic peptide that controls the function of the pituitary-adrenal axis in response to stress. CRH is also expressed abundantly in the human placenta and is present in high concentrations in maternal and fetal plasma during late pregnancy. During pregnancy, CRH derived from the placenta is thought to play a crucial role in the regulation of fetal maturation and the timing of delivery, and CRH has also been implicated in the control of fetal-placental blood flow. Elevated CRH concentrations, as compared with gestational age matched controls, occur in patients in preterm labour. The exponential curve depicting the CRH increase is shifted to the left in women who will subsequently deliver preterm and to the right in women who will deliver post dates. This has led to the suggestion that CRH production is linked to a placental clock which determines the length of gestation. Clinically, maternal plasma CRH concentrations may be useful in identifying women at high risk of preterm delivery and CRH antagonists may be useful in preventing preterm labour. As significant CRH production by the placenta is restricted to primates, future research must take into account the species specificity of the mechanisms regulating parturition. A number of significant gaps remain in our knowledge of the function of this peptide in pregnancy. This review examines the current evidence regarding the role of CRH in human parturition.
Publisher: Springer Science and Business Media LLC
Date: 10-08-2018
Publisher: CSIRO Publishing
Date: 2000
DOI: 10.1071/CH99015
Abstract: Thiazoles, including 2,7-dimethylthiazolo[4,5-d]pyradazine-4-(5H)-thione (4b) and the corresponding 5-phenylthiazolo[4,5-d]pyradazine-4-methylthiol (5a), were synthesized as part of an ongoing investigation into corticotrophin-releasing hormone (CRH) type 1 receptor activity. Subsequent screening indicated the successful discovery of receptor agonists. Assay results indicated a 52 and 3% increase in β-endorphin release after the administration of 100 M (4b) and (5a), respectively. It is believed that this represents the first evidence of this class of compounds displaying CRH type 1 receptor agonist activity.
Publisher: Springer Science and Business Media LLC
Date: 15-11-2017
Publisher: Elsevier BV
Date: 11-1992
DOI: 10.1016/0143-4004(92)90022-L
Abstract: Three inhibitors of the release or effects of endothelium-derived relaxing factor (EDRF), N-nitro-L-arginine, methylene blue and oxyhemoglobin, caused further increases in perfusion pressure during vascular constriction with submaximal concentrations of the thromboxane A2-mimetic, U46619 in fetal vessels of human placental lobules perfused in vitro. The results suggest the EDRF, released during constriction of fetal placental vessels in response to thromboxane A2 receptor stimulation, attenuates the vasoconstrictor response. Hence, impairment of EDRF release or function could contribute to the reduced placental blood flow observed in various disease states associated with increased thromboxane A2 production such as pre-ecl sia.
Publisher: Springer Science and Business Media LLC
Date: 03-2008
DOI: 10.1007/BF03345599
Publisher: Springer Science and Business Media LLC
Date: 07-2005
DOI: 10.1016/J.JSGI.2005.01.024
Abstract: We conducted a comparative proteomic analysis of placental and umbilical cord blood proteins using surface-enhanced laser desorption ionization-time of flight mass spectrometry (SELDI-TOF MS) to examine the associations among asthma, fetal gender, and protein profiles. Placental tissue and umbilical vein plasma were collected from 10 healthy and 20 asthmatic women. Placental proteins were extracted using phosphate-buffered saline containing protease inhibitors. S les were applied to the surfaces of strong anion exchange (SAX2), weak cation exchange (WCX2) and immobilized metal affinity capture (IMAC-Cu(2+)) chips. Mass analysis was conducted using a Ciphergen Protein Biology System IIc (Freemont, CA), and differences in in idual peak intensities between groups were determined. Fourteen placental peaks were significantly different between asthmatic and non-asthmatic women (seven more highly expressed and seven less highly expressed). Ten umbilical cord blood peak differences were identified, with four peaks more highly expressed and six peaks less highly expressed in asthmatics. Four placental and three umbilical cord blood proteins differed significantly between male and female fetuses. Two placental and five umbilical cord blood peaks were specifically increased in a subgroup of s les collected from asthmatic women who did not use inhaled glucocorticoids and were pregnant with a female fetus, a group previously found to have altered placental function. This study demonstrates the abilities of the SELDI technique as a tool for protein profiling in tissue or plasma. Further work to positively identify the candidate peptides found in this study may provide a greater understanding of the placental mechanisms leading to alterations in fetal growth in patients with bronchial asthma.
Publisher: Springer Science and Business Media LLC
Date: 17-06-2014
DOI: 10.1038/NCOMMS5108
Abstract: Human ether-a-go-go-related gene (hERG) potassium channels determine cardiac action potential and contraction duration. Human uterine contractions are underpinned by an action potential that also possesses an initial spike followed by prolonged depolarization. Here we show that hERG channel proteins (α-conducting and β-inhibitory subunits) and hERG currents exist in isolated patch-cl ed human myometrial cells. We show that hERG channel activity suppresses contraction litude and duration before labour, thereby facilitating quiescence. During established labour, expression of β-inhibitory protein is markedly enhanced, resulting in reduced hERG activity that is associated with an increased duration of uterine action potentials and contractions. Thus, changes in hERG channel activity contribute to electrophysiological mechanisms that produce contractions during labour. We also demonstrate that this system fails in women with elevated BMI, who have enhanced hERG activity as a result of low β-inhibitory protein expression, which likely contributes to the weak contractions and poor labour outcomes observed in many obese women necessitating caesarean delivery.
Publisher: Oxford University Press (OUP)
Date: 12-10-2019
Abstract: In this paper, we describe the International Pulsar Timing Array second data release, which includes recent pulsar timing data obtained by three regional consortia: the European Pulsar Timing Array, the North American Nanohertz Observatory for Gravitational Waves, and the Parkes Pulsar Timing Array. We analyse and where possible combine high-precision timing data for 65 millisecond pulsars which are regularly observed by these groups. A basic noise analysis, including the processes which are both correlated and uncorrelated in time, provides noise models and timing ephemerides for the pulsars. We find that the timing precisions of pulsars are generally improved compared to the previous data release, mainly due to the addition of new data in the combination. The main purpose of this work is to create the most up-to-date IPTA data release. These data are publicly available for searches for low-frequency gravitational waves and other pulsar science.
Publisher: Elsevier BV
Date: 1999
Publisher: Elsevier BV
Date: 11-2012
Abstract: The prenatal environment can induce permanent changes in offspring phenotype. Thinness at birth is associated with adult risk of cardiometabolic disease. The objective was to investigate the association between maternal nutrition during pregnancy and intrauterine development of fetal body composition. We used prospective data from 179 Australian women with singleton pregnancies from the Women and Their Children's Health Study. A validated food-frequency questionnaire was used at 18-24 wk and 36-40 wk of gestation to quantify maternal diet during the previous 3 mo of pregnancy. Fetal body-composition measurements were ascertained from abdominal and midthigh sites by ultrasound performed at 19, 25, 30, and 36 wk. The subcutaneous fat area at each site was calculated by subtracting the lean/visceral area from the total area. In linear mixed-model regressions, maternal intakes of protein (b = -0.13 P = 0.04) and starch (b = 0.10 P = 0.02) and the protein:carbohydrate ratio (b = -3.61 P = 0.02) were associated with the percentage of abdominal fat, whereas SFA (b = 0.27 P = 0.04) and PUFA (b = -0.48 P = 0.03) were associated with the percentage of midthigh fat. Response surfaces for fetal adiposity were maximized at different macronutrient intakes. Abdominal fat was highest with low protein intakes ( 40% of energy), and low carbohydrate (<40% of energy) intakes. Fetal body composition may be modifiable via nutritional intervention in the mother and thus may play an important role in influencing the offspring's risk of future disease.
Publisher: Oxford University Press (OUP)
Date: 04-1993
Abstract: To investigate the dynamic relationships among corticotropin-releasing hormone (CRH), β-endorphin (βEP), cortisol and obstetric events during pregnancy, blood s les were collected from 193 women at 28 weeks, 38 weeks, during labour and on the second postnatal day. Cord blood at delivery was also obtained. We found that: (1) Maternal plasma CRH, βEP and cortisol rose from 28 to 38 weeks. (2) During the third trimester maternal plasma CRH and βEP were correlated (r=0.30, p .001). (3) During labour, no correlations were found among maternal plasma CRH, βEP and cortisol. (4) Maternal CRH at labour and the duration of labour were not correlated. (5) Maternal plasma CRH tended to be higher in women who delivered early (more than seven days prior to estimated date of confinement [EDC]) relative to those who were on time (within seven days' EDC) or late (greater than seven days after EDC). (6) CRH in maternal plasma at labour and cord blood were correlated (r = 0.29, p .05) as were maternal and fetal βEP (r=0.43, p .001). (7) Fetal obstetric difficulty was correlated with fetal βEP (r=0.54, p .001). Our findings support the hypothesis that maternal plasma CRH regulates maternal βEP during the third trimester, but other factors are involved during labour and in response to maternal obstetric stress.
Publisher: Wiley
Date: 25-06-2018
DOI: 10.1111/CEN.13763
Abstract: The aim of this study was to determine whether there has been a change in the mean age and age-standardized incidence of minimal trauma hip fractures in the Newcastle and Lake Macquarie population of Australia between 1998 and 2015. Patients with neck of femur fractures over 50 who presented to the regional referral centre were retrospectively identified using the ICD-9 and ICD-10 coding system. There were 233 and 308 eligible patients in 1998 and 2015, respectively. For females, the mean age for hip fracture of 83.2 years in 1998 was not significantly different from the mean age of 84.5 years in 2015 (P = .16). For males, the mean age for hip fracture was significantly older at 84.6 years in 2015 compared to 80.4 years in 1998 (P = .005). For females, the decrease in the rate of hip fracture from 1998 to 2015 was 13% and was weakly statistically significant (IRR = 0.86, P = .05). For males, there was a statistically significant decrease in the rate of hip fractures from 1998 to 2015 by 33% (IRR = 0.67, P = .001). Our study shows a decrease in age-standardized rates of hip fractures for men and women and suggests that men are demonstrating a greater improvement in bone health compared to women.
Publisher: Springer Science and Business Media LLC
Date: 15-04-2020
DOI: 10.1007/S00467-020-04554-Y
Abstract: We carried out a study to determine the impact of prematurity on kidney development in the first 2 years of life. In this prospective study, extremely preterm neonates (gestation 28 weeks) were recruited and underwent assessments at 6, 12, and 24 months of age. A cohort of neonates born term were also recruited and followed up for 24 months. The primary outcomes measured in this study were total kidney volume (TKV) and estimated glomerular filtration rate (eGFR) albuminuria and blood pressure measurements (all provided as mean (standard deviation)) were the secondary outcomes. Fifty-three premature and 31 term neonates (control) were recruited. At the age of 24 months (corrected age), infants born preterm had significantly smaller TKV (56.1 (9.4) vs. 64.8 (10.2) mL P = 0.006). There was no difference in eGFR. These preterm infants were smaller (11.25 (1.53) vs. 12.9 (1.8) kg P = 0.002) and shorter (83.8 (3.0) vs. 86.3 (3.4) cm P = 0.02) when compared with the control group. At 6, 12, and 18 months respectively, preterm infants had, relative to their height, significantly smaller kidney volumes (0.54 (0.1) vs. 0.59 (0.1) mL/cm, P = 0.05 0.61 (0.1) vs.0.71 (0.1) mL/cm, P = 0.003 and 0.67 (0.1) vs.0.76 (0.1) mL/cm, P = 0.006). Relative to body length, TKV in premature infants is smaller. Since length reflects adult body proportions more accurately than BSA, TKV to height ratio may be a more important measure in the child. Despite smaller TKV (and therefore fewer nephrons), infants born prematurely achieve similar eGFRs in the first 24 months of life, probably due to single-nephron hyperfiltration.
Publisher: Elsevier BV
Date: 12-1985
DOI: 10.1016/0006-291X(85)90954-4
Abstract: To determine whether peptides derived from the N-terminus of the corticotropin/melanotropin/endorphin precursor, pro-opiomelanocortin, are released into blood in response to acute haemorrhagic stress, we examined the effect of haemorrhage on plasma concentrations of immunoreactive gamma 3-melanotropin, beta-endorphin and cortisol. Plasma concentrations of immunoreactive gamma 3-melanotropin (mean +/- SEM) increased within 30 min of haemorrhage from 71.1 +/- 10.4 to 106.8 +/- 6.3 fmol/mL (p less than 0.01) and plasma cortisol increased from 16.2 +/- 3.8 to 85.9 +/- 22.4 pmol/mL (p less than 0.025). The changes in plasma immunoreactive gamma 3-melanotropin and beta-endorphin were positively correlated (p less than 0.025). This study shows that peptides derived from the N-terminus of pro-opiomelanocortin are co-secreted with the C-terminal peptide beta-endorphin during acute haemorrhagic stress in sheep.
Publisher: Elsevier BV
Date: 05-1987
DOI: 10.1016/S0950-351X(87)80070-8
Abstract: The opioid peptides beta-endorphin and [met]enkephalin are present in the peripheral circulation. Plasma beta-endorphin originates from the pituitary gland and its cosecretion with ACTH is stimulated by a variety of noxious stimuli. Although the adrenal medulla contains high concentrations of [met]enkephalin-containing polypeptides which are costored with catecholamines, and although the adrenal gland appears to secrete [met]enkephalin into the adrenal vein, the relative adrenal contribution to plasma [met]enkephalin appears to be negligible. Plasma concentrations of immunoreactive [met]enkephalin may be increased by insulin and by endotoxic shock, but they are not significantly altered by acute haemorrhagic stress nor by surgical stress. Thus blood plasma concentrations of beta-endorphin, but not of [met]enkephalin, are generally increased during acute stress. The physiological significance of endogenous opioids in the circulation is not known. It is unlikely that transient increases in the concentrations of opioid peptides in peripherally circulating blood modulate nociception, since the peptides do not enter ventricular cerebrospinal fluid in detectable amounts under these conditions. Recent evidence has raised the possibility that circulating opioids may be involved in regulating blood glucose and in activating the immune system. It is also possible that circulating beta-endorphin and related polypeptides have non-opioid actions on a variety of peripheral tissues.
Publisher: Springer Science and Business Media LLC
Date: 26-06-2018
Publisher: Elsevier BV
Date: 11-1991
DOI: 10.1016/0140-6736(91)92152-R
Abstract: Infantile Tay-Sachs disease (TSD) is caused by mutations in the HEXA gene that result in the complete absence of beta-hexosaminidase A activity. It is well known that an elevated frequency of TSD mutations exists among Ashkenazi Jews. More recently it has become apparent that elevated carrier frequencies for TSD also occur in several other ethnic groups, including Moroccan Jews, a subgroup of Sephardic Jews. Elsewhere we reported an in-frame deletion of one of the two adjacent phenylalanine codons at position 304 or 305 (delta F304/305) in one HEXA allele of a Moroccan Jewish TSD patient and in three obligate carriers from six unrelated Moroccan Jewish families. We have now identified two additional mutations within exon 5 of the HEXA gene that account for the remaining TSD alleles in the patient and carriers. One of the mutations is a novel C-to-G transversion, resulting in a replacement of Tyr180 by a stop codon. The other mutation is a G-to-A transition resulting in an Arg170-to-Gln substitution. This mutation is at a CpG site in a Japanese infant with Tay-Sachs disease and was described elsewhere. Analysis of nine obligate carriers from seven unrelated families showed that four harbor the delta F304/305 mutation, two the Arg170----Gln mutation, and one the Tyr180----Stop mutation. We also have developed rapid, nonradioactive assays for the detection of each mutation, which should be helpful for carrier screening.
Publisher: American Physiological Society
Date: 15-03-2013
DOI: 10.1152/AJPCELL.00161.2012
Abstract: The degree of phosphorylation of myosin light chain 20 (MLC20) is a major determinant of force generation in smooth muscle. Myosin phosphatases (MPs) contain protein phosphatase (PP) 1 as catalytic subunits and are the major enzymes that dephosphorylate MLC20. MP regulatory targeting subunit 1 (MYPT1), the main regulatory subunit of MP in all smooth muscles, is a key convergence point of contractile and relaxatory pathways. Combinations of regulatory mechanisms, including isoform splicing, multiple phosphorylation sites, and scaffolding proteins, modulate MYPT1 activity with tissue and agonist specificities to affect contraction and relaxation. Other members of the PP1 family that do not target myosin, as well as PP2A and PP2B, dephosphorylate a range of proteins that affect smooth muscle contraction. This review discusses the role of phosphatases in smooth muscle contractility with a focus on MYPT1 in uterine smooth muscle. Myometrium shares characteristics of vascular and other visceral smooth muscles yet, during healthy pregnancy, undergoes hypertrophy, hyperplasia, quiescence, and labor as physiological processes. Myometrium presents an accessible model for the study of normal and pathological smooth muscle function, and a better understanding of myometrial physiology may allow the development of novel therapeutics for the many disorders of myometrial physiology from preterm labor to dysmenorrhea.
Publisher: Springer Science and Business Media LLC
Date: 05-11-2011
DOI: 10.1007/S10995-011-0904-8
Abstract: The objective of this study is to describe the fetal phenotype in utero and its associations with maternal pre-pregnancy weight and gestational weight gain. This prospective longitudinal cohort included 179 Australian women with singleton pregnancies. Serial ultrasound measurements were performed at 19, 25, 30 and 36 (±1) weeks gestation and maternal anthropometry were collected concurrently. The ultrasound scans included the standard fetal biometry of head circumference, biparietal diameter, abdominal circumference, and femur length, and body composition at the abdomen and mid-thigh, including fat and lean mass cross-sectional areas. Maternal gestational weight gain was compared to current clinical guidelines. The participants had an average of 3.7 ± 0.8 scans and birth data were available for 165 neonates. Fifty four per cent of the cohort gained weight in excess of current recommendations, according to pre-pregnancy body mass index (BMI). Maternal gestational weight positively predicted fetal abdominal circumference (P 0.029) and lean abdominal mass area (P 0.046) in linear mixed model regression analysis, adjusted for known and potential confounders. At any pre-pregnancy BMI gaining weight above the current recommendations resulted in a larger fetus according to standard biometry, because of significantly larger lean muscle mass at the abdomen (P 0.024) and not due to an increase in fat mass (P 0.463). We have demonstrated the importance of maternal weight gain, independent of pre-pregnancy BMI, to support the growth of a large but lean fetus. Prenatal counselling should focus on achieving a healthy BMI prior to conception so that gestational weight gain restrictions can be minimised.
Publisher: Bioscientifica
Date: 07-2005
DOI: 10.1677/JOE.1.06030
Abstract: Females have a significantly greater life expectancy than males, which in part may be due to the cardio-protective effects of the female sex hormone, estrogen, on vascular function. However, the sex-specific mechanisms contributing to these differences are complex and not fully understood. Previously we have reported that corticotropin-releasing hormone (CRH) has potent dilator effects in the female skin circulation via mast cell degranulation. Furthermore the dilator response to CRH was more enhanced in females than in age-matched males, suggesting that estrogens may be involved. In this study we examined whether CRH-induced dilation and endothelial cell-dependent dilation in the skin circulation of pre-menopausal females were associated with changes in estrogen during the menstrual cycle. CRH-induced dilation (1 nM) was enhanced in the presence of high circulating concentrations of estrogen and a positive correlation was identified between CRH-induced dilation and plasma estrogen concentrations. Endothelial cell-dependent dilation was examined using acetylcholine. Acetylcholine-induced dilation (1 nM) was not correlated with circulating concentrations of estrogen. These data suggest the variation in CRH-induced dilation in the skin microvasculature during the menstrual cycle may be due to estrogenic effects on mast cell function and not due to direct changes in endothelial cell function.
Publisher: Elsevier BV
Date: 08-2002
DOI: 10.1016/S0303-7207(02)00218-6
Abstract: Glucocorticoids inhibit corticotrophin releasing hormone (CRH) production in the hypothalamus but stimulate production from the placenta. We have sought to identify the key elements regulating the CRH gene. Mouse pituitary tumour-derived cells (AtT20 cells) were used in deletion and mutational analyses of the CRH promoter. Two cAMP responsive elements were identified: (I) a consensus cAMP response element (CRE) and (II) a previously unrecognised caudal-type homeobox response element (CDXRE). Glucocorticoids inhibit only the component of cAMP-stimulation occurring via the CRE through an action involving a negative glucocorticoid response element (nGRE). We also identified two regions that, in the absence of the nGRE, can be stimulated by glucocorticoids: (I) the CRE and (II) a region between -213 and -99 bps. Electrophoretic mobility shift assays (EMSAs) identified binding of the transcription factors CREB and Fos at the CRE in AtT20 cells while CREB and cJun were detected in placental cells. Tissue specific expression of transcription factors may mediate regulation of the CRH gene.
Publisher: Elsevier
Date: 2020
Publisher: Wiley
Date: 21-10-2018
DOI: 10.1111/AOGS.13464
Abstract: The aim of this study was to examine the association between plasma hormone concentrations, cervical length, and preterm delivery in twin pregnancies, including the effect of progesterone treatment. This study included 191 women pregnant with twins from a randomized placebo-controlled trial. A baseline blood s le was collected at 18-24 weeks before treatment with vaginal progesterone (n = 95) or placebo pessaries (n = 96), and 167 (87.4%) women had a second s le collected after 4-8 weeks of treatment. At baseline, 155 (81.2%) women had their cervical length measured. Progesterone, estradiol, and unconjugated estriol concentration was measured, and the association between hormone concentrations, cervical length, and gestational age at delivery was examined. Hormone concentrations were compared in the placebo and progesterone group. Statistical analysis included Spearman's rho, Mann-Whitney U test, Cuzick's test for trends, and linear regression analyses. A short cervical length was associated with preterm delivery. Cervical length and hormone concentrations were not associated (Spearman's rho progesterone -.05, estradiol .04, estriol .08). Decreasing gestational age at delivery was associated with higher progesterone and estradiol concentrations at baseline (P trend progesterone 0.04, estradiol 0.02) but not in the second s le or in the weekly change between s les. Progesterone treatment did not increase the progesterone concentration. Plasma concentrations of progesterone, estradiol, and unconjugated estriol at 18-24 weeks are not associated with cervical length or preterm delivery in twin pregnancies. Vaginal progesterone treatment does not increase the circulating progesterone concentration in twin pregnancies. Cervical length, but not hormone concentration, is predictive of preterm delivery in twin gestations.
Publisher: The Endocrine Society
Date: 06-1986
Abstract: The effects of acute hemorrhagic stress on the concentrations of immunoreactive beta-endorphin (IR beta EP) in cerebrospinal fluid (CSF) and blood plasma were investigated in conscious sheep in which the cisterna magna, a carotid artery, and a jugular vein were chronically cannulated. Serial s les of CSF and jugular venous blood were collected before and after acute arterial hemorrhage and in control experiments. Basal concentrations of IR beta EP were higher in plasma than in CSF. Plasma concentrations of cortisol and IR beta EP increased within 45 min of the commencement of hemorrhage and returned to near baseline levels within 2.25 h. The concentrations of cortisol and IR beta EP in plasma observed after hemorrhage were significantly different from those observed in controls (analysis of variance). Neither the molar nor the relative changes from initial concentrations of IR beta EP in CSF were significantly different between hemorrhage-stressed and controls by analysis of variance. These results show that hemorrhagic stress in conscious sheep elevates concentrations of IR beta EP in plasma but not in CSF, indicating that pituitary beta EP secreted into blood does not enter CSF in significant amounts.
Publisher: Wiley
Date: 04-1985
DOI: 10.1038/ICB.1985.17
Abstract: A method of cannulating the cisterna magna of sheep is described. Successful cannulations were achieved in 15 of 17 attempts (88%). Mean cannula patency was 13.9 days (range 7-20). Using these cannulas, it was possible to obtain s les of cerebrospinal fluid (CSF) in large volumes (4-8 ml) and remove 20-30 ml of CSF over a 5 h period. This technique allows access to the CSF of an animal large enough for the removal of s les of CSF of sufficient size to detect materials present at very low concentrations.
Publisher: BMJ
Date: 28-09-2012
DOI: 10.1136/BJOPHTHALMOL-2011-300950
Abstract: The objectives of this study were to measure optic disc size in full term infants and to determine whether this value is influenced by sex or birth weight. Retinal images from a cohort of full term infants admitted to a tertiary perinatal centre were obtained using a retinal camera. Optic disc size was measured by carefully delineating the outline with a cursor using image analysis software. MEDLINE was then systematically searched to compare the data with other published articles. 35 images of left and right eyes from 35 infants were assessed. An image from one eye per patient was then chosen for analysis. The following results were found: mean birth weight 3050±706 g mean gestation 38.9±1.4 weeks. Mean optic disc area was 1.26±0.23 mm(2) mean vertical diameter was 1.37±0.15 mm and mean horizontal diameter was 1.14±0.12 mm. The vertical diameter of the optic disc was significantly longer than the horizontal diameter (p<0.0001). Birth weight and sex did not influence the size of the optic disc in term infants. There were no differences in optic disc measurements between male and female infants and between low birth weight and normal birth weight infants.
Publisher: Elsevier BV
Date: 08-2011
DOI: 10.1016/J.BBI.2011.03.014
Abstract: Stressful events during the perinatal period in both humans and animals have long-term consequences for the development and function of physiological systems and susceptibility to disease in adulthood. One form of stress commonly experienced in the neonatal period is exposure to bacterial and viral infections. The current study investigated the effects of live Chlamydia muridarum bacterial infection at birth followed by re-infection in adulthood on hippoc al glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) and stress response outcomes. Within 24 h of birth, neonatal mice were infected intranasally with C. muridarum (400 inclusion-forming units [ifu]) or vehicle. At 42 days, mice were re-infected (100 ifu) and euthanized 10 days later. In males, infection in adulthood alone had the most impact on the parameters measured with significant increases in GR protein compared to adult infection alone and significant increases MR protein and circulating corticosterone compared to other treatment groups. Neonatal infection alone induced the largest alterations in the females with results showing reciprocal patterns for GR protein and TH protein. Perinatal infection resulted in a blunted response following adult infection for both males and females across all parameters. The present study demonstrates for the first time that males and females respond differently to infection based on the timing of the initial insult and that there is considerable sex differences in the hippoc al phenotypes that emerge in adulthood after neonatal infection.
Publisher: Oxford University Press (OUP)
Date: 16-01-2014
Abstract: Progesterone regulates female reproductive function predominantly through two nuclear progesterone receptors (PRs), PR-A and PR-B. During human parturition myometrial PR expression is altered to favour PR-A, which activates pro-labour genes. We have previously identified histone H3 lysine 4 trimethylation (H3K4me3) as an activator of myometrial PR-A expression at labour. To further elucidate the mechanisms regulating PR isoform expression in the human uterus at labour, we have (i) determined the methylation profile of the cytosine-guanine dinucleotides (CpG) island in the promoter region of the PR gene and (ii) identified the histone-modifying enzymes that target the H3K4me3 mark at the PR promoters in term and preterm human myometrial tissues obtained before and after labour onset. Bisulphite sequencing showed that despite overall low levels of PR CpG island methylation, there was a significant decrease in methylated CpGs with labour in both preterm (P < 0.05) and term (P < 0.01) groups downstream of the PR-B transcription start site. This methylation change was not associated with altered PR-B expression, but may contribute to the increase in PR-A expression with labour. Chromatin immunoprecipitation revealed that the histone methyltransferase, SET and MYND domain-containing protein 3 (SMYD3), bound to the PR gene at significantly higher levels at the PR-A promoter compared with the PR-B promoter (P < 0.010), with no labour-associated changes observed. The H3K4 demethylase, Jumonji AT-rich interactive domain 1A (JARID1A), also bound to the PR-A, but not to the PR-B promoter prior to term labour, and decreased significantly at the onset of labour (P = 0.014), providing a mechanism for the previously reported increase in H3K4me3 level and PR-A expression with labour. Our studies suggest that epigenetic changes mediated by JARID1A, SMYD3 and DNA methylation may be responsible, at least in part, for the functional progesterone withdrawal that precipitates human labour.
Publisher: Elsevier BV
Date: 2019
Publisher: Springer Science and Business Media LLC
Date: 06-2013
Abstract: To determine delivery outcome in women undergoing induction of labor for postdate pregnancy in relation to fetal gender. A total of 365 nulliparous and 127 multiparous women carrying singleton postdate pregnancies with unfavorable cervix were enrolled. Clinical characteristics and delivery outcome were analyzed in relation to fetal gender. Women carrying male fetuses showed higher rate of caesarean section than those carrying females, in both nulliparous and multiparous women. Moreover, women carrying male fetuses presented more frequently with (i) interval between induction of labor and delivery >24 hours (P < .0002) (ii) augmentation of labor after cervical ripening (P < .0391) (iii) meconium-stained liquor (P< .0126) and (iv) higher neonatal weight (P < .0011) than those carrying females. Male fetuses are more likely to be associated with higher rates of cesarean section. In maternal fetal medicine, gender differences may add prognostic information on the delivery outcome in women induced for postdate pregnancy.
Publisher: The Endocrine Society
Date: 28-08-2008
DOI: 10.1210/EN.2008-0593
Abstract: For a successful human pregnancy, the phasic smooth muscle of the myometrium must remain quiescent until labor. Activation of cAMP/cAMP-dependent protein kinase A (PKA) pathways contributes to this quiescence. The small heat-shock protein 20 (HSP20) is a target of PKA, and phosphorylated HSP20 (pHSP20) modulates relaxation of tonic vascular smooth muscle via interaction with actin, independent of myosin dephosphorylation. Our objective was to determine whether relaxation in human myometrium is associated with changes in phosphorylation of HSP20. Myometrium was obtained at elective cesarean. Elevating cAMP with forskolin or rolipram (a phosphodiesterase inhibitor) caused substantial relaxation of spontaneously contracting human myometrial strips, of 92 ± 4% (mean ± sem, n = 10) and 84 ± 7% (n = 6), respectively. Subsequent two-dimensional electrophoresis with immunoblotting of strip extracts showed a significant 2.6- and 2.1-fold increase in phosphorylated HSP20 (pHSP20) after forskolin (P & 0.01 n = 5) or rolipram treatment (P & 0.05 n = 4). Noncyclic-nucleotide-mediated relaxation, induced by the calcium channel blocker nifedipine, did not alter pHSP20. Inhibition of PKA with H89 significantly attenuated rolipram-induced relaxation (P & 0.01 n = 4), and partially reduced rolipram-stimulated pHSP20. Total and pHSP20 protein was unchanged in term laboring and nonlaboring myometria. Coimmunoprecipitation studies revealed a specific association of HSP20 with α-smooth muscle actin and HSP27, a key regulator of actin filament dynamics. Finally, coimmunofluorescence demonstrated moderate colocalization of HSP20 with α-smooth muscle actin in the cytoplasm of laboring myometria. Our data support a novel role for pHSP20 in the modulation of cyclic-nucleotide-mediated myometrial relaxation, through interaction with actin. pHSP20 represents an important new target for future tocolytic therapy.
Publisher: Wiley
Date: 08-2008
Publisher: Informa UK Limited
Date: 02-2022
DOI: 10.2147/IJWH.S341912
Publisher: Wiley
Date: 13-11-2019
DOI: 10.1111/AOGS.13491
Publisher: Cambridge University Press (CUP)
Date: 15-04-2016
DOI: 10.1017/S204017441600009X
Abstract: Indigenous Australians have high rates of chronic diseases, the causes of which are complex and include social and environmental determinants. Early experiences in utero may also predispose to later-life disease development. The Gomeroi gaaynggal study was established to explore intrauterine origins of renal disease, diabetes and growth in order to inform the development of health programmes for Indigenous Australian women and children. Pregnant women are recruited from antenatal clinics in Tamworth, Newcastle and Walgett, New South Wales, Australia, by Indigenous research assistants. Measures are collected at three time points in pregnancy and from women and their children at up to eight time points in the child’s first 5 years. Measures of fetal renal development and function include ultrasound and biochemical biomarkers. Dietary intake, infant feeding and anthropometric measurements are collected. Standardized procedures and validated tools are used where available. Since 2010 the study has recruited over 230 women, and retained 66 postpartum. Recruitment is ongoing, and Gomeroi gaaynggal is currently the largest Indigenous pregnancy-through-early-childhood cohort internationally. Baseline median gestational age was 39.1 weeks (31.5–43.2, n =110), median birth weight was 3180 g (910–5430 g, n =110). Over one third (39.3%) of infants were admitted to special care or neonatal nursery. Nearly half of mothers (47.5%) reported tobacco smoking during pregnancy. Results of the study will contribute to knowledge about origins of chronic disease in Indigenous Australians and nutrition and growth of women and their offspring during pregnancy and postpartum. Study strengths include employment and capacity-building of Indigenous staff and the complementary ArtsHealth programme.
Publisher: Wiley
Date: 27-02-2009
Abstract: Human myometrium undergoes a major phenotypic change at labour likely involving modifications to key regulatory proteins. In some cases, the myometrium fails to activate normally and medical intervention is required to induce labour. In this study, 2-D DIGE was used to examine changes in the myometrial proteome at the time of spontaneous (SL) and induced labour (IL). Proteomic profiles of nonlabouring term myometria (NL, n = 6) were quantitatively compared to SL (n = 6) and prostaglandin/oxytocin-IL term myometria (n = 6). In SL s les, 23 differentially expressed protein spots were detected (9 increased/14 decreased compared to NL, p<0.05). In IL s les, 59 differentially expressed spots were observed (13 increased/46 decreased compared to NL). Comparison of SL and IL proteomes revealed 69 differentially expressed proteins (7 increased/62 decreased). Two proteins consistently decreased in SL and IL s les were identified as transgelin (1.98- and 1.97-fold decrease in SL and IL, respectively) and αB-crystallin (3.27- and 2.49-fold decrease). Levels of desmin and cytosolic phospholipase A2 β were decreased 2.9- and 2.65-fold, respectively only in IL s les. Our results show human labour is accompanied by general downregulation of specific myometrial proteins. Differences exist between SL and IL myometrial proteomes indicating ergence of underlying processes and highlighting the importance of distinguishing these groups in future studies of parturition. Our findings underscore the utility of discovery approaches in investigations of organ-wide protein changes that underlie discrete physiological events including human labour.
Publisher: Wiley
Date: 02-1990
DOI: 10.1111/J.1365-2826.1990.TB00399.X
Abstract: Abstract Human placental extracts fractionated with Sephadex G-50 produced three peaks of corticotrophin-releasing hormone immunoreactivity, a large molecular weight peak (M(r)30,000), an intermediate peak (4,758 < M(r) < 10,000) and a low molecular weight peak coeluting with the 41-residue hormone. All three peaks of immunoreactivity stimulated the release of beta-endorphin-like immunoreactivity from ovine pituitary cells superfused in vitro. No response was observed from unstimulated cells superfused in parallel. Gel chromatography indicated that intermediate and small molecular weight forms of human corticotrophin-releasing hormone immunoreactivity remained intact after contact with the ovine pituitary cells, whereas the large molecular weight material dissociated to produce 41-residue hormone immunoreactivity. The secreted beta-endorphin immunoreactivity was shown by gel chromatography to comprise both beta-lipotrophin-like and the 31-residue beta-endorphin-like immunoreactivity. The data show that the intermediate and low molecular weight forms of placental corticotrophin-releasing hormone immunoreactivity are bioactive and suggest that the intermediate form is a hormone precursor, possibly procorticotrophin-releasing hormone(125-196), and the small form is identical to the hypothalamic hormone. The results with the larger molecular weight material indicate that it is likely to be a complex of the mature 41-residue hormone and a binding protein.
Publisher: Informa UK Limited
Date: 1997
Publisher: SAGE Publications
Date: 03-10-2012
DOI: 10.5301/JN.5000220
Abstract: Low birth weight (LBW), defined as birth weight below 2,500 g, is an important risk factor for the development of hypertension and renal disease in adult life. LBW is associated with a reduced nephron number, which results in hyperfiltration. The objective of this study was to compare the glomerular filtration rates (GFRs) of LBW and normal-birth-weight (NBW) term infants relative to their kidney volumes. Term infants (born after 37 weeks of gestation) who had been admitted to Townsville Hospital's neonatal unit were recruited for this study. Serum cystatin C was used to calculate gfr. a kidney ultrasound was used to measure renal volume. all assessments were performed during the first week of life. Data from 39 infants (17 male, 22 female 13 LBW, 26 NBW) were analyzed. There were no significant differences in the median cystatin C (1.36 mg/L, inter quartile range [IQR] = 1.12 - 1.41, vs. 1.17 mg/L, IQR = 1.10 - 1.39 p = 0.39) and gestational age. There was no significant difference in the median GFR (53.0 ml/min per 1.73 m2, IQR = 50.8-66.9, vs. 63.2 ml/min per m2, IQR = 51.8-69.5 p = 0.39) between LBW and NBW infants, but LBW infants had smaller total renal volume compared with NBW infants (18.0 ± 4.7 mL vs. 24.4 ± 6.2 mL p = 0.002). Within 6 days, LBW infants achieved a similar GFR to NBW infants, despite 25% smaller kidney volumes. Thus, the single-nephron glomerular filtration rate must be increased in LBW infants. Prior to this study, it was unclear when hyperfiltration begins, but our results demonstrate that hyperfiltration begins in early life.
Publisher: The Endocrine Society
Date: 04-10-2008
DOI: 10.1210/EN.2007-0662
Abstract: The myometrium undergoes substantial remodeling at the time of labor including rearrangement of the cellular contractile machinery. The regulation of this process in human myometrium at the time of labor is poorly defined, but evidence in other muscle types suggests modulation by small heat shock proteins (sHSP). The aim of this study was to investigate whether similar changes in sHSP occur in the myometrium at labor. Using a quantitative proteomic approach (two-dimensional difference gel electrophoresis), we found a 69% decrease in the sHSP αB-crystallin in the myometrium at labor plus multiple isoforms of HSP27. Immunoblotting using phosphospecific HSP27 antibodies (HSP27-serine15, -78, and -82) detected marked changes in HSP27 phosphorylation at labor. Although total HSP27 levels were unchanged, HSP27-Ser15 was 3-fold higher at labor. Coimmunoprecipitation studies showed that HSP27 coprecipitates with αB-crystallin and also smooth muscle α-actin. Coimmunofluorescence studies demonstrated a relocation of HSP27 from the perinuclear region to the actin cytoskeleton at labor. The functional significance of these changes was demonstrated in vitro where myometrial strips stimulated to contract with oxytocin exhibited increased HSP27-Ser15 phosphorylation. Our findings provide data consistent with a novel pathway regulating human myometrial contraction at labor and identify HSP27 and αB-crystallin as potential targets for future tocolytic design.
Publisher: The Endocrine Society
Date: 04-2002
DOI: 10.1210/JC.87.4.1660
Publisher: Public Library of Science (PLoS)
Date: 17-11-2022
DOI: 10.1371/JOURNAL.PONE.0277885
Abstract: Caesarean section has a significant role in reducing maternal and neonatal mortality. A linked analysis of population and health facility data is valuable to map and identify caesarean section use and associated factors. This study aimed to identify geographic variation and associated factors of caesarean delivery in Ethiopia. Linked data analysis of the 2016 Ethiopia Demographic and Health Survey (EDHS) and the 2014 Ethiopian Service Provision Assessment Plus (ESPA+) survey was performed. Spatial analysis was conducted to identify geographic variations and factors associated with caesarean delivery. Hierarchical Bayesian analysis was also performed to identify factors associated with caesarean delivery using the SAS MCMC procedure. Women’s age and education, household wealth, parity, antenatal care (ANC) visits, and distance to caesarean section facility were associated with caesarean delivery use. Women who had ≥4 ANC visits were 4.67 (95% Credible Interval (CrI): 2.17, 9.43) times more likely to have caesarean delivery compared to those who had no ANC visits. Women who had education and were from rich households were also 2.80 (95% CrI: 1.83, 4.19) and 1.80 (95% CrI: 1.08, 2.84) times more likely to have caesarean deliveries relative to women who had no education and were from poor households, respectively. A one-kilometer increase in distance to a caesarean section facility was associated with an 88% reduction in the odds of caesarean delivery (Adjusted Odds Ratio (AOR) = 0.12, 95% CrI: 0.01, 0.78). Hotspots of high caesarean section rates were observed in Addis Ababa, Dire Dawa, and the Harari region. In addition, women’s age at first childbirth and ≥4 ANC visits showed significant spatially varying relations between caesarean delivery use across Ethiopia. Caesarean section is a lifesaving procedure, and it is essential to narrow disparities to reduce maternal and neonatal mortality and avoid unnecessary procedures.
Publisher: Elsevier BV
Date: 03-1990
DOI: 10.1016/0304-3940(90)90871-6
Abstract: It is not certain which protein kinase (A, C or both) is involved in the acute phase of beta-endorphin (beta-EP) release stimulated in the corticotrope by vasopressin (VP) and corticotropin-releasing factor (CRF). We have employed an isolated ovine anterior pituitary cell superfusion system to determine the dynamic effects of forskolin, a protein kinase A (PKA) stimulator, and phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator. Both secretagogues stimulated beta-EP release within 5 min and therefore both PKA and PKC are potential mediators of the acute phase of hormonal stimulation of the corticotrope. Pretreatment with PMA specifically desensitized the pituitary cell columns to subsequent PMA exposure while not significantly altering sensitivity to forskolin or 50 mM KCl.
Publisher: American Astronomical Society
Date: 02-09-2015
Publisher: Georg Thieme Verlag KG
Date: 21-09-2013
Abstract: We performed a study to assess whether the development of the retinal microvasculature reflects nephron growth and therefore nephron number. In our study, we determined the association between kidney volume (nephron number) and the retinal microvasculature of term low-birth-weight (LBW) and normal-birth-weight (NBW) infants (11 LBW and 27 NBW). LBW infants had significantly larger retinal arteriolar and venular diameters (104.2 ± 21.4 versus 87.0 ± 12.7 μm p = 0.004 146.8 ± 19.5 versus 128.0 ± 19.5 μm p = 0.01, respectively) compared with NBW infants. LBW infants also had smaller mean renal volumes (9.3 ± 2.3 versus 12.2 ± 3.1 ml p = 0.008). There were negative correlations between retinal arteriolar and venular diameters and renal volumes (r = -0.34, p < 0.05 r = -0.37, p < 0.05, respectively). The larger the kidney (and, by implication, the greater the nephron number), the smaller are the diameters of retinal arterioles and venules. Thus, the degree of dilation of the retinal microvasculature provides an indirect index of renal growth.
Publisher: The Endocrine Society
Date: 04-1996
DOI: 10.1210/JC.81.4.1406
Publisher: The Endocrine Society
Date: 11-09-2018
Publisher: The Endocrine Society
Date: 10-1995
DOI: 10.1210/JCEM.80.10.7559870
Abstract: This study has used an in vitro perfusion method to investigate the mechanism by which CRH causes vasodilatation in the human fetal-placental circulation. In normal term placentas, vasodilatory responses to human CRH (24-7000 pmol/L) were examined during submaximal vasoconstriction (100-120 mm Hg) of the fetal-placental vasculature induced by prostaglandin F2 alpha (0.7-2 mumol/L), KCl (50-100 mmol/L), or the thromboxane A2 mimetic, U46619 (0.05-0.5 mumol/L). Infusion of CRH caused a concentration-dependent vasodilatation that was similar in the presence of each constrictor agent (P > 0.05). The CRH antagonist, alpha-helical CRH-(9-41) (200 pmol/L), and a polyclonal CRH antiserum significantly inhibited CRH-induced vasodilatation during constriction with prostaglandin F2 alpha (P < 0.05). Vasodilatory responses to CRH were attenuated by the nitric oxide synthase inhibitor, N omega-nitro-L-arginine (100 mumol/L P < 0.05), and the guanylate cyclase inhibitor, LY 83583 (1 mumol/L P 0.05). In placentas of women with increased fetal vascular resistance, as demonstrated by Doppler ultrasound waveforms in vivo, CRH-induced vasodilatation was significantly reduced (P < 0.05). These results indicate that in the human fetal-placental circulation, CRH causes a vasodilatory response via a nitric oxide-/cGMP-dependent pathway. CRH may play a role in the control of vascular resistance to blood flow in the normal human placenta, and there may be a deficiency in the CRH signaling pathway of placentas with increased fetal vascular resistance.
Publisher: Wiley
Date: 28-02-2020
DOI: 10.1002/BRB3.1579
Publisher: Elsevier BV
Date: 03-1987
DOI: 10.1016/0889-1591(87)90010-9
Abstract: Experiments were undertaken in rats to investigate the effects of in vivo infusion of beta-endorphin (BEP) on subsequent Con A-induced proliferation and interleukin 2 (IL-2) production by spleen cells in vitro. BEP administration induced a dose-dependent enhancement of the proliferative response to Con A. Infusion of the opiate antagonist naloxone (NAL) inhibited the Con A response and infusion of NAL prior to BEP resulted in even further inhibition. None of these treatments resulted in detectable alterations in IL-2 production after 48 h in culture. To demonstrate a direct interaction between BEP and lymphocytes, spleen cells were incubated in vitro with varying concentrations of BEP and/or NAL. Enhanced Con A-induced proliferation was observed following incubation with BEP in the range 10(-12) to 10(-9) M (levels comparable to the effective in vivo doses) and this effect was abrogated by NAL pretreatment (10(-6) M). These data indicate a role for BEP in enhancing lymphocyte reactivity which is to some extent dependent on opiate receptors on the cell surface. This report extends the evidence obtained from in vitro experiments implicating endogenous opioids in modulation of host immunity by demonstrating that these effects can be obtained in vivo.
Publisher: Elsevier BV
Date: 09-1986
DOI: 10.1016/0165-0327(86)90026-1
Abstract: The hypothesis that post-partum psychoses are predominantly mixed affective disorders was tested by administering the dexamethasone suppression test (DST) to seven puerperal psychotics, six puerperal depressives and comparison groups of non-puerperal psychotic and depressed women. The hypothesis received support from the finding that two-third of the puerperal patients had positive DSTs versus one-third of similar non-puerperal patients. An 80% rate of positive DSTs in 19 normal women 5 days post-partum, however, suggested this was an invalid interpretation of this finding, particularly as the majority of these tests returned to normal when repeated several weeks later.
Publisher: The Endocrine Society
Date: 04-1993
DOI: 10.1210/JCEM.76.4.8473382
Abstract: During human pregnancy, plasma CRH immunoreactivity (CRH-IR) rises progressively, peaking during labor and falling after delivery. Among animal species, only higher primates have elevated CRH-IR during pregnancy. This study examines whether changes in plasma CRH-IR in the baboon (Papio hamadryas) are similar to those in the human. CRH-IR was determined by RIA in 16 baboons at different stages of gestation (44 s les) and in 3 males. Assays were performed on Vycor extracts of plasma and CRH-IR diluted in parallel to synthetic human (h) CRH-41 standard. Reverse phase high pressure liquid chromatography and size-exclusion chromatography with Sephadex G-50 showed that baboon CRH-IR eluted in a position similar to that of hCRH-41. Regression analysis revealed a cubic association between plasma CRH-IR and gestational age, with peak concentrations occurring at 60 days gestation (term = 182 days). Although greatly elevated concentrations persisted throughout pregnancy, concentrations in the first half (1-91 days) were significantly higher (mean +/- SEM, 1.9 +/- 0.3 nM/L n = 27) than in the second half (92-182 days 1.0 +/- 0.2 nM/L n = 11 P < 0.003 by t test). CRH-IR fell to low levels by day 1 postpartum. The concentration of total cortisol in nonpregnant animals was 1370.9 +/- 134.9 nM/L (n = 5), which was similar to pregnancy levels (1346.3 +/- 356.1 nM/L n = 28) there was no gestational age-related pattern evident. Plasma corticosteroid-binding globulin was estimated by RIA, and plasma free cortisol was calculated to be 73 +/- 14 nM/L in pregnant animals and showed no gestational age-related changes. The mean progesterone concentration in the pregnant baboon was 12.5 +/- 2.2 nM/L (7-169 days n = 27). There was no significant change in progesterone levels during the period of gestation studied however, they were higher than nonpregnant levels. Baboon and human plasma (0.1 mL each) were incubated with [125I]Tyr-hCRH in Tris-HCl buffer (pH 7.5) and chromatographed with Sephadex G-75, using the same buffer. The radioactivity of fractions was determined, and no CRH-binding protein was identified in baboon plasma. This study indicates that gestational changes in CRH-IR in the baboon are different from those observed in humans. There is a dissociation between maternal plasma CRH and cortisol. The apparent lack of bioactivity of baboon plasma CRH is not due to a circulating binding protein, which is absent in this species.
Publisher: Elsevier BV
Date: 1990
DOI: 10.1016/0022-3999(90)90008-R
Abstract: The relationships between mood change, obstetric experience and alterations in plasma cortisol, beta-endorphin (beta-EP) and corticotrophin-releasing hormone (CRH) were examined in a prospective study of 97 primiparous Australian women. Psychological measures were administered between the 28th week of pregnancy and the 3rd postnatal month, including the Profile of Mood States (POMS) and the Montgomery Asberg Depressive Rating Scale (MADRS). Blood s les were collected for cortisol, beta-EP and CRH assay on most of these occasions and during labour. Factor analysis was used to identify key subsets of psychological variables for use in the subsequent analyses. 'Mood disturbance' and 'tiredness' factors peaked at 38 weeks' gestation, while 'difficulty falling asleep' was greatest around the time of birth. Cortisol, beta-EP and CRH concentrations rose significantly as pregnancy advanced and peaked at birth plasma CRH correlated with plasma cortisol (r = 0.54) and beta-EP (r = 0.32). Women with the highest 'mood disturbance' and MADRS depression scores at 28 weeks' gestation received significantly more pain relief during labour. Those women whose mood deteriorated from 38 weeks' gestation to postnatal day 2 had larger falls in plasma beta-EP after delivery (p less than 0.01) than those women whose mood improved or remained constant. Women in this mood-deteriorated subgroup also had significantly higher MADRS depression scores at 3 months (p less than 0.01). Mild antenatal depression (MADRS greater than 13) occurred in 5.2% of women and mild postnatal depression in 4.7%. Overall, these data suggest a role for circulating CRH in the regulation of maternal cortisol secretion and significant relationships between maternal postnatal mood states and beta-EP and between antenatal mood states and obstetric events.
Publisher: Elsevier BV
Date: 03-1991
DOI: 10.1016/S0950-351X(05)80102-8
Abstract: Plasma cortisol, adrenocorticotrophic hormone (ACTH), beta-endorphin and corticotrophin releasing hormone or factor (CRF) all rise progressively as pregnancy advances, and fall postnatally. The placenta produces large amounts of CRF in the third trimester and this is released into the maternal circulation. Present evidence suggests that it stimulates the maternal pituitary to produce ACTH while desensitizing the maternal pituitary to further stimulation with CRF. Maternal control of ACTH production is retained, allowing a persistent response to stress and a diurnal rhythm, perhaps through the secretion of vasopressin. The placenta also produces pro-opiomelanocortin peptides however, the nature of the fragments produced from the precursor differs from that formed in the anterior pituitary of the mother and the role of these fragments in the control of maternal adrenal function is unclear. These changes in the hypothalamo-pituitary-adrenal axis during pregnancy are associated with loss of the normal suppression of cortisol by dexamethasone and elevated basal levels of cortisol with preservation of a diurnal rhythm, features also found in some patients with endogenous depression. Several studies have suggested a relationship between alterations in maternal concentrations of cortisol and beta-endorphin and the development of postnatal mood disturbances.
Publisher: Oxford University Press (OUP)
Date: 08-1994
Abstract: McLean M, Thompson D, Zhang H-P, Brinsmead M, Smith R. Corticotrophin-releasing hormone and β-endorphin in labour. Eur J Endocrinol 1994 :167–72. ISSN 0804–4643 The objectives of this study were to determine whether the maternal plasma corticotrophin-releasing hormone (CRH) concentration influences the amount of uterine contractility induced by infused oxytocin during induction of labour, and secondly to assess changes in CRH and β-endorphin in response to stress during labour. Serial plasma CRH and β-endorphin measurements were made in 40 women undergoing induction of labour and correlated with uterine contractility, cervical dilatation, length of labour, analgesic usage and fetal distress. The plasma CRH concentration did not change throughout labour. In subjects receiving infused oxytocin there was a significant positive correlation between plasma CRH and the amount of uterine activity, and a high plasma CRH level was associated with shorter labour. The plasma β-endorphin level rose with progressive cervical dilatation and fell after epidural anaesthesia. The plasma CRH level did not correlate with the plasma β-endorphin level or rise with fetal distress. We conclude that high levels of maternal plasma CRH are associated with an increase in the uterine contractile response to infused oxytocin. The maternal plasma CRH level does not vary in response to maternal or fetal stress, but β-endorphin secretion does rise in response to the stress of labour and is influenced by pain perception. Mark McLean, Endocrine Unit, John Hunter Hospital, Locked Bag 1, Newcastle Mail Centre, Newcastle, NSW 2310, Australia
Publisher: MDPI AG
Date: 25-02-2015
DOI: 10.3390/NU7031464
Publisher: Springer Science and Business Media LLC
Date: 05-05-2011
DOI: 10.1007/S10995-011-0782-0
Abstract: Folate and vitamin B12 are involved in homocysteine metabolism and are critical to the methylation of DNA. We aimed to assess plasma vitamin B12 (pB12), plasma folate (pFol), and red cell folate (rcFol) in women and their infants during pregnancy and after birth. Maternal biomarkers were tested as predictors of infant biomarkers, including plasma homocysteine (pHcy), at age 6 months. Participants (n = 153) were recruited at the John Hunter Hospital, Australia. Maternal fasting blood s les were collected at 20 and 36 weeks gestation, and at 14 and 27 weeks postpartum. Fifty healthy, term infants provided non-fasting s les at age 6 months. Plasma homocysteine data were available for 16 infants at age 6 months. Maternal pB12 concentrations fell by 16% from 20 to 36 weeks gestation, but had recovered by 14 weeks postpartum. Maternal rcFol concentrations fell by 31% from 20 weeks gestation to 27 weeks postpartum. Infants breastfed at 6 months had lower pB12 (median 159 vs. 402 pmol/L, n = 23 vs. 18, P < 0.01) and folate (median folate z-score -0.58 vs. 0.85, n = 23 vs. 17, P < 0.01), and higher pHcy (median 11.9 vs. 7.3 μmol/L, n = 8 vs. 6, P < 0.01), than those on infant formula. Maternal pregnancy pFol, but not pB12, inversely predicted infant pHcy, after adjustment for the infant's current pB12 (P = 0.04). Changes in maternal B12 and folate occur during pregnancy and after birth. Infant homocysteine metabolism may be regulated through maternal folate concentrations during pregnancy and postnatal feeding.
Publisher: Informa UK Limited
Date: 06-02-2011
DOI: 10.3109/10253890.2010.532576
Abstract: During the perinatal period, the developing brain is sensitive to environmental events. Deleterious programing resulting from infection, dietary restriction, or psychological stress has been observed and affects adult immune and endocrine systems as well as behavior. In this study, we determined whether neonatal infection permanently alters immune and glucocorticoid receptor signaling pathways in the adult hippoc us. A Chlamydia muridarum respiratory infection was induced in male and female mice at birth. Mice were allowed to recover and microarray analysis was conducted on RNA from adult hippoc al tissue. In males, neonatal infection induced an up-regulation of genes associated with cellular development, nervous system development and function, such as cyclin-dependent kinase inhibitor 1A. After neonatal infection, adult females exhibited a T-helper 2 immune bias with genes such as major histocompatibility complex, class II, DQ beta 1 up-regulated. Expression of prolactin, vasopressin, hypocretin, corticotrophin-releasing hormone-binding protein, and oxytocin were confirmed by quantitative real-time polymerase chain reaction. This study shows that neonatal infection differentially alters the gene expression profiles of both female and male mice along immune and neuroendocrine pathways.
Publisher: The Endocrine Society
Date: 02-2004
Abstract: We tested the hypothesis that prostaglandin (PGs), PGE2, and PGF2 alpha, stimulate labor and delivery in women, in part, by inducing functional progesterone withdrawal in myometrial cells by increasing the progesterone receptor (PR)-A/PR-B expression ration. PHM1-31 cells (an immortal pregnant human myometrial cell line) were exposed to PGE2, PGF2 alpha, cyclic-8-bromoadenosine monophosphate (8-Br-cAMP) and phorbol 12-myristate 13-acetate (PMA) at various concentrations for 24h. Effects on PR-A and PR-B expression were then assessed by quantitative RT-PCR. PGF2 alpha dose dependently increased PR-A mRNA and the PR-A/PR-B expression ration but did not effect PR-B mRNA. PGE2 dose-dependently increased mRNAs encoding PR-A and PR-B. The PGE2 dose-threshold for PR-A (0.01 nM) was lower than that for PR-B (0.1 nM), which resulted in an initial rise then a gradual fall in PR-A/PR-B expression ration to basal levels in response to PGE2. Activation of the protein kinase (PK)-A signaling pathway with 8-Br-cAMP coordinately increased expression of PR-A and PR-B and therefore did not alter the PR-A/PR-B expression ration. In contrast, activation of the PKC signaling pathway with PMA increased expression of PR-A without affecting PR-B and therefore significantly (P<0.05) increased the PR-A/PR-B expression ration. These data demonstrate differential control of myometrial PR-A and PR-B expression by PGE2 and PGF2 alpha and by specific intracellular signaling pathways. We conclude that PGs acting via the PKC pathway facilitate functional progesterone withdrawal by increasing the myometrial PR-A/PR-B expression ratio.
Publisher: Elsevier BV
Date: 03-1989
Publisher: Springer Science and Business Media LLC
Date: 2008
Abstract: At term, amniotic fluid contents may mediate the onset of labor through the activation of amniotic fluid macrophages and their migration into the myometrium. To test this concept, the authors examine the histological changes that occur in myometrial biopsies at term prior to (n = 53) and during (n = 15) labor. Biopsies were stained with an antimacrophage antibody, anti-CD34 (endothelial cells), and anti-caspase 3 (apoptotic cells). The s les showed a variable inflammatory infiltrate of neutrophils and macrophages, with a greater infiltrate in the s les obtained during labor (P < .001, Fisher exact test). Prior to labor, there were prominent changes in the myometrial fibers that reflected shearing, shrinkage, edema, and particularly apoptosis endothelial cells of thin-walled vessels prominent in the biopsies displayed marked nuclear biotinylation, and the vascular lumen contained fibrin and platelet thrombi, microparticles, desquamated endothelial cells, amniotic squamous cells, and mucoid material. These changes were also present in s les obtained during labor. In an additional 10 patients in labor with male fetuses, myometrial s les were examined for the presence of macrophages carrying a Y chromosome indicative of a fetal origin, but none were observed. These findings suggest that endothelial cell damage and amniotic fluid embolism are very common at term prior to clinical labor and provide a mechanism by which surfactant protein A and phospholipids present in the amniotic fluid may access myometrial cells and provoke the inflammatory response that occurs during parturition. The authors' studies give no support to the suggestion that fetal macrophages might invade the human myometrium at term.
Publisher: Oxford University Press (OUP)
Date: 12-02-2022
Abstract: Changes in cell phenotype are thought to occur through the expression of groups of co-regulated genes within topologically associated domains (TADs). In this paper, we allocate genes expressed within the myometrium of the human uterus during the onset of term labour into TADs. Transformation of the myometrial cells of the uterus into a contractile phenotype during term human labour is the result of a complex interaction of different epigenomic and genomic layers. Recent work suggests that the transcription factor (TF) RELA lies at the top of this regulatory network. Using deep RNA sequencing (RNAseq) analysis of myometrial s les (n = 16) obtained at term from women undergoing caesarean section prior to or after the onset of labour, we have identified evidence for how other gene expression regulatory elements interact with TFs in the labour phenotype transition. Gene set enrichment analysis of our RNAseq data identified three modules of enriched genes (M1, M2 and M3), which in gene ontology studies are linked to matrix degradation, smooth muscle and immune gene signatures, respectively. These genes were predominantly located within chromosomal TADs suggesting co-regulation of expression. Our transcriptomic analysis also identified significant differences in the expression of long non-coding RNAs (lncRNA), microRNAs (miRNA) and TFs that were predicted to target genes within the TADs. Additionally, network analysis revealed 15 new lncRNA (MCM3AP-AS1, TUG1, MIR29B2CHG, HCG18, LINC00963, KCNQ1OT1, NEAT1, HELLPAR, SNHG16, NUTM2B-AS1, MALAT1, PSMA3-AS1, GABPB1-AS1, NORAD and NKILA) and 4 miRNA (mir-145, mir-223, mir-let-7a and mir-132) as top gene hubs with three TFs (NFKB1, RELA and ESR1) as master regulators. Together, these factors are likely to be involved in co-regulatory networks driving a myometrial transformation to generate an estrogen-sensitive phenotype. We conclude that lncRNA and miRNA targeting the estrogen receptor 1 and nuclear factor kappa B pathways play a key role in the initiation of human labour. For the first time, we perform an integrative analysis to present a multi-level genomic signature made of mRNA, non-coding RNA and TFs in the myometrium for spontaneous term labour.
Publisher: Wiley
Date: 08-1985
DOI: 10.1111/J.1479-828X.1985.TB00642.X
Abstract: Nineteen women were studied before, during and after labour by assessment of their mood using a variety of psychological tests and by measurement of their plasma concentrations of beta-endorphin and cortisol. Beta-endorphin and cortisol concentrations rose markedly during labour and were influenced by the type of analgesia used. A deterioration in cognitive performance between days 2 and 4 postpartum correlated positively with the fall in beta-endorphin concentrations from those in labour to those on the fourth day postpartum. The women were more anxious and depressed at 38 weeks' gestation than on days 1-4 postpartum and the elevation of mood on day 2 postpartum correlated with a measure of depression 8 weeks later. It is postulated that the phenomenon of postpartum blues is a reaction to the euphoria of delivery which in turn is a response to endorphin release during labour. Whilst these changes may have a role in promoting maternal-infant attachment it is at the expense of maternal depression some weeks later.
Publisher: Wiley
Date: 17-10-2012
DOI: 10.1002/DEV.20615
Abstract: The current study investigated the effects of neonatal infection with Chlamydia muridarum bacteria on glucocorticoid (GR) and mineralocorticoid (MR) receptors in the adult mouse hippoc us. In male adults infected at birth, circulating corticosterone was significantly increased when compared to same sex controls while neonatal infection resulted in female adults with significantly increased GR mRNA compared to same sex controls. When comparing males and females after neonatal infection, males had significantly less GR protein than females. Interestingly, after control treatment, males had significantly more GR mRNA, MR mRNA, and GR protein with significantly lower corticosterone than females. Neonatal respiratory infection significantly impacts adult hippoc al GR and MR, and circulating corticosterone in a sex-specific manner potentially altering stress responsivity.
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.PLACENTA.2016.01.003
Abstract: Workshops are an important part of the IFPA annual meeting, as they allow for discussion of specialized topics. At the IFPA meeting 2015 there were twelve themed workshops, three of which are summarized in this report. These workshops were related to various aspects of placental biology but collectively covered areas of pregnancy pathologies and placental metabolism: 1) nanomedicine applications and exosome biology 2) xenobiotics and endocrine disruptors and pregnancy 3) lipid mediators and placental function.
Publisher: Bioscientifica
Date: 08-1988
Abstract: The placenta has been shown to contain ACTH and β-endorphin but the roles of these peptides are unknown. To investigate whether they are released into the maternal circulation from the placenta in response to physiological stimuli the effects of hypoglycaemic stress were investigated. Plasma s les were collected from the femoral artery (FA) and uterovarian (UV) vein of nine pregnant sheep before and during hypoglycaemia induced by intravenous insulin (100U). Plasma concentrations of ovine β-endorphin (oβ-EP) were measured by radioimmunoassay. Concentrations of oβ-EP rose in both vessels by 60 min after insulin. The peak concentrations of oβ-EP (pmol/l) were 122 ± 29 (mean ± SEM, n=8) in the UV and 96±24 (n=9) fmol/ml in the FA 60 min after insulin injection. There was no difference between the concentrations of oβ-EP in the vessels before insulin injection but at 60 and 120 min after insulin the concentrations of oβ-EP were significantly higher in the UV than FA (P .02, analysis of variance). This indicates that the pregnant uterus or placenta can respond to hypoglycaemia by secreting β-EP into the maternal circulation. It is therefore possible that placental pro-opiomelanocortin (POMC) peptides may have a role in maternal endocrinology and metabolism.
Publisher: Wiley
Date: 13-09-2012
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.AJOG.2022.02.029
Abstract: Evidence supports a role for placental aging in the etiology of the majority of fetal deaths. This knowledge may reduce maternal feelings of guilt following fetal death that frequently exacerbates the distress caused by grief. The accompanying video may be a useful resource for women who have experienced a fetal death.
Publisher: Springer Science and Business Media LLC
Date: 21-04-2016
Publisher: Wiley
Date: 27-02-2017
DOI: 10.1111/AJI.12653
Abstract: Oxidative stress (OS), an imbalance between free radical generation and antioxidant defence, is recognized as a key factor in the pathogenesis of adverse pregnancy outcomes. Although OS is a common future of normal pregnancy, persistent, overwhelming OS leads to consumption and decline of antioxidants, affecting placental antioxidant capacity and reducing systems. The accumulation of OS causes damage to lipids, proteins and DNA in the placental tissue that induces a form of accelerated ageing. Premature ageing of the placenta is associated with placental insufficiency that prevents the organ meeting the needs of the foetus, and as a consequence, the viability of the foetus is compromised. This review summarizes the literature regarding the role of OS and premature placental ageing in the pathophysiology of pregnancy complications.
Publisher: Oxford University Press (OUP)
Date: 15-02-2016
DOI: 10.1093/MNRAS/STW347
Publisher: Springer Science and Business Media LLC
Date: 15-11-2019
DOI: 10.1186/S12978-019-0829-Z
Abstract: Skilled delivery care utilization in Ethiopia is still very low compared with the goal set by the global community for countries with the highest maternal mortality. As a result, the country is overburdened with high maternal morbidity and mortality. We aimed to explore the predisposing, enabling, and need factors associated with skilled delivery care utilization among reproductive-aged women in Kersa district, eastern Ethiopia. A community-based cross-sectional study was conducted with a total of 1294 women. The participants were selected using systematic s ling techniques. An interviewer-administered structured questionnaire aided by an electronic survey tool was used to collect data. Univariate analyses were conducted to describe the study s le. Bivariate and multivariate logistic regression analyses were carried out to elicit the association of predisposing, enabling, and need factors associated with skilled delivery care utilization. Separate multivariate models were fitted for primiparous and multiparous women categories. Odds ratios with 95% confidence intervals were used to assess statistical significance. More than a quarter (30.8%) of the women surveyed used skilled delivery care for their most recent birth. Significant predisposing factors were as follows: presence of educated family member receiving education on maternal health previous use of skilled delivery care and best friend’s use of maternal care. Place of residence was the enabling factor that predicted skilled delivery care use. Antenatal care attendance and pregnancy intention were significant need factors associated with skilled delivery care utilization. The findings of the study highlight the need for a concerted effort to establish community-based peer education programs improve access to family planning services (to reduce unintended pregnancies) increase antenatal care uptake and facilitate access to skilled delivery care in rural areas.
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.AJOG.2016.08.027
Abstract: The ability to provide safe and effective pharmacotherapy during obstetric complications, such as preterm labor or postpartum hemorrhage, is h ered by the systemic toxicity of therapeutic agents leading to adverse side effects in the mother and fetus. Development of novel strategies to target tocolytic and uterotonic agents specifically to uterine myocytes would improve therapeutic efficacy while minimizing the risk of side effects. Ligand-targeted liposomes have emerged as a reliable and versatile platform for targeted drug delivery to specific cell types, tissues or organs. Our objective was to develop a targeted drug delivery system for the uterus utilizing an immunoliposome platform targeting the oxytocin receptor. We conjugated liposomes to an antibody that recognizes an extracellular domain of the oxytocin receptor. We then examined the ability of oxytocin receptor-targeted liposomes to deliver contraction-blocking (nifedipine, salbutamol and rolipram) or contraction-enhancing (dofetilide) agents to strips of spontaneously contracting myometrial tissue in vitro (human and mouse). We evaluated the ability of oxytocin receptor-targeted liposomes to localize to uterine tissue in vivo, and assessed if targeted liposomes loaded with indomethacin were capable of preventing lipopolysaccharide-induced preterm birth in mice. Oxytocin receptor-targeted liposomes loaded with nifedipine, salbutamol or rolipram consistently abolished human myometrial contractions in vitro, while oxytocin receptor-targeted liposomes loaded with dofetilide increased contraction duration. Nontargeted control liposomes loaded with these agents had no effect. Similar results were observed in mouse uterine strips. Following in vivo administration to pregnant mice, oxytocin receptor-targeted liposomes localized specifically to the uterine horns and mammary tissue. Targeting increased localization to the uterus 7-fold. Localization was not detected in the maternal brain or fetus. Targeted and nontargeted liposomes also localized to the liver. Oxytocin receptor-targeted liposomes loaded with indomethacin were effective in reducing rates of preterm birth in mice, whereas nontargeted liposomes loaded with indomethacin had no effect. Our results demonstrate that oxytocin receptor-targeted liposomes can be used to either inhibit or enhance human uterine contractions in vitro. In vivo, the liposomes localized to the uterine tissue of pregnant mice and were effective in delivering agents for the prevention of inflammation-induced preterm labor. The potential clinical advantage of targeted liposomal drug delivery to the myometrium is reduced dose and reduced toxicity to both mother and fetus.
Publisher: American Astronomical Society
Date: 19-03-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 1996
DOI: 10.1016/0029-7844(95)00338-X
Abstract: To determine whether placental secretion of corticotropin-releasing hormone into the fetal circulation is increased in pregnancies complicated by umbilical-placental vascular insufficiency. Twenty women with abnormal Doppler umbilical artery flow velocity waveforms and six women with uncomplicated term pregnancies and normal umbilical artery flow velocity waveforms had cord blood concentrations of corticotropin-releasing hormone, ACTH, cortisol, and beta-hCG estimated. The mean cord blood corticotropin-releasing hormone concentration was significantly higher in pregnancies with abnormal umbilical artery flow velocity waveforms than in normal pregnancies (108 +/- 27 versus 24 +/- 8 pg/mL, P = .019). Elevated cord blood corticotropin-releasing hormone levels were seen in the abnormal group regardless of the presence or absence of preecl sia or fetal growth restriction. There were no significant differences in cord blood cortisol, ACTH, or beta-hCG concentrations. The concentration of corticotropin-releasing hormone in the fetal circulation is significantly increased in pregnancies complicated by abnormal umbilical artery flow velocity waveforms. This may represent a stress-responsive compensatory mechanism in the human placenta.
Publisher: Public Library of Science (PLoS)
Date: 22-07-2005
Publisher: Wiley
Date: 13-09-2012
DOI: 10.1111/J.1440-1754.2012.02557.X
Abstract: The frequency of premature births is increasing world-wide. This factor, combined with improved survival and revised screening criteria, is resulting in an increased workload in screening for retinopathy of prematurity. Digital retinal imaging is emerging as an important alternative tool for diagnosing retinopathy of prematurity, and its use has even been extended to developing countries. Neonatal nurses and technicians can be trained to use digital imaging devices effectively. This is important in areas that do not have ready access to paediatric ophthalmologists. The ability to transfer images electronically makes it a valuable tool in telemedicine, while the ability to store and retrieve images is also advantageous from a medico-legal perspective. Image analysis software can further improve the accuracy of diagnosis. The main limitation of this technology is its high capital cost.
Publisher: The Endocrine Society
Date: 12-1998
Publisher: Elsevier BV
Date: 05-2020
DOI: 10.1016/J.WOMBI.2019.04.006
Abstract: In Ethiopia, maternal health service utilization is still unacceptably low. The societal and cultural factors that constrain women from attending these services have not yet been sufficiently explored. Using qualitative methods, we aimed to explore the factors that delay maternal health service utilization in eastern Ethiopia. A total of 13 audio-recorded focus group discussions were conducted comprising 88 participants. We conducted separate group discussions with reproductive aged women, mothers-in-law, traditional birth attendants, husbands, and Health Extension Workers to capture their knowledge, practices, feelings, thoughts and attitudes towards maternal health service utilization. The recorded sessions were transcribed into the local language and then translated into English for analysis. The study identified a number of factors that may delay maternal health service utilization. Factors were grouped using the Three Delays model as a framework. Low level of awareness regarding need, poor involvement of husband, perceived absence of health problems, social power, community misperceptions and cultural restrictions, negative attitudes towards male midwives, acceptance of traditional birth attendants and poor social networking were Delay One factors. Lack of physical accessibility and high transportation costs were categorised as Delay Two factors for skilled birth care attendance. Perceived or experienced poor quality of care were categorised as Delay Three factors for both skilled birth and postnatal care utilization. Despite the ongoing government measures to improve maternal health service utilization in Ethiopia, numerous factors continue to contribute to delays in service use, which in turn contribute to high maternal mortality.
Publisher: Wiley
Date: 23-12-2019
DOI: 10.1111/DME.14207
Abstract: To examine the challenges healthcare teams face when treating people with type 1 diabetes and disordered eating and the strategies these teams have developed to facilitate effective treatment. Four semi-structured focus groups were conducted including two tertiary diabetes specialist teams and three tertiary eating disorders specialist teams between July and December 2018. Thematic analysis of the transcripts followed a six-phase process. Twenty-nine experienced healthcare professionals (16 diabetes and 13 eating disorder specialists, 16±12 years' professional experience) were interviewed. The challenges identified in treating people with type 1 diabetes and disordered eating included subthemes the 'challenges specific to the healthcare professional' (feeling not competent enough and perceived emotional burden), 'challenges pertaining to patient factors' (e.g. difficulties with engaging in therapy) and 'challenges created by the healthcare system' (time pressure and staff shortage). Healthcare professionals expressed the need for a consensus on diagnosis and the definition of disordered eating in type 1 diabetes, as well as the need for training and educational resources specific to type 1 diabetes and disordered eating. Healthcare professionals gave practical ex les of strategies of communication for better patient engagement and felt that multidisciplinary working in joint clinics with the other specialty were facilitators for recovery from disordered eating. Healthcare professionals require multidisciplinary team support when treating people with type 1 diabetes and to improve their own competencies. The development of effective screening and assessment tools, educational resources and training for healthcare professionals, and developing multidisciplinary treatment pathways will be key to improving outcomes for their service users with type 1 diabetes and disordered eating.
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.PLACENTA.2013.01.015
Abstract: Unexplained antepartum stillbirth is a major obstetric health problem. Data demonstrate a rapid rise in risk per 1000 continuing pregnancies as gestation advances beyond 40 weeks. We review the evidence that such stillbirths are a consequence of aging related changes in the late gestation placenta. We suggest that the relatively small number of continuing pregnancies after 40 completed weeks means that negative effects of genes that produce aging affect so few pregnancies that polymorphisms in genes that produce these effects are retained in the population. Aging related changes likely represent a consequence of the damaging effects of oxidative stress, increased by cigarette smoking counteracted by the mitigating effects of oxidative defence pathways. The aging related changes are likely downstream from nutrient sensing units such as mTOR and include effects on production of telomerase and consequent shortening of telomere length. The late gestation changes occur in the context of increasing fetal growth and nutrient supply demands that can produce the rapid development of a mismatch between placental supply and fetal need resulting in fetal demise. Premature aging may also play an important role in antepartum stillbirth occurring earlier in pregnancy, especially in the context of growth restriction.
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/861302
Abstract: Corticotropin releasing hormone (CRH) production by the human placenta increases exponentially as pregnancy advances, and the rate of increase predicts gestational length. CRH gene expression is regulated by cAMP in trophoblasts through a cyclic AMP-response element (CRE), which changes its transcription factor binding properties upon methylation. Here we determined whether methylation of the CRH proximal promoter controls basal and cAMP-stimulated CRH expression in BeWo cells, a well-characterized trophoblastic cell line. We treated the cells with 8-Br-cAMP and the DNA methyltransferase inhibitor 5-aza-2′ deoxycytidine (5-AZA-dC) and determined the effects on CRH mRNA level and promoter methylation. Clonal bisulfite sequencing showed partial and allele independent methylation of CpGs in the CRH promoter. CRH mRNA expression and the methylation of a subset of CpGs (including CpG2 in the CRE) increased spontaneously during culture. 8-Br-cAMP stimulated CRH expression without affecting the increase in methylation. 5-AZA-dC decreased methylation and augmented 8-Br-cAMP-stimulated CRH expression, but it blocked the spontaneous increase of CRH mRNA level. We conclude that the CRH promoter is a dynamically and intermediately methylated genomic region in BeWo cells. Promoter methylation did not inhibit CRH gene expression under the conditions employed rather it determined the contribution of alternative cAMP-independent pathways and cAMP-independent mechanisms to CRH expression control.
Publisher: Public Library of Science (PLoS)
Date: 11-04-2019
Publisher: S. KARGER AG
Date: 2014
DOI: 10.1159/000356110
Publisher: MDPI AG
Date: 24-04-2015
DOI: 10.3390/NU7053078
Publisher: Canadian Science Publishing
Date: 02-2006
DOI: 10.1139/O05-139
Abstract: We describe a unique family of human proteins that are capable of binding to the cAMP regulatory element (CRE) and that are homologous to RNA splicing proteins. A human cDNA was isolated that encodes a protein with a distinctive combination of modular domain structures: 2 leucine-zipper-like domains, a DNA-binding zinc-finger-like domain, an RNA-binding zinc-finger-like domain, and 2 coiled-coil protein–protein interaction domains. It also has a serine–arginine - rich domain, commonly found in proteins involved in RNA splicing. The protein was discovered using the CRE as bait in a yeast 1-hybrid assay. It was then shown to bind specifically to the CRE in vitro using gel shift assays. We have named the protein CRE-associated protein (CREAP). We show that it is widely expressed in human tissues but is highly expressed in several fetal tissues and in several regions of the adult brain. CREAP is closely related to 2 human proteins of unknown function. CREAP shows significant homology with a small nuclear ribonucleoprotein of yeast, Luc7p, involved in 5′ splice site recognition. The 3 human CREAP proteins form a unique family with the potential to act as transcription factors that link to RNA processing.Key words: multifunctional protein, zinc finger, bZIP, transcription factor, splicing factor, protein family, CRH, CRE.
Publisher: Wiley
Date: 04-1990
DOI: 10.1111/J.1365-2826.1990.TB00848.X
Abstract: Abstract We have employed an in vitro system to study the time-course of beta-endorphin (beta-EP) immunoreactivity release from anterior pituitary cells stimulated with corticotropin-releasing factor (CRF) and whether exposure to CRF desensitizes the cells to subsequent stimulation. Ovine anterior pituitaries were enzymatically disrupted into single cells, mixed with Siegel P2 and superfused in mini-columns with carbogen-gassed medium at 37 degrees C. Superfusate fractions were collected at 5-min intervals and beta-EP immunoreactivity in the eluate was measured by radioimmunoassay. Peaks of beta-EP release that rose significantly above baseline noise were detected using the PULSAR algorithm. Unstimulated cell columns did not display any spontaneous peaks of beta-EP discharge detectable by PULSAR whereas peaks were identified in the output of columns exposed to 1 nM CRF for 100 min. beta-EP release increased after 10 min of stimulation and maximum stimulated output was achieved after 20 min of continuous CRF exposure. Between 20 and 60 min of CRF stimulation the rate of beta-EP release declined progressively but stabilized in the last 40 min of the exposure at a level significantly above controls for baseline secretion. Peak duration did not depend on the inclusion of calcium in the superfusion medium while peak litude and area were significantly reduced when cells were denied extracellular calcium. Following a 100-min exposure to 1 nM CRF, pituitary cell columns were given a 30-min rest period then restimulated with either 1 nM CRF or 50 mM KCI for 20 min. The columns given prior exposure to CRF did not mount a response (detectable by PULSAR) to a subsequent dose of 1 nM CRF whereas PULSAR detected a clear response in all members of a control group that had not received prior CRF challenge. Both CRF exposed and control columns responded to 50 mM KCI although the response was significantly attenuated in the cells that had received prior CRF treatment. These results indicate that unstimulated superfused isolated ovine anterior pituitary cells do not possess an inherent rhythmicity of beta-EP release that can be detected by the PULSAR algorithm while treatment of the cells with CRF results in detectable discharge. The rapid response of beta-EP discharge to CRF treatment suggests the presence of intracellular beta-EP stores available for rapid mobilization. Continuous exposure to 1 nM CRF can tonically lify corticotrope output for the duration of its presence in the environment of the corticotrope, but the maximum rate of release cannot be maintained. An inrush of extracellular calcium is not essential for the corticotrope to mount a detectable response to continuous CRF exposure but the release of a maximum amount of beta-EP relies on calcium entry. Long-term treatment with CRF prevents the corticotrope releasing a detectable peak of beta-EP on subsequent CRF stimulation and therefore CRF exposure leaves a lasting impression on the physiological machinery of the corticotrope. The attenuation of responsiveness to 50 mM KCI after long-term CRF treatment indicates that depletion of beta-EP stores may play a part in corticotrope desensitization although a reduction in CRF receptor number and an alteration in the intracellular mechanisms controlling beta-EP release may also be a factor.
Publisher: Public Library of Science (PLoS)
Date: 06-12-2018
Publisher: The Endocrine Society
Date: 03-2000
DOI: 10.1210/JC.85.3.1239
Publisher: Elsevier BV
Date: 10-1987
DOI: 10.1016/0024-3205(87)90603-5
Abstract: We recently observed that the characteristic insensitivity of the pituitary-adrenal system in women to feedback inhibition during pregnancy persists for at least four days postnatally. We therefore examined women during the first five weeks after delivery to assess when the sensitivity of plasma cortisol to glucocorticoid inhibition returns to normal. Dexamethasone (DEXA, 1 mg) was ingested at 11 pm by normal healthy women, once between the 3rd and 27th postnatal days, and again on day 35. Blood plasma was collected at 4 pm on the following day for cortisol assay. Plasma cortisol levels (nmol/L, mean +/- sem [n]) after DEXA in the first two weeks (216 +/- 28, [47]) were higher (p less than 0.001) than in nonmedicated nonpregnant women (47.4 +/- 8.9 [12]) and were normal by the 35th day after delivery (41.7 +/- 4.8 [74]). A negative association was found between post-DEXA cortisol and time after delivery in the first 4 post-partum weeks (r = -0.46, p less than 0.001). The study confirms that insensitivity of plasma cortisol to feedback inhibition persists beyond normal pregnancy in a significant proportion of healthy women for two to three weeks, and is absent by the 5th postnatal week.
Publisher: The Endocrine Society
Date: 22-03-2011
DOI: 10.1210/EN.2010-0979
Abstract: Estrogens are key mediators of increased uterine contractility at labor. We sought to determine whether membrane-associated estrogen receptors, such as the recently described seven-transmembrane receptor G protein-coupled receptor 30 (GPR30), mediated some of this effect. Using human myometrium obtained at term cesarean section before or after the onset of labor, we demonstrated the presence of GPR30 mRNA and protein using quantitative RT-PCR and Western blotting. GPR30 receptor was localized to the cell membrane and often colocalized with calveolin-1. Using the specific estrogen membrane receptor agonist G-1 and myometrial explants, we showed that membrane receptor activation led to phosphorylation of MAPK and the actin-modifying small heat shock protein 27. Using myometrial strips incubated with G-1 or vehicle we demonstrated that estrogen membrane receptor activation increased the myometrial contractile response to oxytocin. These data suggest that activation of the plasma membrane estrogen receptor GPR30 likely participates in the physiology of the human myometrium during pregnancy and identifies it as a potential target to modify uterine activity.
Publisher: Elsevier
Date: 2010
Publisher: The Endocrine Society
Date: 07-1998
Abstract: In sheep, corticotropin-releasing hormone (CRH) can stimulate the fetal release of ACTH to produce a cortisol surge which leads to the onset of parturition. We tested the hypothesis that fetal CRH is a primary factor in the onset of parturition in sheep by using a Type I CRH receptor antagonist, antalarmin, to block the endogenous action of CRH. Pregnant ewes were cannulated at 130-135 days of gestation. Five catheters were placed into the amniotic sac, fetal femoral artery, fetal tarsal vein, maternal jugular vein and carotid artery. After 5 days' recovery, blood s les from maternal and fetal vessels were collected at the following times: a day before the start of infusion, at [-1, 0, 1, 2, 4, 8 and 24]h, on the first day of infusion, and thereafter daily throughout a 10-day infusion. Animals (n=6 per group) received infusions into a fetal vein of either a vehicle comprising 1:1 mixture of ethanol and polyethoxylated castor oil (Cremophor EL) or antalarmin (50 g/L) in the vehicle at a rate of 0.3 mL/h. The plasma s les were assayed for ACTH and cortisol using commercial RIA kits. Fetuses infused with vehicle delivered at a mean gestational age of 141.8 +/- 0.9 days compared with antalarmin-infused sheep at 148.8 +/- 1.6 days (P = 0.0036, unpaired Student's t-test). Fetal ACTH and cortisol did not change in the antalarmin-infused sheep after 3 days' infusion compared to significant increases in vehicle-infused sheep (P=0.004 and P = 0.016 respectively, ANOVA). These data show that CRH receptor antagonism in the fetus can delay the onset of parturition. It supports the hypothesis that hypothalamic CRH drives fetal production of ACTH and is essential for the onset of parturition triggered by a surge in fetal cortisol.
Publisher: Elsevier BV
Date: 05-2001
DOI: 10.1016/S0196-9781(01)00393-X
Abstract: Corticotrophin-releasing hormone (CRH) is a 41 amino acid neuropeptide that is expressed in the hypothalamus and the human placenta. Placental CRH production has been linked to the determination of gestational length in the human. Although encoded by a single copy gene, CRH expression in the placenta is regulated differently to the hypothalamus. Glucocorticoids stimulate CRH promoter activity in the placenta but inhibit it's activity in the hypothalamus, via mechanisms involving different regions of the CRH promoter. We discuss how various stimuli alter CRH promoter activity and why these responses are unique to the placenta.
Publisher: Springer Science and Business Media LLC
Date: 19-12-2020
DOI: 10.1007/S00360-019-01254-4
Abstract: Nonapeptides and their receptors regulate a erse range of physiological processes. We assessed the contractile responsiveness of uteri from the squamate viviparous-oviparous species pair, Pseudemoia entrecasteauxii and L ropholis guichenoti, as well as the bimodally reproductive species, Saiphos equalis, to arginine vasopressin (AVP). We assessed the resulting uterine contractility as a function of pregnancy status, species and parity mode. We also measured mRNA abundance for the nonapeptide receptor, oxytocin receptor (oxtr), in uteri from P. entrecasteauxii and L. guichenoti and compared expression across pregnancy status and parity mode. We found that pregnant uteri exhibited a significantly greater contractile response to AVP than non-pregnant uteri in all three lizard species studied. Cross-species comparisons revealed that uteri from viviparous P. entrecasteauxii were significantly more responsive to AVP than uteri from oviparous L. guichenoti during both pregnant and non-pregnant states. Conversely, for non-pregnant S. equalis, uteri from viviparous in iduals were significantly less responsive to AVP than uteri from oviparous in iduals, while during pregnancy, there was no difference in AVP contractile responsiveness. There was no difference in expression of oxtr between L. guichenoti and P. entrecasteauxii, or between pregnant and non-pregnant in iduals within each species. We found no significant correlation between oxtr expression and AVP contractile responsiveness. These findings indicate that there are differences in nonapeptide signalling across parity mode and suggest that in these lizards, labour may be triggered either by an increase in plasma nonapeptide concentration, or by an increase in expression of a different nonapeptide receptor from the vasopressin-like receptor family.
Publisher: Elsevier BV
Date: 2018
DOI: 10.2139/SSRN.3304279
Publisher: IMR Press
Date: 2004
DOI: 10.2741/1204
Abstract: Glucocorticoids inhibit corticotrophin releasing hormone (CRH) production in the hypothalamus but stimulate production from the placenta. To identify key elements regulating the CRH gene, mouse pituitary tumor-derived cells (AtT20 cells) were used as a hypothalamic model in an analysis of the CRH promoter. Two cAMP responsive elements were identified: (I) a consensus cAMP response element (CRE) and (II) a previously unrecognized caudal-type homeobox response element (CDXRE). Glucocorticoids inhibit only the component of cAMP-stimulation occurring via the CRE through an action involving a negative glucocorticoid response element (nGRE). We also identified two regions that, in the absence of the nGRE, can be stimulated by glucocorticoids: (I) the CRE and (II) a region between -213 to -99bps. Electrophoretic mobility shift assays identified binding of the transcription factors CREB and Fos at the CRE in AtT20 cells, whereas CREB and cJun were detected in placental cells. In addition, a novel CRE-binding transcription factor has been identified that is expressed in the brain and in placenta. A model is presented whereby CRH gene regulation is mediated via tissue specific expression of transcription factors.
Publisher: Cambridge University Press (CUP)
Date: 21-04-2022
DOI: 10.1017/S2040174422000186
Abstract: Animal and human data demonstrate independent relationships between fetal growth, hypothalamic-pituitary-adrenal axis function (HPA-A) and adult cardiometabolic outcomes. While the association between fetal growth and adult cardiometabolic outcomes is well-established, the role of the HPA-A in these relationships is unclear. This study aims to determine whether HPA-A function mediates or moderates this relationship. Approximately 2900 pregnant women were recruited between 1989-1991 in the Raine Study. Detailed anthropometric data was collected at birth (per cent optimal birthweight [POBW]). The Trier Social Stress Test was administered to the offspring (Generation 2 Gen2) at 18 years HPA-A responses were determined (reactive responders [RR], anticipatory responders [AR] and non-responders [NR]). Cardiometabolic parameters (BMI, systolic BP [sBP] and LDL cholesterol) were measured at 20 years. Regression modelling demonstrated linear associations between POBW and BMI and sBP quadratic associations were observed for LDL cholesterol. For every 10% increase in POBW, there was a 0.54 unit increase in BMI (standard error [SE] 0.15) and a 0.65 unit decrease in sBP (SE 0.34). The interaction between participant’s fetal growth and HPA-A phenotype was strongest for sBP in young adulthood. Interactions for BMI and LDL-C were non-significant. Decomposition of the total effect revealed no causal evidence of mediation or moderation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2015
DOI: 10.11124/JBISRIR-2015-1812
Abstract: What are the effects of weight management interventions that include a diet component on weight-related outcomes in pregnant and postpartum women?The primary objective of this systematic review is to evaluate the effectiveness of weight management interventions which include a diet component and are aimed at limiting gestational weight gain and postpartum weight retention in women.The second objective of this systematic review is to investigate included intervention components with respect to effect on weight-related outcomes. This may include, but is not limited to: length of intervention, use of face-to-face counselling, group or in idual consultations, use of other interventions components including exercise, use of goals and use of support tools like food diaries, coaching, including email or text message support. Around half of all women of reproductive age are either overweight or obese, with women aged 25-34 years having a greater risk of substantial weight gain compared with men of all ages. Excessive gestational weight gain (GWG) and postpartum weight retention (PPWR) may play a significant role in long term obesity. Having one child doubles the five- and 10-year obesity incidence for women, with many women who gain excessive weight during pregnancy remaining obese permanently. Excessive GWG and/or PPWR can also significantly contribute to short- and long-term adverse health outcomes for mother, baby and future pregnancies.Maternal obesity increases the risk of pregnancy related complications such as pre-ecl sia, gestational diabetes mellitus, stillbirth and the rate of caesarean section. Childhood obesity is a further long term complication of maternal obesity for offspring, which may persist in to adulthood. Excess GWG is also a risk factor for PPWR both in the short and long-term. Nehring et al. conducted a meta-analysis with over 65,000 women showing that, compared to women who gained weight within recommendations during pregnancy, women with GWG above Institute of Medicine weight gain recommendations, retained an additional 3.1 kg and 4.7kg after three and greater than or equal to 15 years postpartum, respectively. The health risk associated with PPWR is highlighted in a study of 151,025 Swedish women followed between 1992 and 2001.The study identified the risk of adverse pregnancy outcomes for those who gained three or more units of Body Mass Index (kg/m2) between consecutive pregnancies (an average of two years) was much higher compared with women whose BMI changed from -1.0 and 0.9 units. Long-term chronic disease risk may also be affected by PPWR as weight retention at the end of the first year post-partum has been found to be a predictor of maternal overweight 15 years later.With around 14-20% of women retaining 5kg or more 12 months postpartum, the risk of developing conditions like diabetes, metabolic syndrome and cardiovascular disease may be increased. It becomes evident that interventions which aim to support attainment of healthy weight both in the antenatal and postpartum periods are key health priorities for women during this life stage.Lifestyle factors of overweight, having poor diet quality, and not undertaking enough moderate-to-vigorous physical activity are amongst the top five predictors of mortality in women. Additionally it is noted that, for many women, pregnancy and the postpartum period are associated with a reduction in physical activity. It is known that a combination of poor dietary choices, an increase in sedentary time and reduction in physical activity are all contributors to the development of overweight and obesity. With this in mind, current research has focused on lifestyle interventions to limit GWG and PPWR. Thangaratinam et al. reviewed 44 randomized controlled trials (7278 women) where interventions including diet, physical activity or both were evaluated for their influence on maternal weight during pregnancy. Results indicate that all were significantly effective in reducing GWG compared with the control group. More specifically, dietary interventions were the most effective in reducing weight gain, with a mean weight loss of -3.84kg compared with -0.72kg and -1.06kg for physical activity and the mixed (diet plus physical activity) approach, respectively. This finding is supported by Hill and colleagues' recent systematic review of theory based interventions to limit GWG. Included studies in this review reported an underpinning theory base and were classified as adopting a dietary, physical activity or mixed approach. Hill et al. concluded that studies which included a diet intervention were significantly more effective at limiting GWG.In 2011 Tanentsapf et al. reviewed the effect of dietary interventions alone for reducing GWG in normal weight, overweight and obese pregnant women. This review analysed 13 randomized controlled trials and quasi-randomized controlled trials with a dietary intervention to prevent excessive GWG in women. The review concluded that dietary interventions during pregnancy were effective in reducing GWG with an effect of -1.92kg (n=1434) compared with the control group.Tanentsapf et al. identified that trials differed in the conduct of the interventions with various diet and non-diet related components utilised. Dietary approaches were highly variable with some trials focusing only on calorie restriction and others included additional target macronutrient distribution for intake. Some trials further provided feedback based on maternal weight gain guidelines. Interventions also varied in delivery method with a variety of modes used, including face-to-face, in idual or group consultations and/or written correspondence. The frequency of communication, despite the type or mix, also changed from trial to trial with additional methods via telephone, posted materials, feedback or food diaries utilised. The inclusion of physical activity in addition to diet intervention was also common. Whilst the recent review by Tanentsapf et al. identified that dietary interventions are effective in reducing GWG, the review did not investigate the impact that different intervention components, delivery methods or dietary counselling approaches had on gestational weight management. It remains unclear as to which intervention components optimize GWG in women.The impact of lifestyle interventions has also been investigated in the postpartum period. The recent systematic review from van der Pligt et al. reported seven of 11 studies reviewed were successful in limiting PPWR. As with studies aimed at limiting GWG, interventions included in van der Pligt et al.'s review differed greatly in their conduct. Six of these seven studies included both dietary and physical activity components for the intervention, with the final successful study including a diet only intervention. Five of the successful studies recruited overweight or obese women only. Intervention time varied considerably in successful studies with some running for as little at ten days, and others up to six months.Bertz et al. demonstrated that their 12-week behavior modification intervention which targeted diet alone or diet and exercise, including two in idual sessions with a dietitian and physical therapist, provision of scales for weight self-monitoring and bi-weekly text messages was successful in achieving significant weight loss following the intervention, and sustained at one year. The diet intervention and the diet and exercise intervention yielded significant weight loss compared to the control. Following 12 weeks a reduction of -8.3 +/- 4.2kg for diet intervention and -6.9 +/- 3.0kg for diet and exercise was observed. Additionally after one year, the diet intervention showed -10.2 +/- 5.7kg reduction and -7.3 +/- 6.3kg for the diet and exercise intervention (p<0.001). Colleran et al. also found significant weight change results by implementing a 16-week intervention which consisted of weekly in idual sessions with a dietitian regarding calorie restriction, two additional home visits regarding exercise, weekly food diary completion and email support. The intervention group had greater weight loss compared to the control group (-5.8kg +/- 3.5kg vs -1.6kg +/- 5.4kg). It can be seen that various methods have been utilized in investigating the impact of diet and physical activity interventions on PPWR. The review by van der Pligt et al. highlights the impact successful lifestyle interventions can have on postpartum weight change. However, this review did not investigate the different intervention strategies utilized. It remains unclear as to the optimal setting, delivery method, diet strategy, contact frequency or intervention length to limit PPWR.Previous systematic reviews for both GWG and PPWR have focused on the effectiveness of lifestyle interventions as a whole for weight management in pregnant and postpartum women. And despite Tanentsapf et al.'s focus on dietary interventions for GWG, much is still unknown about the effectiveness of differing diet interventions over the antenatal and postpartum period. Specifically, the impact of differing diet intervention strategies on maternal weight gain is not known. Firstly, this systematic review will focus on whether weight management interventions which include a dietary component are effective in pregnant and postpartum women. In addition to this, this review will investigate the different intervention strategies utilized and their effectiveness in maternal weight management. A search of systematic review protocol databases has shown that there is no current review underway for this topic.
Publisher: The Endocrine Society
Date: 06-2009
DOI: 10.1210/JC.2008-2257
Abstract: Clinical prediction of preterm delivery is largely ineffective, and the mechanism mediating progesterone (P) withdrawal and estrogen activation at the onset of human labor is unclear. Our objectives were to determine associations of rates of change of circulating maternal CRH in midpregnancy with preterm delivery, CRH with estriol (E3) concentrations in late pregnancy, and predelivery changes in the ratios of E3, estradiol (E2), and P. A cohort of 500 pregnant women was followed from first antenatal visits to delivery during the period 2000-2004 at John Hunter Hospital, New South Wales, Australia, a tertiary care obstetric hospital. Unselected subjects were recruited (including women with multiple gestations) and serial blood s les obtained. CRH daily percentage change in term and preterm singletons at 26 wk, ratios E3/E2, P/E3, and P/E2 and the association between E3 and CRH concentrations in the last month of pregnancy (with spontaneous labor onset) were assessed. CRH percentage daily change was significantly higher in preterm than term singletons at 26 wk (medians 3.09 and 2.73 P = 0.003). In late pregnancy, CRH and E3 concentrations were significantly positively associated (P = 0.003). E3/E2 increased, P/E3 decreased, and P/E2 was unchanged in the month before delivery (medians: E3/E2, 7.04 and 10.59, P < 0.001 P/E3, 1.55 and 0.98, P < 0.001 P/E2, 11.78 and 10.79, P = 0.07). The very rapid rise of CRH in late pregnancy is associated with an E3 surge and critically altered P/E3 and E3/E2 ratios that create an estrogenic environment at the onset of labor. Our evidence provides a rationale for the use of CRH in predicting preterm birth and informs approaches to delaying labor using P supplementation.
Publisher: Georg Thieme Verlag KG
Date: 1987
Abstract: To determine if normal balance is restored to the hypothalamic-pituitary-adrenal axis after pregnancy, we compared the dexamethasone suppressibility of plasma cortisol in women four days after delivery of their infant, with that of nonpregnant women. Plasma concentrations of cortisol before dexamethasone administration were similar in the post-partum women and in women taking oestrogen contraceptives, but both were higher than in normally cycling women. After dexamethasone, plasma cortisol in the post-partum women was significantly higher than in both oestrogen-taking and normally cycling nonpregnant women. The reduced dexamethasone-suppressibility of plasma cortisol, which is characteristic of pregnancy, extends into the post-partum period.
Publisher: Wiley
Date: 11-2001
Publisher: Elsevier BV
Date: 07-2022
Abstract: Complications from placental malaria cause poor pregnancy outcomes, including low birthweight, preterm delivery, and stillbirths. Many of these complications are driven by maternal innate proinflammatory responses to the sequestration of Plasmodium falciparum in the placenta. However, recent studies show that, in reaction to maternal innate immune responses that are detrimental to the fetus, the fetus mounts innate immune counter-responses that ameliorate pregnancy outcomes. Such fetal-maternal conflict in placental malaria has potential for pharmacologic modulation for better pregnancy outcomes. Here, we discuss placental malaria pathogenesis, its complications, and the role of innate immunity and fetal-maternal innate immune conflict in placental malaria. Finally, we discuss pharmacologic immunomodulatory strategies and agents with the potential to improve placental malaria outcomes.
Publisher: Cold Spring Harbor Laboratory
Date: 10-10-2022
DOI: 10.1101/2022.10.07.22280820
Abstract: Caesarean section has a significant role in reducing maternal and neonatal mortality. A linked analysis of population and health facility data is valuable to map and identify caesarean section use and associated factors. This study aimed to identify geographic variation and associated factors of caesarean delivery in Ethiopia. Linked data analysis of the 2016 Ethiopia Demographic and Health Survey (EDHS) and the 2014 Ethiopian Service Provision Assessment Plus (ESPA+) survey was performed. Spatial analysis was conducted to identify geographic variations and factors associated with caesarean delivery. Hierarchical Bayesian analysis was also performed to identify factors associated with caesarean delivery using the SAS MCMC procedure. Women’s age and education, household wealth, parity, antenatal care (ANC) visits, and distance to caesarean section facility were associated with caesarean delivery use. Women who had ≥4 ANC visits were 4.67 (95% Credible Interval (CrI): 2.17, 9.43) times more likely to have caesarean delivery compared to those who had no ANC visits. Women who had education and were from rich households were also 2.80 (95% CrI: 1.83, 4.19) and 1.80 (95% CrI: 1.08, 2.84) times more likely to have caesarean deliveries relative to women who had no education and were from poor households, respectively. A one-kilometer increase in distance to a caesarean section facility was associated with an 88% reduction in the odds of caesarean delivery (Adjusted Odds Ratio (AOR) = 0.12, 95% CrI: 0.01, 0.78). Hotspots of high caesarean section rates were observed in Addis Ababa, Dire Dawa, and the Harari region. In addition, women’s age at first childbirth and ≥4 ANC visits showed significant spatially varying relations between caesarean delivery use across Ethiopia. Caesarean section is a lifesaving procedure, and it is essential to narrow disparities to reduce maternal and neonatal mortality and avoid unnecessary procedures.
Publisher: Informa UK Limited
Date: 12-2009
Publisher: The Endocrine Society
Date: 27-07-2017
DOI: 10.1210/ER.2016-1133
Abstract: Infertility affects a remarkable one in four couples in developing countries. Psychological stress is a ubiquitous facet of life, and although stress affects us all at some point, prolonged or unmanageable stress may become harmful for some in iduals, negatively impacting on their health, including fertility. For instance, women who struggle to conceive are twice as likely to suffer from emotional distress than fertile women. Assisted reproductive technology treatments place an additional physical, emotional, and financial burden of stress, particularly on women, who are often exposed to invasive techniques associated with treatment. Stress-reduction interventions can reduce negative affect and in some cases to improve in vitro fertilization outcomes. Although it has been well-established that stress negatively affects fertility in animal models, human research remains inconsistent due to in idual differences and methodological flaws. Attempts to isolate single causal links between stress and infertility have not yet been successful due to their multifaceted etiologies. In this review, we will discuss the current literature in the field of stress-induced reproductive dysfunction based on animal and human models, and introduce a recently unexplored link between stress and infertility, the gut-derived hormone, ghrelin. We also present evidence from recent seminal studies demonstrating that ghrelin has a principal role in the stress response and reward processing, as well as in regulating reproductive function, and that these roles are tightly interlinked. Collectively, these data support the hypothesis that stress may negatively impact upon fertility at least in part by stimulating a dysregulation in ghrelin signaling.
Publisher: Springer Science and Business Media LLC
Date: 30-01-2020
DOI: 10.1038/S41598-020-58425-5
Abstract: Nerves are emerging regulators of cancer progression and in several malignancies innervation of the tumour microenvironment is associated with tumour aggressiveness. However, the innervation of thyroid cancer is unclear. Here, we investigated the presence of nerves in thyroid cancers and the potential associations with clinicopathological parameters. Nerves were detected by immunohistochemistry using the pan-neuronal marker PGP9.5 in whole-slide sections of papillary thyroid cancer (PTC) (n = 75), compared to follicular thyroid cancer (FTC) (n = 13), and benign thyroid tissues (n = 26). Nerves were detected in most normal thyroid tissues and thyroid cancers, but nerve density was increased in PTC (12 nerves/cm 2 [IQR 7–21]) compared to benign thyroid (6 nerves/cm 2 [IQR: 3–10]) (p = 0.001). In contrast, no increase in nerve density was observed in FTC. In multivariate analysis, nerve density correlated positively with extrathyroidal invasion (p 0.001), and inversely with tumour size (p 0.001). The majority of nerves were adrenergic, although cholinergic and peptidergic innervation was detected. Perineural invasion was present in 35% of PTC, and was independently associated with extrathyroidal invasion (p = 0.008). This is the first report of infiltration of nerves into the tumour microenvironment of thyroid cancer and its association with tumour aggressiveness. The role of nerves in thyroid cancer pathogenesis should be further investigated.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.AJOG.2018.10.094
Abstract: Low birthweight is more common in infants of indigenous (Aboriginal and/or Torres Strait Islander) than of White Australian mothers. Controversy exists on whether fetal growth is normally different in different populations. We sought to determine the relationships of birthweight, birthweight percentiles, and smoking with perinatal outcomes in indigenous vs nonindigenous infants to determine whether the White infant growth charts could be applied to indigenous infants. Data were analyzed for indigenous status, maternal age and smoking, and perinatal outcomes in 45,754 singleton liveborn infants of at least 20 weeks gestation or 400 g birthweight delivered in New South Wales, Australia, between June 2010 and July 2015. Indigenous infants (n=6372 14%) had a mean birthweight 67 g lower than nonindigenous infants (P<.0001 with adjustment for infant sex and maternal body mass index). Indigenous mean birthweight percentile was 4.2 units lower (P<.0001). Adjustment for maternal age, smoking, body mass index, and infant sex reduced the difference in birthweight ercentiles to nonsignificance (12 g P=.07). Disparities exist between indigenous and non-indigenous Australian infants for birthweight, birthweight percentile, and adverse outcome rates. Adjustment for smoking and maternal age removed any significant difference in birthweights and birthweight percentiles for indigenous infants. Our data indicate that birthweight percentiles should not be adjusted for indigenous ethnicity because this normalizes disadvantage because White and indigenous Australians have erged for approximately 50,000 years, it is likely that the same conclusions apply to other ethnic groups. The disparities in birthweight percentiles that are associated with smoking will likely perpetuate indigenous disadvantage into the future because low birthweight is linked to the development of chronic noncommunicable disease and poorer educational attainment similar problems may affect other indigenous populations.
Publisher: The Endocrine Society
Date: 21-10-2009
DOI: 10.1210/EN.2009-0348
Abstract: As human pregnancy advances, CRH increases exponentially and is hypothesized to trigger the transition from myometrial quiescence to active contractions at labor. Paradoxically, CRH stimulates cAMP production, suggesting it should cause relaxation. To evaluate CRH as a mediator of quiescence, the effect of CRH on contractions in preterm and term myometria with concurrent progesterone (P4) was determined. In late gestation, we hypothesized that high concentrations of CRH down-regulate agonist-activated-cAMP relaxatory pathways and that increased phosphodiesterase (PDE) activity induces heterologous down-regulation of agonist-activated-cAMP pathways. CRH caused dose-dependent relaxation of spontaneously contracting myometrial strips of 31 ± 8% (mean ± sem n = 12) and 35 ± 20% (n = 3) in term and preterm s les, respectively. CRH with P4 pretreatment caused a 40 ± 13% (n = 4) reduction in contractility, whereas in matched s les, CRH alone exerted a 26 ± 6% (n = 4) reduction, with a shift of CRH dose-response curves (P & 0.01, ANOVA). Pretreatment of strips with 10−7m CRH did not attenuate relaxation induced by subsequent CRH (n = 3) or salbutamol (β2-agonist) treatment (n = 9). PDE inhibition by rolipram showed a 2.2- and 1.5-fold increase in maximal relaxation induced by CRH and salbutamol, respectively, with a shift of both dose-response curves (P & 0.05 and P & 0.01, ANOVA). In conclusion, CRH at physiological concentrations acts synergistically with P4 contributing to myometrial quiescence. P4 withdrawal may reduce CRH-mediated relaxation. Our functional model does not support homologous or heterologous down-regulation of agonist-stimulated-cAMP pathways by high CRH concentrations. PDE inhibition potentiates CRH and salbutamol-induced relaxation. Up-regulation of PDEs, through chronic cAMP elevation by CRH, could provide a mechanism for down-regulation of agonist-stimulated-cAMP pathways at term.
Publisher: IEEE
Date: 07-2007
Publisher: Bioscientifica
Date: 04-2001
Abstract: Corticotrophin-releasing hormone (CRH), the hypothalamic peptide that controls function of the pituitary-adrenal axis in response to stress, is expressed in abundance in the human placenta and is present in high concentrations in maternal and fetal plasma during late pregnancy. A number of lines of evidence now imply a role for this hormone in the control of parturition and fetal maturation in humans. It has been proposed that CRH, through interactions with oestrogen, adrenal steroids, prostaglandins and oxytocin, establishes positive-feedback loops that initiate parturition and labour. Excessive production of placental CRH has also been linked to preterm labour. However, there are a number of significant gaps in our knowledge of the function of this peptide in pregnancy. This review examines current evidence regarding the putative role of CRH in human parturition.
Publisher: Public Library of Science (PLoS)
Date: 18-07-2019
Publisher: Wiley
Date: 05-1981
DOI: 10.1111/J.1365-2265.1981.TB00636.X
Abstract: Thirteen patients with either Addison's disease, or Cushing's disease treated by bilateral adrenalectomy, were infused with the long-acting met-enkephalin analogue DAMME. In patients with Addison's disease significant and pronounced falls in ACTH and N- and C-terminal beta-LPH were seen chromatography suggested that beta-endorphin fell concomitantly. Three out of four patients with Cushing's disease who had not received pituitary irradiation, also showed a decrease in plasma ACTH and N- and C-terminal beta-LPH however, no change was seen in any of the irradiated patients. The changes were naloxone reversible. The levels of plasma met-enkephalin were normal and did not change after DAMME in any group of patients. These results are interpreted as suggesting that there are inhibitory opiate receptors controlling the release of ACTH, beta-LPH, and beta-endorphin.
Publisher: Springer Science and Business Media LLC
Date: 05-1995
DOI: 10.1038/NM0595-460
Abstract: We report the existence of a 'placental clock', which is active from an early stage in human pregnancy and determines the length of gestation and the timing of parturition and delivery. Using a prospective, longitudinal cohort study of 485 pregnant women we have demonstrated that placental secretion of corticotropin-releasing hormone (CRH) is a marker of this process and that measurement of the maternal plasma CRH concentration as early as 16-20 weeks of gestation identifies groups of women who are destined to experience normal term, preterm or post-term delivery. Further, we report that the exponential rise in maternal plasma CRH concentrations with advancing pregnancy is associated with a concomitant fall in concentrations of the specific CRH binding protein in late pregnancy, leading to a rapid increase in circulating levels of bioavailable CRH at a time that coincides with the onset of parturition, suggesting that CRH may act directly as a trigger for parturition in humans.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.BPOBGYN.2018.03.005
Abstract: Preterm birth remains a major obstetric problem with ramifications that extend beyond immediate health and safety concerns for the newborn to include massive societal and economic burden. Although three quarters of preterm birth-related deaths could be prevented with cost-effective interventions, there has been little progress towards achieving sustained tocolysis that translates into improved outcomes for the newborn. With private enterprise reluctant to venture into the sphere of tocolysis, due to potential litigation, advances in the field may fall to new approaches using existing tocolytic resources more effectively. An emerging approach is the utilisation of nanoparticles, which have been established as versatile drug carriers with the power to modify the pharmacokinetics of entrapped therapeutics. In this article, we examine the development of nanoparticle-based drug delivery in pregnancy, with a focus on new approaches to therapeutics for preterm birth and modifying the labour process more generally.
Publisher: Elsevier BV
Date: 05-2011
DOI: 10.1016/J.BIOCEL.2011.02.007
Abstract: A relationship between cytotrophoblast differentiation (syncytialisation) and apoptosis is hypothesised to exist, but has not been clearly determined. To address this, we explored the effects of cAMP, an inducer of syncytialisation, on human choriocarcinoma cell differentiation and viability under three different culture conditions related to erse survival status: no serum, 10% fetal calf serum or 10% charcoal-stripped fetal calf serum. 8-Br-cAMP increased BeWo cell viability in culture media without serum, but viability was decreased in a dose- and time-dependent manner when serum was present. The appearance of apoptotic nuclei fragments were only observed when BeWo cells were cultured in media containing serum combined with 8-Br-cAMP treatment. In addition, the ratio of FasL to Fas expression following treatment with 8-Br-cAMP increased by 20-fold in 10% charcoal-stripped fetal calf serum media and 65-fold 10% fetal calf serum media, and activation of caspase-3 also required media with serum. The markers of syncytialisation (syncytin 1 expression and human chorionic gonadotropin secretion) were induced significantly by 8-Br-cAMP, and were higher in 10% fetal calf serum media than in 10% charcoal-stripped fetal calf serum media, than in the absence of serum. Syncytia formation was stimulated by 8-Br-cAMP and this required serum in the media. We now show that factors contained within serum are necessary for cAMP-stimulated cytotrophoblast differentiation, that syncytialisation involves apoptotic events, and that a lack of serum based factors could switch the cellular program away from differentiation.
Publisher: The Endocrine Society
Date: 06-2002
Abstract: In human parturition, progesterone withdrawal and estrogen activation are not mediated by changes in progesterone and estrogen levels. Instead, these events could be facilitated by changes in the responsiveness of the myometrium to progesterone and estrogens via changes in PR and ER expression. We hypothesized that functional progesterone withdrawal occurs by increased expression of the type A PR (PR-A), which suppresses progesterone responsiveness, and that functional estrogen activation occurs by increased myometrial expression of ERalpha and/or ERbeta. To test this hypothesis we compared the abundance of mRNAs (assessed by quantitative RT-PCR) encoding PR-A, PR-B, ERalpha, and ERbeta in nonlaboring (n = 12) and laboring (n = 12) term human myometrium. PR-A, PR-B, the PR-A/PR-B mRNA ratio, and ERalpha mRNA were significantly increased in laboring myometrium, whereas ERbeta mRNA was low and unchanged. The PR-A/PR-B mRNA ratio correlated positively with ERalpha mRNA levels in nonlaboring myometrium and with HOXA10 mRNA levels in laboring myometrium. Because progesterone inhibits ERalpha and HOXA10 expression, these findings indicate that myometrial progesterone responsiveness is inversely related to the extent of expression of PR-A relative to PR-B. ERalpha mRNA levels correlated positively with cyclooxygenase type 2 and oxytocin receptor mRNA levels in nonlaboring myometrium, indicating that the increase in ERalpha expression is directly associated with the activation of contraction-associated genes and estrogen responsiveness. These data indicate that in the term human myometrium, responsiveness to progesterone is controlled by the expression of PR-A relative to PR-B and that a significant increase in this ratio underlies functional progesterone withdrawal. Our data also indicate that functional estrogen activation occurs by increased expression of ERalpha and is linked to functional progesterone withdrawal. Interaction between the PR and ER systems in the human myometrium may be critical for the control of human parturition and the coordination of progesterone withdrawal and estrogen activation required for parturition.
Publisher: Public Library of Science (PLoS)
Date: 30-06-2011
Publisher: Georg Thieme Verlag KG
Date: 17-11-2011
Abstract: With improved health care, the number of premature babies who survive to adulthood is expected to increase. The objective of this review is to determine whether premature infants have an increased risk of chronic kidney disease (CKD). A literature review was performed by searching PubMed (U.S. National Library of Medicine) and the Cochrane Library, using the keywords "prematurity," "kidney," "nephrogenesis," "oligonephropathy," and "kidney impairment." Articles published in English since 1990 were reviewed. Increasing evidence suggests that prematurity causes oligonephropathy independently of, and coexisting with, intrauterine growth restriction. Animal studies show that nephrogenesis continues for up to 3 weeks in extrauterine life, but with up to 18% abnormal glomeruli. Nephrogenesis is further impaired in preterm infants who develop renal impairment in the early postnatal period, which is estimated to be 8 to 24%. Premature infants are at risk for CKD. A larger longitudinal study is needed that follows up premature infants to determine the exact incidence of CKD. Until then, renal assessment in premature infants should be incorporated into follow-up guidelines, in addition to the current assessment of growth and neurodevelopmental outcomes. The cost implications to a comprehensive program, impact of early identification, and strategies to improve outcomes in this population are needed.
Publisher: Elsevier BV
Date: 02-2001
Publisher: Wiley
Date: 11-1979
DOI: 10.1111/J.1365-2265.1979.TB03108.X
Abstract: Apolipoprotein E (apo E) is responsible for the binding of very low density lipoprotein and chylomicron remnants to cellular receptors thereby removing them from circulation. We have isolated and determined the sequence of a cDNA encoding 285 amino acids and the entire 3' untranslated region of 112 nucleotides of mouse apo E. The remaining coding sequence was determined by sequencing mouse liver mRNA. Comparisons with rat and human apo E sequences showed a high degree of conservation although there were regions in each species that were characterized by unique insertions and deletions. Analysis of the sequence homologies within apo E revealed that the entire sequence is made up of repetitive units. The most primitive unit appeared to be an 11-nucleotide repeat within higher order repeats of 22 or 33 nucleotides. The 11-nucleotide unit -TCGGACGAGGC- is read in all three reading frames, and when tandemly repeated, it encodes the highly conserved amino acid sequence Xaa-(Glu/Asp)-(Glu/Asp)-Xaa-Arg-Xaa-Arg-Leu-Gly-Xaa-Xaa. We postulate that apo E and those other apolipoproteins related to it have arisen by duplications and subsequent modifications of this or a closely related 11-nucleotide ancestral sequence.
Publisher: Elsevier BV
Date: 03-1985
DOI: 10.1016/0304-3940(85)90305-2
Abstract: Seven women undergoing abdominal hysterectomy under halothane and nitrous oxide analgesia had plasma s les taken before, during and after surgery for assay of adrenocorticotrophin (ACTH), beta-endorphin, beta-lipotrophin and methionine (Met)-enkephalin immunoreactivity. Plasma ACTH, beta-endorphin and beta-lipotrophin all rose in parallel from the start of surgery and were unaffected by postoperative opiate analgesia. Plasma Met-enkephalin concentrations did not change significantly during the course of the surgery and immediate post-operative period, although the variance of the s les increased at the time of the first skin incision. These data indicate that the stress of surgery and post-operative pain, while producing marked elevations of proopiomelanocortin-derived peptides, are not associated with changes in plasma Met-enkephalin. These data exclude a role for circulating Met-enkephalin in the modulation of surgical pain but do not exclude such a role for beta-endorphin.
Publisher: Wiley
Date: 15-03-2010
Publisher: Wiley
Date: 12-2009
Publisher: Springer Science and Business Media LLC
Date: 30-10-2010
DOI: 10.1007/S00011-009-0102-Y
Abstract: Pregnancy can influence the course of maternal asthma, but the mechanisms are presently unknown. The aim of the present study was to access maternal immune cell profiles in the presence and absence of asthma and to determine the effect of pregnancy-derived factors on epithelial cell function. Cells from the human bronchial epithelial cell line BEAS-2B were treated with plasma from pregnant or nonpregnant asthmatic and nonasthmatic subjects. Cell culture supernatants were collected after 24 h and assayed for IL-6, IL-8, eotaxin, RANTES and sICAM-1 protein using ELISA. Maternal immune cell count and peripheral blood chemotactic response to plasma from pregnant and non-pregnant asthmatic subjects were also assessed. The presence of maternal asthma during pregnancy was associated with increased monocyte and neutrophil numbers, increased BEAS-2B cell production of IL-8 and sICAM-1 (P < 0.05) and increased chemotactic capacity relative to pregnant women without asthma. The results of this study suggest that circulating pregnancy-related factors enhance chemotactic mediators in epithelial cells in the presence of asthma. This may be one mechanism that contributes to pregnancy-induced changes in asthma.
Publisher: BMJ
Date: 07-07-2017
DOI: 10.1136/BJOPHTHALMOL-2016-308828
Abstract: Retinopathy of prematurity (ROP), a vasoproliferative disorder exclusive to premature infants is an important cause of childhood blindness. The number of premature infants surviving with this condition is expected to increase globally. Animal models of oxygen-induced retinopathy studies have shown vascular endothelial growth factor (VEGF) to be a key player in the pathogenesis of ROP. This has led to increased use of VEGF antagonist as an alternative treatment for ROP. The purpose of this systematic review is to determine the association between VEGF and ROP in human newborn. The literature review identified 12 studies to date which fulfilled the search criteria. Investigators used cord blood, serum, plasma and tissue s les to investigate the association between ROP and VEGF. Studies that measured VEGF in cord blood found mixed results, with low VEGF (at birth) associated with ROP in one study and no difference noted in two others. Mixed results were also seen in studies determining VEGF in postnatal venous s les. Four studies showed no difference in VEGF level between premature infants with and without ROP, one study showed an increased VEGF level in premature infants with ROP and another study found serum VEGF to be low in premature infants with ROP. The most recent study demonstrated an initial increase in serum VEGF followed by a decline at the time of treatment. These contradictory results indicate that we are yet to fully understand the role of VEGF in human premature infants and question the rationale of treating ROP with anti-VEGF. Anti-VEGF therapy results in systemic effect on serum VEGF levels for up to 2 months and this could have an effect on neurodevelopmental outcome. The effect of this on other developing organs is currently unknown. More studies are required to determine the mechanistic relationships between systemic VEGF and ROP in premature infants.
Publisher: Elsevier
Date: 2020
Publisher: MDPI AG
Date: 27-02-2018
DOI: 10.3390/NU10030273
Publisher: Wiley
Date: 2006
DOI: 10.1111/J.1440-1843.2006.00782.X
Abstract: The course of asthma may be altered during pregnancy with at least one-third of women experiencing a worsening of asthma and 20% having an exacerbation during pregnancy. This study used the novel proteomic technique, surface-enhanced laser desorption ionization-time of flight mass spectrometry to determine if the presence of asthma during pregnancy was associated with alterations in plasma proteins. Plasma collected from healthy (n = 23) and asthmatic (n = 27) pregnant women at 18 and 30 weeks gestation was applied to strong anion exchange (SAX2), weak cation exchange (WCX2) and immobilized metal affinity capture (IMAC-Cu(2+)) chips. Mass analysis was conducted using Ciphergen Protein Biology System IIc and significant differences in in idual peak intensities between groups determined. At 18 weeks gestation, 91 peaks were significantly different between pregnant women with and without asthma, representing 28% of the total peaks identified. At 30 weeks gestation, 51 peaks were significantly different. There were two peaks that were significantly different between groups at both 18 and 30 weeks gestation and expressed at a similar level at both time points. One was increased in asthmatics (MW = 6444 Da) whereas the other decreased in asthmatics compared with non-asthmatic women (MW = 1846 Da). This study demonstrated that there are differences in protein patterns between pregnant women with and without asthma. Other techniques are needed to define the molecular species and classify pathophysiological significance. Surface-enhanced laser desorption ionization-time of flight mass spectrometry has potential as a tool to monitor disease progression in situations such as pregnancy.
Publisher: Springer Science and Business Media LLC
Date: 2018
DOI: 10.1038/NATURE25149
Abstract: Fast radio bursts are millisecond-duration, extragalactic radio flashes of unknown physical origin. The only known repeating fast radio burst source-FRB 121102-has been localized to a star-forming region in a dwarf galaxy at redshift 0.193 and is spatially coincident with a compact, persistent radio source. The origin of the bursts, the nature of the persistent source and the properties of the local environment are still unclear. Here we report observations of FRB 121102 that show almost 100 per cent linearly polarized emission at a very high and variable Faraday rotation measure in the source frame (varying from +1.46 × 10
Publisher: Elsevier BV
Date: 09-2000
Publisher: Wiley
Date: 09-1987
DOI: 10.1111/J.1447-0756.1987.TB00276.X
Abstract: Mature microRNAs (miRNAs) are single-stranded RNAs that regulate post-transcriptional gene expression. In our previous study, we have shown that versican 3'UTR, a fragment of non-coding transcript, has the ability to antagonize miR-199a-3p function thereby regulating expression of the matrix proteins versican and fibronectin, and thus resulting in enhanced cell-cell adhesion and organ adhesion. However, the impact of this non-coding fragment on tumorigenesis is yet to be determined. Using computational prediction confirmed with in vitro and in vivo experiments, we report that the expression of versican 3'UTR not only antagonizes miR-199a-3p but can also lower its steady state expression. We found that expression of versican 3'UTR in a mouse breast carcinoma cell line, 4T1, decreased miR-199a-3p levels. The decrease in miRNA activity consequently translated into differences in tumor growth. Computational analysis indicated that both miR-199a-3p and miR-144 targeted a cell cycle regulator, Rb1. In addition, miR-144 and miR-136, which have also been shown to interact with versican 3'UTR, was found to target PTEN. Expression of Rb1 and PTEN were up-regulated synergistically in vitro and in vivo, suggesting that the 3'UTR binds and modulates miRNA activities, freeing Rb1 and PTEN mRNAs for translation. In tumor formation assays, cells transfected with the 3'UTR formed smaller tumors compared with cells transfected with a control vector. Our results demonstrated that a 3'UTR fragment can be used to modulate miRNA functions. Our study also suggests that miRNAs in the cancer cells are more susceptible to degradation, due to its interaction with a non-coding 3'UTR. This non-coding component of mRNA may be used retrospectively to modulate miRNA activities.
Publisher: Future Science Ltd
Date: 12-2007
DOI: 10.2144/000112594
Abstract: We describe a procedure for the simultaneous extraction of proteins and nucleic acids from the same experimental s le allowing for direct correlations between genetic, genomic, and proteomic data. This approach, using commercially available column-based nucleic acid extraction kits, requires no hazardous chemicals and is a quick, reliable, and consistent method for concomitant protein extraction. Buffer choice is critical to completely solubilize all proteins in the s le. Proteins solubilized in radioimmunoprecipitation assay (RIPA) buffer did not represent the entire profile when compared with conventionally extracted proteins using the same buffer at the one-dimensional (1-D) sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) level, however, proteins extracted from the columns and solubilized in a two-dimensional (2-D) electrophoresis lysis buffer showed a similar profile to conventionally extracted proteins when analyzed at both the 1-D and the 2-D level. We further showed that proteins extracted using these methods were compatible with Western blot analysis. This technique provides a simple and effective way to analyze protein and nucleic acids simultaneously from the same s le without affecting yield and quality.
Publisher: Cambridge University Press (CUP)
Date: 02-2019
DOI: 10.1017/S2040174418001125
Abstract: In Australia, there are two distinct populations, each with vastly disparate health outcomes: Aboriginal and Torres Strait Islander People and non-Aboriginal Australians. Aboriginal Australians have significantly higher rates of health and socioeconomic disadvantage, and Aboriginal babies are also more likely to be born low birth weight or growth restricted. The Developmental Origins of Health and Disease ( DOHaD ) hypothesis advocates that a sub-optimal intrauterine environment, often manifested as diminished foetal growth, during critical periods of foetal development has the potential to alter the risk of non-communicable disease in the offspring. A better understanding of the role of the intrauterine environment and subsequent developmental programming, in response to both transgenerational and immediate stimuli, in Aboriginal Australians remains a relatively unexplored field and may provide insights into the prevailing health disparities between Aboriginal and non-Aboriginal children. This narrative review explores the role of DOHaD in explaining the ongoing disadvantage experienced by Aboriginal People in today’s society through a detailed discussion of the literature on the association between foetal growth, as a proxy for the quality of the intrauterine environment, and outcomes in the offspring including perinatal health, early life development and childhood education. The literature largely supports this hypothesis and this review therefore has potential implications for policy makers not only in Australia but also in other countries that have minority and Indigenous populations who suffer disproportionate disadvantage such as the United States, Canada and New Zealand.
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1016/J.PLACENTA.2011.03.004
Abstract: The mechanisms that contribute to adverse outcomes for the neonate in pregnancies complicated by asthma may be mediated via changes in placental immune function. This study was designed to determine whether the presence of maternal asthma during pregnancy alters the placental pro-inflammatory immune response in vitro. A prospective cohort study of women with asthma (n = 22) and control (n = 11) subjects had placentae collected immediately after delivery. Placental explants were exposed to an immune challenge, lipopolysaccharide, in the presence and absence of cortisol in vitro. Cytokines, glucocorticoid receptor α (GR α) and p38 MAPK protein were measured. Placentae of control pregnancies had an increase in pro-inflammatory cytokine production over a 24 h period. Placentae from pregnancies complicated by maternal asthma had a reduced pro-inflammatory cytokine response to an immune challenge relative to the controls especially in relation to the production of interleukin (IL)-1β and TNFα regardless of fetal sex. Cortisol inhibition of placental cytokine production was dependent on timing of exposure, fetal sex and presence and absence of asthma. GRα and p38 MAPK protein expression did not appear to contribute to differences in response to endotoxin or cortisol. Maternal asthma during pregnancy induces a hyposensitive inflammatory state in the placenta which is regulated by cortisol in a sexually dimorphic manner.
Publisher: Elsevier BV
Date: 10-2002
DOI: 10.1016/S0167-0115(02)00105-2
Abstract: The mechanisms regulating human parturition and labor remain unknown. This ignorance is expensive as preterm birth is responsible for 70% of neonatal mortality and 50% of cerebral palsy. Methods for the prediction of preterm birth and treatments for women in preterm labor have poor efficacy reflecting our limited knowledge of the mechanisms involved. Recent research has supported the view that parturition is a cascade of events that commences early in pregnancy and involves the mother, fetus, placenta, membranes, cervix and myometrium. Although a number of the key hormones and proteins involved have been identified, the relationships between these factors in time and tissues remain unclear. Placental production of Corticotropin-releasing hormone (CRH) is proposed as an early event regulating the cascade of events. Central to the onset of parturition will be a mechanism for progesterone withdrawal and estrogen activation in human. Two forms of progesterone receptor with opposing actions exist in the human myometrium. Progesterone receptor A (PR-A) is a dominant negative repressor of progesterone receptor B (PR-B). Preliminary studies strongly support the hypothesis that the onset of human parturition is initiated by rising concentrations of PR-A in the myometrium.
Publisher: Wiley
Date: 04-1991
DOI: 10.1111/J.1365-2826.1991.TB00262.X
Abstract: Abstract Corticotropin-releasing hormone and arginine vasopressin are known to interact in stimulating secretion of adrenocorticotropin-related peptides from corticotropes. However, the mechanism mediating this interaction is uncertain. Recently, evidence has been provided using a reverse haemolytic plaque assay that in rat pituitary cells, arginine vasopressin potentiates the effects of corticotropin-releasing hormone by increasing the percentage of target cells that secrete adrenocorticotropin. To determine whether a similar mechanism also operates in the sheep corticotrope, which is reportedly more sensitive to arginine vasopressin than that of the rat, a reverse haemolytic plaque assay for beta-endorphin secretion was used to study the response of ovine corticotropes to stimulation by increasing doses of corticotropin-releasing hormone or arginine vasopressin (0.1 nM to 10.0 nM) alone or in combination. In the reverse haemolytic plaque assay, beta-endorphin antiserum at 1:50 and complement at 1:10 were found to be optimal dilutions for plaque formation. A concentration-dependent response curve to corticotropin-releasing hormone was obtained with a significant increase in plaque area from basal to reach maximal levels at 1.0 nM. Arginine vasopressin also stimulated an increase in plaque area, however, plaques formed were significantly smaller than those caused by corticotropin-releasing hormone. Since in the reverse haemolytic plaque assay, plaque area is related to the amount of hormone secreted by the cell, results demonstrate that although corticotropin-releasing hormone and arginine vasopressin both stimulate beta-endorphin secretion from ovine corticotropes, corticotropin-releasing hormone is a more potent secretagogue than arginine vasopressin in that it causes the formation of significantly larger plaques. The addition of arginine vasopressin to low concentrations of corticotropin-releasing hormone caused plaque areas to reach maximal levels at 0.1 nM whereas these levels were only attained at 1.0 nM when corticotropin-releasing hormone was used alone. Therefore, arginine vasopressin interacts with corticotropin-releasing hormone to increase corticotrope responses by increasing their secretory response to corticotropin-releasing hormone. These data are consistent with previous work suggesting that arginine vasopressin increases the expression of corticotropin-releasing hormone receptors on the corticotrope cell surface. However, no significant increase in the percentage of plaque-forming cells was seen with either corticotropin-releasing hormone or arginine vasopressin alone or in combination implying that there was no recruitment of previously non-secreting cells.
Publisher: Elsevier BV
Date: 05-2007
Publisher: Springer Science and Business Media LLC
Date: 03-01-2022
DOI: 10.1186/S12887-021-03058-4
Abstract: Globally, the burden of perinatal mortality is high. Reliable measures of perinatal mortality are necessary for planning and assessing prenatal, obstetric, and newborn care services. However, accurate record-keeping is often a major challenge in low resource settings. In this study we aimed to assess the utility of delivery ward register data, captured at birth by healthcare providers, to determine causes of perinatal mortality in one specialized and one general hospital in south Ethiopia. Three years (2014–2016) of delivery register for 13,236 births were reviewed from July 12 to September 29, 2018, in two selected hospitals in south Ethiopia. Data were collected using a structured pretested data extraction form. Descriptive statistics assessed early neonatal mortality rate, stillbirth rate, perinatal mortality rate and causes of neonatal deaths. Factors associated with early neonatal deaths and stillbirths were examined using logistic regression. The adjusted odds ratios with a 95% confidence interval were reported to show the strength of the association. The perinatal mortality ratio declined from 96.6 to 75.5 per 1000 births during the three-year study period. Early neonatal mortality and stillbirth rates were 29.3 per 1000 live births and 55.2 per 1000 total births, respectively. The leading causes of neonatal death were prematurity 47.5%, and asphyxia 20.7%. The cause of death for 15.6% of newborns was not recorded in the delivery registers. Similarly, the cause of neonatal morbidity was not recorded in 1.5% of the delivery registers. Treatment given for 94.5% of neonates were blank in the delivery registers, so it is unknown if the neonates received treatment or not. Factors associated with increased early neonatal deaths were maternal deaths and complications, vaginal births, APGAR scores less than 7 at five minutes and low birth weight (2500 g). Maternal deaths and complications and vaginal births were associated with increased stillbirths. Our findings show that an opportunity exists to identify perinatal death and newborn outcomes from the delivery ward registers, but some important neonatal outcomes were not recorded/missing. Efforts towards improving the medical record systems are needed. Furthermore, there is a need to improve maternal health during pregnancy and birth, especially neonatal care for those neonates who experienced low APGAR scores and birth weight to reduce the prevalence of perinatal deaths.
Publisher: Springer Science and Business Media LLC
Date: 27-11-2019
DOI: 10.1186/S12902-019-0457-1
Abstract: Nerves and neurotrophic growth factors are emerging promoters of cancer growth. The precursor for Nerve Growth Factor (proNGF) is overexpressed in thyroid cancer, but its potential role as a clinical biomarker has not been reported. Here we have examined the value of proNGF as a serum and biopsy-rinse biomarker for thyroid cancer diagnosis. Patients presenting for thyroid surgery or biopsy were enrolled in separate cohorts examining serum ( n = 204, including 46 cases of thyroid cancer) and biopsy-rinse specimens ( n = 188, including 26 cases of thyroid cancer). ProNGF levels in clinical s les were analysed by ELISA. Univariate and multivariate statistical analyses were used to compare proNGF levels with malignancy status and clinicopathological parameters. ProNGF was not detected in the majority of serum s les (176/204, 86%) and the detection of proNGF was not associated with thyroid cancer diagnosis. In the few cases where proNGF was detected in the serum, thyroidectomy did not affect proNGF concentration, demonstrating that the thyroid was not the source of serum proNGF. Intriguingly, an association between hyperthyroidism and serum proNGF was observed (OR 3.3, 95% CI 1.6–8.7 p = 0.02). In biopsy-rinse, proNGF was detected in 73/188 (39%) cases, with no association between proNGF and thyroid cancer. However, a significant positive association between follicular lesions and biopsy-rinse proNGF was found (OR 3.3, 95% CI 1.2–8.7, p = 0.02). ProNGF levels in serum and biopsy-rinse are not increased in thyroid cancer and therefore proNGF is not a clinical biomarker for this condition.
Publisher: Wiley
Date: 2001
Publisher: Wiley
Date: 1981
DOI: 10.1111/J.1365-2265.1981.TB00369.X
Abstract: Eight male patients with hypogonadotrophic hypogonadism were treated with injections of a long acting LHRH analogue, HOE 766. Six of the patients were on daily subcutaneous injections of 5 microgram of this analogue at the start of this study and were changed to alternate-daily injections of the same dose for 1-3 months. They were then treated with twice-daily injections of 0.5 microgram HOE 766, as was another subject not previously treated. The HOE 766 twice-daily was given alone for 1 or 2 months and then sex steroid replacement therapy was added to this for a further 4-5 months. There was no clinical improvement or rise in plasma testosterone levels until sex steroid therapy was commenced. Basal LH and FSH levels and peak responses to 100 microgram LHRH remained low throughout the study. It is concluded that these variations in dose and interval of administration do not overcome the lack of pituitary response which is a feature of prolonged treatment with LHRH analogues.
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.AJOG.2015.06.040
Abstract: The human uterus has no pacemaker or motor innervation, yet develops rhythmic, powerful contractions that increase intrauterine pressure to dilate the cervix and force the fetus through the pelvis. To achieve the synchronous contractions required for labor, the muscle cells of the uterus act as independent oscillators that become increasingly coupled by gap junctions toward the end of pregnancy. The oscillations are facilitated by changes in resting membrane potential that occur as pregnancy progresses. Reductions of potassium channels in the myocyte membranes in late pregnancy prolong myocyte action potentials, further facilitating transmission of signals and recruitment of neighboring myocytes. Late in pregnancy prostaglandin production increases leading to increased myocyte excitability. Also late in pregnancy myocyte actin polymerizes allowing actin-myosin interactions that generate force, following myocyte depolarization, calcium entry, and activation of myosin kinase. Labor occurs as a consequence of the combination of increased myocyte to myocyte connectivity, increased depolarizations that last longer, and activated intracellular contractile machinery. During labor the synchronous contractions of muscle cells raise intrauterine pressure to dilate the cervix in a process distinct from peristalsis. The synchronous contractions occur in a progressively larger region of the uterine wall. As the size of the region increases with increasing connectivity, the contraction of that larger area leads to an increase in intrauterine pressure. The resulting increased wall tension causes myocyte depolarization in other parts of the uterus, generating widespread synchronous activity and increased force as more linked regions are recruited into the contraction. The emergent behavior of the uterus has parallels in the behavior of crowds at soccer matches that sing together without a conductor. This contrasts with the behavior of the heart where sequential contractions are regulated by a pacemaker in a similar way to the actions of a conductor and an orchestra.
Publisher: Cambridge University Press (CUP)
Date: 11-2007
DOI: 10.1017/S0965539507002033
Abstract: One of the most important stages of pregnancy is the activation of uterine contractions that result in the expulsion of the fetus. The timely onset of labour is clearly important for a healthy start to life but incomplete understanding of the precise mechanisms regulating labour onset have prohibited the development of effective and safe treatments for preterm labour. This review explores the activation of the myometrium at labour onset, focussing on mechanisms of uterine contractility, including those proteins that play an important role in smooth muscle contractility. The review primarily focuses on human work but in the absence of human data describes animal studies. A broad overview of myometrial contraction mechanisms is provided before discussing more detailed aspects and identifying areas where uncertainty remains. Also discussed is the recent application of ‘omics’ based approaches to parturition research, which has facilitated an increase in the understanding of myometrial activation.
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.MVR.2019.04.005
Abstract: The link between in utero and early life insults and the development of chronic illness remains to be fully understood, but there is increasing data to indicate that microvasculature pathology plays an important mechanistic role. Currently available data indicate that retinal microvasculature changes are detectable in children as young as six years of age, however, there are no data for younger children. We present retinal microvasculature measurement from the first two years of life. Retinal images suitable for analysis were available from 18 infants in our proof-of-concept study. The mean and standard deviation (SD) for birth weight and gestation was 3410 (384) g and 39.1(1.4) weeks, respectively. Retinal vessel calibres were summarized as the mean(SD) central retinal arteriolar equivalent (CRAE) at six months of age was 156 (32) μm, increased to 175 (75) μm by 12 months and a slightly declined by 24 months of age to 168 (50) μm. In a similar pattern, mean(SD) central retinal venular equivalent (CRVE) at six months was 211 (19) μm, increased to 238 (25) μm by 12 months of age followed by a slight decline at 24 months of age to 222 (36) μm. The arterio-venous ratio and tortuosity index remained the same at 6, 12 and 24 months. Findings from this study could help future investigators better understand early microvasculature changes and adaptation that occur early in life.
Publisher: Elsevier
Date: 1998
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.PSYNEUEN.2015.09.019
Abstract: The maternal hypothalamic-pituitary-adrenal-axis (HPAA) undergoes dramatic activation during pregnancy. Increased cortisol and corticotrophin-releasing-hormone (CRH) associate with low birthweight and preterm labor. In non-pregnant obesity, the HPAA is activated but circulating cortisol levels are normal or lower than in lean women. We hypothesized that maternal cortisol levels would be lower in obese pregnancy, and would associate with increased fetal size and length of gestation. Fasting serum cortisol was measured at 16, 28 and 36 weeks gestation and at 3-6 months postpartum in 276 severely obese and 135 lean women. In a subset of obese (n=20) and lean (n=20) we measured CRH, hormones that regulate bioavailable cortisol (corticosteroid-binding-globulin, estradiol, estriol, and progesterone). Urinary glucocorticoid metabolites were measured in pregnant (obese n=6, lean n=5) and non-pregnant (obese n=7, lean n=7) subjects. Maternal cortisol and HPAA hormones were lower in obese pregnancy. Total urinary glucocorticoid metabolites increased significantly in lean pregnancy, but not in obese. Lower maternal cortisol in obese tended to be associated with increased birthweight (r=-0.13, p=0.066). In obese, CRH at 28 weeks correlated inversely with gestational length (r=-0.49, p=0.04), and independently predicted gestational length after adjustment for confounding factors (mean decrease in CRH of -0.25 pmol/L (95% CI -0.45 to -0.043 pmol/L) per/day increase in gestation). In obese pregnancy, lower maternal cortisol without an increase in urinary glucocorticoid clearance may indicate a lesser activation of the HPAA than in lean pregnancy. This may offer a novel mechanism underlying increased birthweight and longer gestation in obese pregnancy.
Publisher: The Endocrine Society
Date: 2002
Abstract: Males and females have a significantly different life expectancy because of the cardioprotective effects of estrogen. The mechanisms that result in this difference between the sexes are not fully understood. However, stress is a contributing factor to the development of cardiovascular disease, and stress-related factors derived from central or peripheral sources may have differential effects in the modulation of cardiovascular function in males and females. CRH is a central modulator of the stress response and is known to have vasodilator effects in a number of vascular beds. We have examined whether CRH has vasodilator effects in human skin and whether this effect is different between males and females using laser Doppler and iontophoresis. CRH (1 nm) had vasodilatory effects in the skin circulation of both premenopausal females (n = 6) and age-matched males (n = 5), but CRH-induced dilation was significantly more potent in females than males. Acetylcholine-(1 nm) and sodium nitroprusside- (0.74 nm) induced dilation was not significantly different between males (n = 6) and females (n = 6). This is the first study to demonstrate that CRH acts locally as a vasodilator in human skin circulation and that this response is augmented in premenopausal females. The mechanism by which CRH causes dilation in human skin is presently unknown. However, these data suggest that CRH-induced dilation may be one mechanism by which cardiovascular risk is reduced in premenopausal women.
Publisher: Public Library of Science (PLoS)
Date: 02-02-2017
Publisher: Wiley
Date: 17-02-2015
DOI: 10.1111/JDV.13035
Publisher: The Endocrine Society
Date: 08-1994
DOI: 10.1210/JCEM.79.2.7913933
Abstract: Human placenta synthesizes and secretes large amounts of CRH during the second and third trimesters. In the hypothalamus, nitric oxide (NO) has been reported to affect CRH release. We studied the effect of NO on the regulation of placental CRH secretion. The effect of the NO donor sodium nitroprusside (SNP) on basal and KCl-stimulated CRH release was examined in cultured human syncytiotrophoblasts. CRH secretion and intracellular concentrations of cGMP, calmodulin-dependent protein kinase (CaM-PK), protein kinase-G (PKG), protein kinase-C, and cAMP-dependent protein kinase holoenzyme were measured under basal conditions and after treatment with a depolarizing concentration of KCl and with SNP. The results showed that depolarization (3 h) increased CRH release 4-fold (from basal value of 5.16 +/- 0.65 to 19.31 +/- 4.46 fmol/10(6) cells) SNP (100 mumol/L) decreased both basal (0.42 +/- 0.21 fmol/10(6) cells) and KCl-stimulated CRH release (0.94 +/- 0.32 fmol/10(6) cells). KCl also increased the activity of CaM-PK in the cell membrane and both cytosolic and membrane PKG activity, whereas the activities of protein kinase-C and cAMP-dependent protein kinase holoenzyme were unchanged. SNP increased intracellular cGMP concentrations after 10, 60, and 180 min. Methylene blue (100 mumol/L), a guanylate cyclase inhibitor, blocked the inhibitory effects of SNP on CRH release. These results suggest that NO exerts inhibitory effects on both basal and KCl-stimulated CRH release from placental syncytiotrophoblasts through a cGMP-mediated pathway. In addition, as KCl-induced changes in the cell membrane were blocked by SNP, CaM-PK may be involved in KCl-stimulated CRH release. KCl may also sensitize the inhibitory pathway involved in the regulation of CRH release by increasing cellular PKG levels. The effects of KCl and SNP on CRH release are more complex than simple activation of CaM-PK and PKG activity, as other cellular signal transduction pathways are also modulated.
Publisher: Springer Science and Business Media LLC
Date: 27-03-2008
Publisher: Wiley
Date: 07-04-2017
DOI: 10.1111/AJO.12618
Abstract: Pregnancy can be a stressful time for many women. There is le evidence of numerous physical and mental health inequities for Indigenous Australians. For those Indigenous women who are pregnant, it is established that there is a higher incidence of poor physical perinatal outcomes when compared with non-Indigenous Australians. However, little evidence exists that examines stressful events and post-traumatic stress disorder (PTSD) symptoms in pregnant women who are members of this community. To quantify the rates of stressful events and PTSD symptoms in pregnant Indigenous women. One hundred and fifty rural and remote Indigenous women were invited to complete a survey during each trimester of their pregnancy. The survey measures were the stressful life events and the Impact of Events Scale. Extremely high rates of PTSD symptoms were reported by participants. Approximately 40% of this group exhibited PTSD symptoms during their pregnancy with mean score 33.38 (SD = 14.37) significantly higher than a study of European victims of crisis, including terrorism attacks (20.6, SD = 18.5). The extreme levels of PTSD symptoms found in the women participating in this study are likely to result in negative implications for both mother and infant. An urgent response must be mounted at government, health, community development and research levels to address these findings. Immediate attention needs to focus on the development of interventions to address the high levels of PTSD symptoms that pregnant Australian Indigenous women experience.
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.PNPBP.2012.10.005
Abstract: Postnatal depression is common and negatively affects the mother-baby relationship oxytocin has been found to have positive effects on parenting behavior. We hypothesize that intranasal administration of oxytocin to mothers with depression will influence their parenting related expressed emotion, creating a better basis for sensitive parenting. Twenty-five postnatally depressed mothers with infants less than one year participated in a randomized, double-blind, placebo controlled within-subject clinical study in 2011. Mothers attended an out-patient perinatal psychiatry setting in NSW, Australia. They received 24 IU of oxytocin alternating with placebo approximately one week apart in random order, prior to completing outcome measures. The outcome measures were the Five Minute Speech S le, the Self-Assessment Manikin and the Controlled Oral Word Association Test. In the oxytocin condition mothers were sadder (p=.01), and they more often initially described their babies as difficult (p=.038), but they reported that the quality of their relationship with their infant was more positive (p=.036). Despite an adequate s le size to answer our central hypothesis, a larger s le may have elucidated a moderating effect of childhood trauma. Oxytocin did not make depressed mothers happier but their perception of the relationship with their baby improved. Treatment with intranasal oxytocin might show some unwanted side-effects in depressed in iduals.
Publisher: Elsevier BV
Date: 03-2023
DOI: 10.1016/J.AJOG.2022.08.036
Abstract: The onset of preterm labor is associated with inflammation. Previous studies suggested that this is distinct from the inflammation observed during term labor. Our previous work on 44 genes differentially expressed in myometria in term labor demonstrated a different pattern of gene expression from that observed in preterm laboring and nonlaboring myometria. We found increased expression of inflammatory genes in preterm labor associated with chorioamnionitis, but in the absence of chorioamnionitis observed no difference in gene expression in preterm myometria regardless of laboring status, suggesting that preterm labor is associated with different myometrial genes or signals originating from outside the myometrium. Given that a small subset of genes were assessed, this study aimed to use RNA sequencing and bioinformatics to assess the myometrial transcriptome during preterm labor in the presence and absence of chorioamnionitis. This study aimed to comprehensively determine protein-coding transcriptomic differences between preterm nonlaboring and preterm laboring myometria with and without chorioamnionitis. Myometria were collected at cesarean delivery from preterm patients not in labor (n=16) and preterm patients in labor with chorioamnionitis (n=8) or without chorioamnionitis (n=6). Extracted RNA from myometrial tissue was prepared and sequenced using Illumina NovaSeq. Gene expression was quantified by mapping the sequence reads to the human reference genome (hg38). Differential gene expression analysis, gene set enrichment analysis, and weighted gene coexpression network analysis were used to comprehensively interrogate transcriptomic differences and their associated biology. Differential gene expression analysis comparing preterm patients in labor with chorioamnionitis with preterm patients not in labor identified 931 differentially expressed genes, whereas comparing preterm patients in labor without chorioamnionitis with preterm patients not in labor identified no statistically significant gene expression changes. In contrast, gene set enrichment analysis and weighted gene coexpression network analysis demonstrated that preterm labor with and without chorioamnionitis was associated with enrichment of pathways involved in activation of the innate immune system and inflammation, and activation of G protein-coupled receptors. Key genes identified included chemotactic CYP4F3, CXCL8, DOCK2, and IRF1 in preterm labor with chorioamnionitis and CYP4F3, FCAR, CHUK, and IL13RA2 in preterm labor without chorioamnionitis. There was marked overlap in the pathways enriched in both preterm labor subtypes. Differential gene expression analysis demonstrated that myometria from preterm patients in labor without chorioamnionitis and preterm patients not in labor were transcriptionally similar, whereas the presence of chorioamnionitis was associated with marked gene changes. In contrast, comprehensive bioinformatic analysis indicated that preterm labor with or without chorioamnionitis was associated with innate immune activation. All causes of preterm labor were associated with activation of the innate immune system, but this was more marked in the presence of chorioamnionitis. These data suggest that anti-inflammatory therapy may be relevant in managing preterm labor of all etiologies.
Publisher: Frontiers Media SA
Date: 10-03-2015
Publisher: IOP Publishing
Date: 29-07-2019
Abstract: The development of polymer-based nanoparticulate delivery systems for siRNA is important for the clinical success of gene therapy. However, there are some major drawbacks that need to be overcome. Short interfering RNA (siRNA) has been investigated as a potential therapeutic drug to silence disease-associated genes, but its usage is limited due to the lack of effective and safe nanocarriers. In this study, DOPE-PEI, a nanoparticle consisting of the fusogenic lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) conjugated with low-molecular-weight, 600 Da, branched polyethylenimine (PEI) was produced and optimized for siRNA delivery. This delivery system was modified with other components such as 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)2000] (DOPE-PEG2K), DOPE-PEG3.4K-bombesin and 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine/1,2-dioleoyl-3-trimethylammonium-propane (DOPE/DOTAP) and tested on PC-3 cells. The conjugation of DOPE to PEI polymer (DOPE-PEI) improved the efficiency of PEI to deliver siRNA into the cytosol and knockdown genes, but demonstrated high toxicity. The addition of DOPE-PEG2K reduced cellular toxicity by masking the surface positive charge of the DOPE-PEI/siRNA complex, with the incorporation of a gastrin-releasing peptide receptor (GRPR) targeting peptide and DOPE/DOTAP components improving the cellular uptake of siRNA into targeted cells and the siRNA knockdown efficiency.
Publisher: Springer Science and Business Media LLC
Date: 10-02-2023
DOI: 10.1007/S43032-023-01183-2
Abstract: The mechanism by which human labor is initiated in the presence of elevated circulating progesterone levels remains unknown. Recent evidence indicates that the progesterone-metabolizing enzyme, 20α-hydroxysteroid dehydrogenase (20α-HSD), encoded by the gene AKR1C1 , may contribute to functional progesterone withdrawal. We found that AKR1C1 expression significantly increased with labor onset in term myometrium, but not in preterm myometrium. Among preterm laboring deliveries, clinically diagnosed chorioamnionitis was associated with significantly elevated AKR1C1 expression. AKR1C1 expression positively correlated with BMI before labor and negatively correlated with BMI during labor. Analysis by fetal sex showed that AKR1C1 expression was significantly higher in women who delivered male babies compared to women who delivered female babies at term, but not preterm. Further, in pregnancies where the fetus was female, AKR1C1 expression positively correlated with the mother’s age and BMI at the time of delivery. In conclusion, the increase in myometrial AKR1C1 expression with term labor is consistent with 20α-HSD playing a role in local progesterone metabolism to promote birth. Interestingly, this role appears to be specific to term pregnancies where the fetus is male. Upregulated AKR1C1 expression in the myometrium at preterm in-labor with clinical chorioamnionitis suggests that increased 20α-HSD activity is a mechanism through which inflammation drives progesterone withdrawal in preterm labor. The link between AKR1C1 expression and maternal BMI may provide insight into why maternal obesity is often associated with dysfunctional labor. Higher myometrial AKR1C1 expression in male pregnancies may indicate fetal sex-related differences in the mechanisms that precipitate labor onset at term.
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.PREGHY.2018.04.009
Abstract: The intrarenal renin-angiotensin system (iRAS) is implicated in the pathogenesis of hypertension, chronic kidney disease and diabetic nephropathy. Urinary angiotensinogen (uAGT) levels reflect the activity of the iRAS and are altered in women with preecl sia. Since Indigenous Australians suffer high rates and early onset of renal disease, we hypothesised that Indigenous Australian pregnant women, like non-Indigenous women with pregnancy complications, would have altered uAGT levels. The excretion of RAS proteins was measured in non-Indigenous and Indigenous Australian women with uncomplicated or complicated pregnancies (preecl sia, diabetes/gestational diabetes, proteinuria/albuminuria, hypertension, small/large for gestational age, preterm birth), and in non-pregnant non-Indigenous women. Non-Indigenous pregnant women with uncomplicated pregnancies, had higher uAGT/creatinine levels than non-Indigenous non-pregnant women (P < 0.01), and levels increased as pregnancy progressed (P < 0.001). In non-Indigenous pregnant women with pregnancy complications, uAGT/creatinine was suppressed in the third trimester (P < 0.01). In Indigenous pregnant women with uncomplicated pregnancies, there was no change in uAGT/creatinine with gestational age and uAGT/creatinine was lower in the 2nd and 3rd trimesters than in non-Indigenous pregnant women with uncomplicated pregnancies (P < 0.03, P < 0.007, respectively). The uAGT/creatinine ratios of Indigenous women with uncomplicated or complicated pregnancies were the same. A decrease in uAGT/creatinine with advancing gestational age was associated with increased urinary albumin/creatinine, as is seen in preecl sia, but it was not specific for this disorder. The reduced uAGT/creatinine in Indigenous pregnant women may reflect subclinical renal dysfunction which limits the ability of the kidney to maintain sodium balance and could indicate an increased risk of pregnancy complications and/or future renal disease.
Publisher: Elsevier
Date: 2015
Publisher: Informa UK Limited
Date: 1998
DOI: 10.3109/07435809809032707
Abstract: The rapid growth of the human fetal adrenal gland, which is primarily a reflection of the growth of the unique fetal zone, is regulated by ACTH acting indirectly to stimulate the expression of locally produced growth factors, of which IGF-II and bFGF appear to play key roles. Through most of gestation, the outer definitive zone appears to function as a reservoir of progenitor cells which move centripetally to populate the rest of the gland. At the end of pregnancy, the fetal zone undergoes senescence through an apoptotic process. Activin and TGF-beta are capable of inducing apoptosis in the fetal zone. Corticotropin-releasing hormone, which is produced by the placenta in markedly increased amounts at the end of gestation, may orchestrate a variety of processes, including direct stimulation of fetal adrenal steroidogenesis, culminating in the initiation of parturition.
Location: Australia
Location: Australia
Location: United Kingdom of Great Britain and Northern Ireland
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Funder: National Health and Medical Research Council
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