ORCID Profile
0000-0002-3834-359X
Current Organisation
The University of Auckland
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Wiley
Date: 16-07-2003
DOI: 10.1046/J.0004-8666.2003.00085.X
Abstract: With the Human Genome Project complete, and microarray technology progressing rapidly, the study of whole genomes has become a reality. The emerging field of genomics is full of promise, has become a cornerstone of commercial drug development, and looks certain to make a major contribution to clinical practice in the future. There is an increasing number of genomic studies concerned with obstetric and gynaecological conditions. Despite this, clinicians in their busy practices often lack a basic understanding of genomics and the tools involved in generating genome-based information. In the present review, we aim to provide the clinician with a basic overview of genomics--what it is, what tools it uses, and how it may benefit our patients. The existing published reports on genomic studies in the reproductive field is reviewed.
Publisher: Informa UK Limited
Date: 10-2015
DOI: 10.2147/JIR.S88039
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 04-2019
Publisher: Oxford University Press (OUP)
Date: 05-09-2006
Abstract: Annexin IV (ANXA4) belongs to a ubiquitous family of Ca(2+)-dependent phospholipid-binding proteins. ANXA4 has been shown to be involved in a range of physiological functions including ion channel regulation, exocytosis and Ca(2+)-dependent signal transduction. The aims of this study were to fully characterize ANXA4 mRNA and protein in human endometrium during the menstrual cycle and to investigate the hormonal regulation of ANXA4. ANXA4 mRNA expression was quantified by real-time PCR in fresh endometrial tissue from cycling women, and protein expression was analysed by immunohistochemistry and western blotting. Hormonal regulation of ANXA4 transcription and translation was investigated using an endometrial explant system. ANXA4 mRNA was significantly up-regulated during mid-secretory (MS) and late-secretory (LS) phases compared with proliferative phases during the menstrual cycle. ANXA4 protein was localized to glandular and luminal epithelium and was present in high levels throughout the menstrual cycle except during early-secretory (ES) phase, when it was significantly reduced. Our data also show that, in proliferative explants, progesterone significantly increased the ANXA4 mRNA and protein after 48h in culture. Estrogen did not have any significant effects. This is the first study to show that ANXA4 transcription and translation are regulated by progesterone and suggests that ANXA4 may be important in regulating ion and water transport across the endometrial epithelium.
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.PLACENTA.2013.04.004
Abstract: Cytokine expression by the placenta is known to change across pregnancy, and is altered in a number of pathologies however the precise mechanisms of cytokine regulation in gestational tissues are not well understood. It has been previously reported that cytokine protein production in gestational tissues is regulated in a tissue-specific manner and appears to be epigenetically regulated. In this study we investigated changes in cytokine mRNA expression and protein production by term placental explants maintained at 8% O2 in the presence or absence of lipopolysaccharide (LPS) (5 μg/mL) and the histone deacetylase inhibitor trichostatin A (TSA) (300 nM). As expected, exposure to LPS stimulated gene expression and protein production of the proinflammatory cytokines IL-1β, IL-6, IL-8 and TNFα, as well as the anti-inflammatory cytokine IL-10. While TSA alone had little effect, TSA co-treatment mitigated the effects of LPS on TNFα and IL-10 protein production with an accompanying reduction in TNFα mRNA transcript levels detected. However, TSA had no significant effect on LPS induced IL-1β, IL-1ra, IL-6 or IL-8 mRNA expression or protein production. The data from this study show that TSA selectively mitigates the stimulatory effect of LPS on TNFα mRNA expression, TNFα protein production and IL-10 protein production. As there is no compensatory effect on IL-1β, IL-1ra, IL-6, or IL-8 mRNA expression or protein production, this results in a dysregulation of the cytokine balance. Insights into HDAC regulation of cytokine expression may provide novel therapeutic strategies for conditions associated with dysregulation of the cytokine network, such as preecl sia and infection mediated preterm labor.
Publisher: Oxford University Press (OUP)
Date: 10-01-2012
Abstract: Progesterone, estrogen and cyclic adenosine monophosphate (cAMP) together regulate the decidualization of human endometrial stromal cells in a time-dependent manner. The role of DNA methylation and the three active DNA methyltransferases (DNMTs) in the regulation of decidualization is gaining interest but the exact role of this epigenetic mechanism during decidualization is largely unknown. We aimed to understand the effect of the main regulators of decidualization on the expression of the DNMTs and in turn on the expression of steroid hormone receptors during the decidualization. We conducted a time-course analysis from 6 h to 10 days to examine the change in gene expression of the DNMTs and the steroid hormone receptors over time in response to estradiol, medroxy-progesterone acetate (MPA) and dibutyryl-cAMP (db-cAMP) in a human endometrial stromal cells (HESC) cell line. Only the combination treatment with MPA-mix (estradiol + MPA + db-cAMP) up-regulated ERα, PGR, progesterone receptor B (PRB) and androgen receptor at 24 h. Both decidualization pathways of db-cAMP and estradiol/MPA, independently and combined, consistently down-regulated DNMT3B mRNA expression from 6 h till 10 days, whereas DNMT1 and DNMT3A mRNA expression were down-regulated transiently. Forced expression of DNMT3B in HESC for 10 days attenuated IGFBP1 mRNA and protein expression and forced expression of DNMT3B combined with MPA-mix treatment synergistically increased the expression of PRB at 24 h. The HESC morphology and proliferation remained unchanged in response to forced expression of DNMT3B. In conclusion, mRNA expression of the DNMTs during decidualization is dynamic, so that expression varies according to the cAMP or estradiol/MPA pathway treatments that regulate them in a time-dependent manner. Although forced expression of DNMT3B by itself is insufficient to inhibit decidualization, forced expression of DNMT3B in combination with MPA-mix synergistically up-regulated PRB, as well as attenuated the expression of IGFBP1, the decidualization marker.
Publisher: American Physiological Society
Date: 04-2010
DOI: 10.1152/AJPENDO.00673.2009
Abstract: Maternal undernutrition during gestation is known to be detrimental to fetal development, leading to a propensity for metabolic disorders later in the adult lives of the offspring. Identifying possible mediators and physiological processes involved in modulating nutrient transport within the placenta is essential to prevent and/or develop treatments for the effects of aberrant nutrition, nutrient transfer, and detrimental changes to fetal development. A potential role for myostatin as a mediator of nutrient uptake and transport from the mother to the fetus was shown through the recent finding that myostatin acts within the human placenta to modulate glucose uptake and therefore homeostasis. The mRNA and protein expression of myostatin and its inhibitor, follistatin-like-3 (FSTL3), was studied in the placenta and skeletal muscle of a transgenerational Wistar rat model of gestational maternal undernutrition in which the F2 offspring postweaning consumed a high-fat (HF) diet. Alterations in placental characteristics and offspring phenotype, specifically glucose homeostasis, were evident in the transgenerationally undernourished (UNAD) group. Myostatin and FSTL3 protein expression were also higher ( P 0.05) in the placentae of the UNAD compared with the control group. At maturity, UNAD HF-fed animals had higher ( P 0.05) skeletal muscle expression of FSTL3 than control animals. In summary, maternal undernutrition during gestation results in the aberrant regulation of myostatin and FSTL3 in the placenta and skeletal muscle of subsequent generations. Myostatin, through the disruption of maternal nutrient supply to the fetus, may thus be a potential mediator of offspring phenotype.
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: American Physiological Society
Date: 02-2008
DOI: 10.1152/AJPENDO.00495.2007
Abstract: Endocannabinoids have been implicated in the mechanisms of implantation, maintenance of pregnancy, and parturition in women. Intrauterine prostaglandin production and actions are also critical in each of these mechanisms. Hence, we have evaluated the effects of cannabinoids on prostaglandin biosynthesis by human gestational membranes. Explants of term amnion and choriodecidua were established and treated with the endogenous endocannabinoids 2-arachidonoyl glycerol and anandamide, as well as the synthetic cannabinoid CP55,940, to determine their ability to modulate PGE 2 production. The explants were also treated with CP55,940 in the presence of either SR141716A (a potent and selective antagonist of the cannabinoid receptor CB1) or NS398 [a cyclooxygenase (COX)-2 inhibitor] to determine whether any observed stimulation of PGE 2 production was mediated through the CB1-receptor and/or COX-2 activity. All three cannabinoids caused a significant increase in PGE 2 production in the amnion but not in the choriodecidua. However, separated fetal (chorion) explants responded to cannabinoid treatment in a similar manner to amnion, whereas maternal (decidual) explants did not. The enhanced PGE 2 production caused by CP55,940 was abrogated by cotreatment with either SR141716A or NS398, illustrating that the cannabinoid action on prostaglandin production in fetal membranes is mediated by CB1 agonism and COX-2. Data from Western blotting show that cannabinoid treatment results in the upregulation of COX-2 expression. This study demonstrates a potential role for endocannabinoids in the modulation of prostaglandin production in late human pregnancy, with potentially important implications for the timing and progression of term and preterm labor and membrane rupture.
Publisher: Oxford University Press (OUP)
Date: 07-09-2010
Abstract: Decidualization, the differentiation of endometrial stromal cells is a crucial step for successful implantation of an embryo, development of the placenta and completion of pregnancy to term. Epigenetic mechanisms are thought to be strongly involved in the regulation of processes controlling implantation, placentation, organ formation and foetal growth. Recent studies suggest that decreased DNA methylation facilitates a receptive endometrium. Hence, the aim of this project was to compare the transcriptional profile changes induced by the inhibitor of DNA methylation, 5-Aza-2'-deoxycytidine (AZA) to the transcriptional changes that happen during decidualization. When DNA methylation was inhibited in a human endometrial stromal cell (HESC) line with AZA, it resulted in the fibroblast-like stromal cells being transformed into decidual-like morphology after 9 days. Expression of both prolactin and insulin-like growth factor binding protein-1, the two established decidualization marker genes, were minimally up-regulated by AZA after 10 days of treatment. In a microarray of a three-way experiment between AZA-treated and oestradiol rogestin/cAMP-treated [medroxy-progesterone acetate (MPA)-mix] HESC and the untreated controls, we detected more than 1000 common genes that had a significant difference of expression compared with the controls. AZA-treated cells in the microarray significantly expressed 76 genes in common with the MPA-mix treated cells, and AZA treatment also differentially regulated 148 genes independently to that of MPA-mix treatment. The MPA-mix regulated at least 36 genes in the cell adhesion, extracellular matrix remodelling and RhoGTPase cytoskeletal reorganization pathway AZA regulated 19 of these genes in common and 15 other RhoGTPase pathway genes. AZA induced some decidualization-like responses of endometrial stromal cells independently of progestins or cAMP, possibly via the cytoskeletal reorganization pathway of the RhoGTPase family.
Publisher: Elsevier BV
Date: 06-2009
DOI: 10.1016/J.CYTOGFR.2009.05.004
Abstract: The establishment of human pregnancy requires the orchestration of substantial cell differentiation and tissue remodelling processes in the context of a complex dialogue between the receptive endometrium and the implanting blastocyst, and is therefore dependent upon a complex sequence of signalling events. Cytokines play an important role in each step of implantation, modulating expression of adhesion molecules on both the fetal and maternal surfaces, regulating expression of the proteases that remodel the extra-cellular matrix, and promoting invasion and differentiation of trophoblasts. Here we review the role of cytokines in regulating the establishment of the fetal-maternal interface, with a particular focus on regulation of the functional expression of CAMs, the ECM and of the proteinases that modulate their function.
Publisher: Elsevier BV
Date: 04-2010
DOI: 10.1016/J.AJOG.2010.01.025
Abstract: The objective of the investigation was to study placental transfer and conjugation of bisphenol A (BPA) across the human placenta. Human placentae obtained from healthy term singleton pregnancies were utilized in a dual recirculating model of ex vivo placental perfusion. Seven placentae were perfused with BPA (10 ng/mL) added to the maternal perfusate for 180 minutes. Antipyrine and fluorescein isothiocyanate dextran were used as positive and negative controls, respectively, to validate integrity of the circuits. Concentrations of BPA and its conjugates were determined by liquid chromatography-mass spectrometry. The transfer percentage for antipyrine and BPA were 25.5 +/- 1.13% and 27.0 +/- 1.88%, respectively, and the transfer index for BPA was 1.1 +/- 0.09 after 180 minutes of perfusion. Only 3.2 +/- 1.6% of BPA in the fetal compartment was in the conjugated form. Bisphenol A at low environmentally relevant levels can transfer across the human placenta, mainly in active unconjugated form.
Publisher: Springer Science and Business Media LLC
Date: 08-2012
Abstract: Differentiation of endometrial stromal cells into decidual cells is crucial for optimal endometrial receptivity. Data from our previous microarray study implied that expression of many cell cycle regulators are changed during decidualization and inhibition of DNA methylation in vitro. In this study, we hypothesized that both the classic progestin treatment and DNA methylation inhibition would inhibit stromal cell proliferation and cell cycle transition. The human endometrial stromal cell line (HESC) was treated from 2 days to 18 days with the DNA methylation inhibitor, 5-aza-2'-deoxycytidine (AZA), a mixture of estradiol rogestin/cyclic adenosine monophosphate ([cAMP] medroxy-progesterone acetate [MPA mix]) or both. Cell growth was measured by cell counting, cell cycle transition and apoptosis were analyzed by flow cytometry, expression of cell cycle regulators were analyzed by quantitative polymerase chain reaction (qPCR) and Western blotting, and change in DNA methylation profiles were detected by methylation-specific PCR. Both AZA and MPA mix inhibited the proliferation of HESC for at least 7 days. Treatment with MPA mix resulted in an early G0/G1 inhibition followed by G2/M phase inhibition at 18 days. In contrast, AZA treatment inhibited cell cycle progression at the G2/M phase throughout. The protein levels of p21(Cip1)and 14-3-3σ were increased with both AZA and MPA mix treatments without any change in the DNA methylation profiles of the genes. Our data imply that the decidualization of HESC is associated with cell cycle arrest at G0/G1 phase initially and G2/M phase at later stages. Our results also suggest that p53 pathway members play a role in the cell cycle regulation of endometrial stromal cells.
Publisher: American Physiological Society
Date: 08-2022
DOI: 10.1152/AJPREGU.00042.2022
Abstract: Fish oil (FO) supplements are consumed during pregnancy to increase dietary omega-3. However, FO is often oxidized past recommended limits. In rats, a large dose of highly oxidized FO substantially increased newborn mortality, but the effects of human-relevant doses of less oxidized oil are unknown. A dose-response study in rats was conducted to estimate the safe level of oxidation during pregnancy. Sprague-Dawley rat dams were mated, then in idually housed and provided with a gel treatment on each day of pregnancy. Treatment groups differed only in the FO content of the gel control (no oil), PV5, PV10, and PV40 [0.05 mL of FO oxidized to a peroxide value (PV) of 5, 10, or 40 meq/kg], or PV40(1 mL) (1 mL of PV40). A subset of dams was culled on gestational day 20 to enable s ling, and the remainder were allowed to give birth. Newborn mortality was recorded. Offspring were s led on postnatal days 2 and 21, and dams on day 21. There were no signs of unwellness during pregnancy. However, there was markedly increased neonatal mortality affecting the PV40(1 mL) (12.8%) and PV40 (6.3%) groups, but not the control, PV5, or PV10 groups (1%–1.4%). Dietary-oxidized FO altered the expression of placental genes involved in antioxidant pathways and the production of free radicals. Highly oxidized FO was toxic in rat pregnancy leading to a marked increase in mortality even at a human-relevant dose. We observed no toxic effects of FOs with PV ≤10 meq/kg, suggesting that this is an appropriate maximum limit.
Publisher: Wiley
Date: 21-12-2008
Abstract: This study reports the discovery and steroid hormonal regulation of a novel glycosylated form of NKp30 in human endometrial epithelium. NKp30 is a member of the immunoglobulin superfamily and one of three existing natural cytotoxicity-triggering receptors. NKp30 is a glycosylated protein and is thought to be selectively expressed in resting and activated natural killer cells. The aims of the present study were to fully characterize NKp30 mRNA and protein in human endometrium during the menstrual cycle, and to investigate the hormonal regulation of NKp30. NKp30 mRNA was significantly up-regulated in fresh tissues during late secretory phase of the menstrual cycle. Interestingly, NKp30 mRNA was also present in clonally derived endometrial epithelial cells (CEE) in comparable amounts to fresh tissue. NKp30 protein was predominantly found in the endometrial glands and luminal epithelia of the secretory phase endometrium. Western blotting and de-glycosylation studies show that a novel glycosylated form of NKp30 is present in endometrial epithelium and that it can dimerize. Further phenotyping of CEE by flow cytometry revealed that they are CK8(+)CD49f(+)NKp30(+)CD45(-)CD56(-). The data also show that transcription and translation of the novel form of NKp30 can be induced by progesterone treatment after 48 h in endometrial explants in vitro. This is the first report to show the presence of both NKp30 mRNA and a novel glycosylated form of NKp30 protein in endometrial epithelial cells.
Publisher: Wiley
Date: 04-2006
Publisher: Oxford University Press (OUP)
Date: 12-2004
Abstract: Endometrium is a dynamic tissue that undergoes cyclic changes each month, under the overall control of estrogen and progesterone. The aims of this study were to investigate the changing global gene expression profile of human endometrium during the menstrual cycle using microarray technology and to determine the correlation between histopathological evaluation and molecular profile of the s les. Standard two-colour cDNA microarrays were performed on the 43 s les against a common reference, using a 10.5 K cDNA glass slide microarray. The results were validated using real-time PCR. Analysis of expression data was carried out using parametric analysis of variance with Benjamini-Hochberg correction. Hierarchical clustering reveals a strong relationship between histopathology and transcriptional profile of the s les. The study identified 1452 genes that showed significant changes in expression (P< or =0.05) across the menstrual cycle, with 425 genes having changes that are at least 2-fold. The data were also independently analysed by a CSIRO algorithm called GeneRaVE that identified a small subset of genes whose expression profiles could be used to classify nearly all the biopsies into their correct cycle stage. We also identified and validated three genes [(natural cytotoxicity triggering receptor (NCR)3, fucosyl transferase (FUT)4 and Fyn-binding protein (FYB)] that had not been shown to have significant cyclic changes in the human endometrium, previously. We have shown for the first time that endometrial cycle stage prediction is possible based on global gene expression profile.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2009
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.1016/J.PLACENTA.2010.03.007
Abstract: To study transplacental transfer and biotransformation of genistein in the human placenta. STUDY DESIGN AND OUTCOMES: Human placentae obtained from healthy term singleton pregnancies were utilised in a dual re-circulating model of ex-vivo placental perfusion. Four placentae were perfused for 180min following addition of genistein (10ng/mL) to the maternal perfusate. Antipyrine and FITC dextran were used as positive and negative controls respectively to validate integrity of the circuits. Concentrations of genistein and its conjugates were determined by liquid chromatography-mass spectrometry (LC-MS). The transfer percentage for antipyrine and genistein was 25.6+/-1.40% and 22.1+/-1.61% respectively and the transfer index for genistein was 0.90+/-0.04 after 180min of perfusion. 12.0+/-2.40% of genistein in the fetal compartment and 7.36+/-4.73% of genistein in the maternal compartment were in the conjugated form. Genistein can transfer across the human placenta at environmentally relevant levels. Placental metabolizing enzymes conjugate a small fraction of genistein into the glucuronide/sulphate form, which is devoid of estrogenic action.
Publisher: Elsevier BV
Date: 10-2006
DOI: 10.1016/J.FERTNSTERT.2006.02.107
Abstract: Mutational screening of the bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) genes in a population with premature ovarian failure (POF) identified no new mutations. However, three single nucleotide polymorphisms in the BMP15 gene, two in the 5' untranslated region (31T>G and 71C>G) and another in exon 1 (387G>A), were found to be common in both POF and control groups.
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.FERTNSTERT.2010.09.030
Abstract: The messenger RNA of the DNA methyltransferases DNMT3a and DNMT3b are expressed temporally in the endometrium across the menstrual cycle, as is the steroid hormone regulation of DNMT1, DNMT3a, and DNMT3b. This suggests that DNA methylation in endometrium is changeable during the menstrual cycle and potentially alters gene expression.
Publisher: Oxford University Press (OUP)
Date: 05-02-2010
Abstract: The endometrium undergoes morphological and functional changes during the menstrual cycle which are essential for uterine receptivity. These changes are driven by estrogen and progesterone and involve the fine control of many different genes-several of which have been identified as being epigenetically regulated. Epigenetic modification may therefore influence the functional changes in the endometrium required for successful implantation. There is, however, only limited information on epigenetic regulation in endometrium. We review the potential role of epigenetic regulation of key processes during the menstrual cycle and present our own findings following a preliminary study into global acetylation levels in the human endometrium. A changing epigenetic state is associated with the differentiation of stem cells into different lineages and thus may be involved in endometrial regeneration. Histone acetylation is implicated in the vascular endothelial growth factor pathway during angiogenesis, and studies using histone deacetylase inhibitors suggest an involvement in endometrial proliferation and differentiation. The processes of decidualization and implantation are also associated with epigenetic change and epigenetic modulators show variable expression across the menstrual cycle. Our own studies found that endometrial global histone acetylation, as determined by western blotting, changed throughout the menstrual cycle and correlated well with expected transcription activity during the different phases. This suggests that epigenetics may be involved in the regulation of endometrial gene expression during the menstrual cycle and that abnormal epigenetic modifications may therefore be associated with implantation failure and early pregnancy loss as well as with other endometrial pathologies.
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/159709
Publisher: Bioscientifica
Date: 07-2008
DOI: 10.1530/REP-07-0548
Abstract: It has been suggested that selectin ligands expressed by the endometrial epithelium are essential for the initial adhesion of the blastocyst to the luminal epithelium of human endometrium. One of the enzymes responsible for the production of selectin ligands is fucosyltransferase 4 (FUT4), a member of α1,3 fucosyltransferases. The aims of the present study were to characterize FUT4 mRNA and protein in human endometrium during the menstrual cycle and to investigate the hormonal regulation of FUT4 whose mRNA expression was quantified by real-time PCR in fresh endometrial tissue from cycling women and protein expression was analyzed by immunohistochemistry and Western blotting. Hormonal regulation of FUT4 transcription was investigated using an endometrial explant system. FUT4 mRNA was significantly upregulated in fresh tissues during early and mid-secretory phases when compared with other phases of the menstrual cycle. FUT4 protein was localized to glandular and luminal epithelium and the expression levels followed the same pattern as for FUT4 mRNA. Our data also show that, in proliferative explants, progesterone significantly increased FUT4 transcription and translation after 24 h in culture. The inductive effect of progesterone on FUT4 transcription was lost after 48 h of treatment. Estrogen did not have any significant effects. These data suggest that the upregulation of selectin ligands in the human endometrium at the time of implantation may be mediated, at least in part, by the regulation of FUT4 expression.
Publisher: Springer Science and Business Media LLC
Date: 20-05-2010
Abstract: The detrimental effects of maternal under-nutrition during gestation on fetal development are well known with an increased propensity of metabolic disorders identified in the adult offspring. Understanding exactly how and by which molecular pathways inadequate nutrition can impact upon offspring phenotype is critical and necessary for the development of treatment methods and ultimately prevention of any negative health effects. Myostatin, a negative regulator of muscle development, has recently been shown to effect glucose homeostasis and fat deposition. The involvement of myostatin in glucose metabolism and adipogenesis thus supports its ability to act in the continued alterations to the postnatal phenotype of the offspring. This hypothesis was examined in the current study using a trans-generational gestationally under-nourished rat model exposed to a high-fat (HF) diet post-weaning. The body weight, body fat, plasma glucose and insulin concentrations of the offspring, both male and female, were investigated in relation to the protein expression of myostatin and its main inhibitor follistatin like-3 (FSTL-3), in skeletal muscle of mature offspring. Sexual dimorphism was clearly evident in the majority of these measures, including myostatin and FSTL-3 expression. Generally males displayed higher ( P 0.05 ) myostatin precursor and dimer expression than females, which was especially apparent ( P 0.01 ) in both chow and HF trans-generationally undernourished (UNAD) groups. In females only, myostatin precursor and dimer expression was altered by both trans-generational under-nutrition and postnatal diet. Overall FSTL-3 expression did not differ between sexes, although difference between sexes within certain treatments and diets were evident. Most notably, HF fed UNAD females had higher (P 0.05) FSTL-3 expression than HF fed UNAD males. The former group also displayed higher (P 0.01) FSTL-3 expression compared to all other female groups. In summary, myostatin may prove to be a key mediator of the effects of inadequate prenatal nutrition, independently or in combination with a high-fat postnatal diet on offspring phenotype. Consequently, further study of myostatin may provide a novel therapeutic pathway for the treatment of metabolic disorders however, it is vital that the influence of nutrition and gender should be taken into consideration.
Publisher: Frontiers Media SA
Date: 02-09-2022
Abstract: In rats, a maternal high-fat diet (HFD) leads to adverse metabolic changes in the adult offspring, similar to the children of mothers with obesity during pregnancy. Supplementation with a high dose of fish oil (FO) to pregnant rats fed a HFD has been shown to prevent the development of insulin resistance in adult offspring. However, the effects of supplementation at a translationally relevant dose remain unknown. To determine whether supplementation with a human-relevant dose of FO to pregnant rats can prevent the long-term adverse metabolic and cardiovascular effects of a maternal HFD on adult offspring. Female rats ( N = 100, 90 days of age) were assigned to HFD (45% kcal from fat) or control diet (CD) for 14 days prior to mating and throughout pregnancy and lactation. Following mating, dams received a gel containing 0.05 ml of FO (human equivalent 2–3 ml) or a control gel on each day of pregnancy. This produced 4 groups, CD with control gel, CD with FO gel, HFD with control gel and HFD with FO gel. Plasma and tissue s les were collected at day 20 of pregnancy and postnatal day 2, 21, and 100. Adult offspring were assessed for insulin sensitivity, blood pressure, DXA scan, and 2D echocardiography. There was an interaction between maternal diet and FO supplementation on insulin sensitivity ( p = 0.005) and cardiac function ( p & 0.01). A maternal HFD resulted in impaired insulin sensitivity in the adult offspring ( p = 0.005 males, p = 0.001 females). FO supplementation in the context of a maternal HFD prevented the reduction in insulin sensitivity in offspring ( p = 0.05 males, p = 0.0001 females). However, in dams consuming CD, FO supplementation led to impaired insulin sensitivity ( p = 0.02 males, p = 0.001 females), greater body weight and reduced cardiac ejection fraction. The effects of a human-relevant dose of maternal FO on offspring outcomes were dependent on the maternal diet, so that FO was beneficial to the offspring if the mother consumed a HFD, but deleterious if the mother consumed a control diet. This study suggests that supplementation with FO should be targeted to women expected to have abnormalities of metabolism such as those with overweight and obesity.
Publisher: Wiley
Date: 26-04-2021
DOI: 10.1002/MRD.23430
Abstract: Cytokines are important regulators of pregnancy and parturition. Aberrant expression of proinflammatory cytokines during pregnancy contributes towards preterm labor, pre‐ecl sia, and gestational diabetes mellitus. The regulation of cytokine expression in human cells is highly complex, involving interactions between environment, transcription factors, and feedback mechanisms. Recent developments in epigenetic research have made tremendous advancements in exploring histone modifications as a key epigenetic regulator of cytokine expression and the effect of their signaling molecules on various organ systems in the human body. Histone acetylation and subsequent deacetylation by histone deacetylases (HDACs) are major epigenetic regulators of protein expression in the human body. The expression of various proinflammatory cytokines, their role in normal and abnormal pregnancy, and their epigenetic regulation via HDACs will be discussed in this review.
Publisher: Elsevier BV
Date: 10-2011
DOI: 10.1016/J.PLACENTA.2011.07.014
Abstract: 4-nonylphenol (4-NP) is an estrogenic endocrine active chemical that is present in detergents and is known to contaminate food and drinking water. The aim of the present study was to evaluate whether 4-NP crosses the human placenta and if so, to what extent. Human placentae obtained from healthy term singleton pregnancies were utilized in a dual ex-vivo re-circulating model of placental perfusion. Six placentae were perfused for 180 min following addition of 4-NP (30 ng/mL) to the maternal perfusate. Antipyrine and FITC dextran were used as positive and negative controls respectively to validate the integrity of the circuits. 4-NP was measured by High Performance Liquid Chromatography coupled with Fluorescence Detection (HPLC-FD). After 180 min of perfusion the transfer percentages for antipyrine and 4-NP were 25.6 ± 1.4% (mean ± s.e.m, n = 6) and 22.75 ± 3.76% respectively and the transfer index for 4-NP was 0.8. We conclude that the intact form of 4-NP at environmentally relevant concentrations can transfer across the human placenta albeit at a slow rate.
No related grants have been discovered for Anna Ponnampalam.