ORCID Profile
0000-0002-9250-2192
Current Organisation
Flinders University
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Physiology | Animal Physiology—Systems | Physiology Not Elsewhere Classified | Cell Development (Incl. Cell Division And Apoptosis) | Genetic Development (Incl. Sex Determination)
ANZSRC Socio-Economic Objective (SEO)
Biological sciences | Clinical health not specific to particular organs, diseases and conditions | Livestock not elsewhere classified | Sheep—meat |
Related Links
Publications
Maternal Insulin-Like Growth Factors-I and -II Act via Different Pathways to Promote Fetal Growth
Publisher: The Endocrine Society
Date: 07-2006
DOI: 10.1210/EN.2005-1328
Abstract: The placenta transports substrates and wastes between the maternal and fetal circulations. In mice, placental IGF-II is essential for normal placental development and function but, in other mammalian species, maternal circulating IGF-II is substantial and may contribute. Maternal circulating IGFs increase in early pregnancy, and early treatment of guinea pigs with either IGF-I or IGF-II increases placental and fetal weights by mid-gestation. We now show that these effects persist to enhance placental development and fetal growth and survival near term. Pregnant guinea pigs were infused with IGF-I, IGF-II (both 1 mg/kg·d), or vehicle sc from d 20–38 of pregnancy and killed on d 62 (term = 69 d). IGF-II, but not IGF-I, increased the mid-sagittal area and volume of placenta devoted to exchange by approximately 30%, the total volume of trophoblast and maternal blood spaces within the placental exchange region (+29% and +46%, respectively), and the total surface area of placenta for exchange by 39%. Both IGFs reduced resorptions, and IGF-II increased the number of viable fetuses by 26%. Both IGFs increased fetal weight by 11–17% and fetal circulating amino acid concentrations. IGF-I, but not IGF-II, reduced maternal adipose depot weights by approximately 30%. In conclusion, increased maternal IGF-II abundance in early pregnancy promotes fetal growth and viability near term by increasing placental structural and functional capacity, whereas IGF-I appears to ert nutrients from the mother to the conceptus. This suggests major and complementary roles in placental and fetal growth for increased circulating IGFs in early to mid-pregnancy.
Early treatment of the pregnant guinea pig with IGFs promotes placental transport and nutrient partitioning near term
Publisher: American Physiological Society
Date: 03-2007
DOI: 10.1152/AJPENDO.00320.2006
Abstract: Appropriate partitioning of nutrients between the mother and conceptus is a major determinant of pregnancy success, with placental transfer playing a key role. Insulin-like growth factors (IGFs) increase in the maternal circulation during early pregnancy and are predictive of fetal and placental growth. We have previously shown in the guinea pig that increasing maternal IGF abundance in early to midpregnancy enhances fetal growth and viability near term. We now show that this treatment promotes placental transport to the fetus, fetal substrate utilization, and nutrient partitioning near term. Pregnant guinea pigs were infused with IGF-I, IGF-II (both 1 mg·kg −1 ·day −1 ) or vehicle subcutaneously from days 20–38 of pregnancy (term = 69 days). Tissue uptake and placental transfer of the nonmetabolizable radio analogs [ 3 H]methyl-d-glucose (MG) and [ 14 C]aminoisobutyric acid (AIB) in vivo was measured on day 62. Early pregnancy exposure to elevated maternal IGF-I increased placental MG uptake by % ( P = 0.004), whereas each IGF increased fetal plasma MG concentrations by 40–50% ( P 0.012). Both IGFs increased fetal tissue MG uptake ( P 0.048), whereas IGF-I also increased AIB uptake by visceral organs ( P = 0.046). In the mother, earlier exposure to either IGF increased AIB uptake by visceral organs ( P 0.014), whereas IGF-I also enhanced uptake of AIB by muscle ( P = 0.044) and MG uptake by visceral organs ( P = 0.016) and muscle ( P = 0.046). In conclusion, exogenous maternal IGFs in early pregnancy sustainedly increase maternal substrate utilization, placental transport of MG to the fetus, and fetal utilization of substrates near term. This was consistent with the previously observed increase in fetal growth and survival following IGF treatment.
Paternal Contribution to Small for Gestational Age Babies: A Multicenter Prospective Study
Publisher: Wiley
Date: 05-2011
DOI: 10.1038/OBY.2010.279
Abstract: Our aims were to investigate whether men who fathered small for gestational age (SGA) infants themselves had lower birthweight, were more likely to be obese, have central adiposity and elevated blood pressure in adult life compared with men who fathered non-SGA infants. A total of 2,002 couples participating in the Screening for Pregnancy Endpoints (SCOPE) study were enrolled in early pregnancy and pregnancy outcome data collected prospectively. SGA was defined as birthweight 102 cm. Logistic regression was used to compare rates of obesity, and central adiposity between men who fathered SGA infants compared with those with non-SGA infants and the final model was adjusted for maternal and paternal confounders. The men who fathered an SGA infant (209 (10.4%)) themselves had lower mean birthweight (3,291 (530) g vs. 3,472 (584) g, P < 0.0001), were more likely to be obese (50 (24.8%) vs. 321 (18.3%), adjusted odds ratio (OR) 1.50, 95% confidence interval 1.05-2.16, adjusted for maternal and paternal factors) and to have central adiposity (52 (25.1%) vs. 341 (19.2%), adjusted OR 1.53, 95% confidence interval 1.06-2.20) compared with men who fathered a non-SGA infant. Elevated paternal blood pressure was not associated with SGA. In conclusion, we report a novel relationship between paternal obesity/central adiposity and birth of an SGA infant, which appears to be independent of maternal factors associated with fetal growth restriction.
Emergency contraception – an evidence‐based practice guide
Publisher: Wiley
Date: 12-2017
DOI: 10.1002/JPPR.1416
Safety and protective effects of maternal influenza vaccination on pregnancy and birth outcomes: A prospective cohort study
Publisher: Elsevier BV
Date: 09-2020
IFPA Meeting 2009 Workshops Report
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.PLACENTA.2009.12.008
Abstract: Workshops are an important part of the annual meeting of the International Federation of Placenta Associations (IFPA). At IFPA Meeting 2009 erse topics were discussed in twelve themed workshops. Topics covered included: immune response to pregnancy signaling between fetus and placenta bioactive lipids in placenta placenta in agricultural species epigenetics and placentation trophoblast deportation glucocorticoids and placental function endothelium placental transport genes and placenta uteroplacental blood flow and placental stem cells. This report is a full summary of the various topics covered.
Variation in ultrastructure of mucoid coat and shell membrane secretion of a dasyurid marsupial
Publisher: CSIRO Publishing
Date: 1996
DOI: 10.1071/RD9960645
Abstract: In the dasyurid marsupial Sminthopsis crassicaudata, the shell membrane of cleaving embryos has a compact granular structure but becomes fibrous around blastocysts. Polyclonal antibodies were raised against the extracellular coats, mucoid and shell membrane, of oocytes and early embryos. Immunogold cytochemistry resulted in labelling of secretory granules in the epithelia of both the ulla and isthmus of the oviduct, although the secretory granules of these two regions differed in their ultrastructural appearance. Those in the ulla were heterogeneous with areas of varying electron density, whereas those in the isthmus were electron dense and homogeneous. Shell membrane precursors were found in secretory granules in the epithelia of the uterotubal junction and endometrial glands and were electron lucent.
Altered placental development in interleukin-10 null mutant mice
Publisher: Elsevier BV
Date: 04-2003
Abstract: Placental morphogenesis and nutrient transfer function are regulated by growth factors at the foeto-maternal interface. Interleukin (IL)-10, expressed in the decidua and placenta, is implicated in regulating extravillous cytotrophoblast invasion through inhibiting matrix metalloproteinase expression and influencing the quality of the maternal immune response. Our laboratory has previously found that IL-10 deficiency in both the mother and foetus increases foetal weight at day 18 without altering placental weight suggesting that the placenta has a greater functional capacity when IL-10 is absent. The present study has used IL-10 null mutant (IL-10-/-) mice to investigate the role of IL-10 in placental development. Placental structure was assessed in adult virgin IL-10-/- or wild-type (IL-10+/+) mice mated with males of the same genotype and sacrificed at day 18 of gestation. Mid-sagittal cross sections of placental tissue were stained with Masson's trichrome or immuno-labelled with MTS-12 and pan-cytokeratin reactive antibodies to identify foetal endothelial cells and trophoblasts, respectively, and examined with video image analysis. IL-10 deficiency increased the total cross sectional area of the placenta by 28 per cent (IL-10-/- n=22 placentae from 8 dams, IL-10+/+n =21 placentae from 9 dams, P=0.026), principally through increasing the cross sectional area of placental labyrinth by 37 per cent (P=0.025). The proportion of maternal blood space in the labyrinth was increased by 26 per cent (P=0.001) and that of trophoblast was decreased by 16 per cent (P=0.001) in IL-10-/- placentae. The surface area of trophoblast per gram of labyrinth was increased by 41 per cent (P=0.0005) in IL-10-/- placentae. In the absence of IL-10, structural correlates of placental function are enhanced consistent with concomitant increases in foetal growth. These data indicate that IL-10 is a regulator of placental morphogenesis, acting to retard expansion of the placental labyrinth and to modify the architecture of the maternal blood sinuses. Since previous studies have paradoxically shown that postnatal growth is impaired in IL-10 null mutants, these observations are consistent with a role for IL-10 in regulating placental development and foetal programming.
Ontogeny of Placental Structural Development and Expression of the Renin-Angiotensin System and 11β-HSD2 Genes in the Rabbit
Publisher: Elsevier BV
Date: 07-2009
DOI: 10.1016/J.PLACENTA.2009.04.006
Abstract: Common pregnancy complications are associated with impaired placental development. This study aimed to characterise the ontogeny of structural correlates of rabbit placental function, its expression of genes encoding components of the renin-angiotensin system (RAS), as well as 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) mRNA since these are known to be expressed by the placenta and are associated with pregnancy complications, including preecl sia and intrauterine programming. Placentae were collected at gestational age (GA) 14, 21 and 28 (term=32 days). Gene expression was analysed using real time PCR and placental structures were quantified via image analyses. The volume densities and volumes of trophoblast, fetal capillaries, maternal blood space, surface density and surface area of trophoblast all progressively increased, while the arithmetic mean barrier thickness of trophoblast decreased across gestation. Maternal plasma renin activity (PRA) was positively correlated with volumes of trophoblast and maternal blood space, surface density and surface area of trophoblast. Placental renin mRNA declined ( downward arrow62% P<0.01) across gestation and was negatively correlated with maternal PRA (GA0), fetal and placental weights, placental angiotensin type 1 and 2 receptors (AT(1)R and AT(2)R) mRNA and volume of trophoblast. AT(1)R mRNA expression was increased by 92% (P<0.001) across gestation. AT2R mRNA expression was approximately 81% (P<0.01) greater at GA14 compared to GA21. Placental 11beta-HSD2 mRNA expression was approximately 74% greater (P<0.01) at GA21 than GA14, but by GA28 was similar to that at GA14. These data show that changes in placental gene expression are associated with key events in placental and fetal development, indicating that the rabbit provides a good model for investigations of pregnancy perturbations that alter the RAS or programme the fetus.
Peripheral maternal haemodynamics across pregnancy in hypertensive disorders of pregnancy
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.PREGHY.2019.02.006
Abstract: Evaluating maternal haemodynamics across pregnancy in uncomplicated pregnancies and those complicated by hypertensive disorders of pregnancy (HDP). Prospective cohort study from 2015 to 2018 of healthy, nulliparous, singleton-bearing women. Maternal haemodynamics assessed by Uscom BP+ at 9-16 and 32-36 weeks' gestation in pregnancies complicated by HDP [preecl sia with severe (sPE n = 12) and without severe clinical features (nsPE n = 49), gestational hypertension (GH n = 25), transient gestational hypertension (TGH n = 33)] were compared to uncomplicated pregnancies (n = 286) using mixed-effects linear modelling. Maternal haemodynamic adaptation in uncomplicated pregnancies and those complicated by HDP. Between the two measurements, haemodynamic adaptation in women with sPE and nsPE was significantly different compared to those with uncomplicated pregnancies. An additional increase was observed for peripheral systolic blood pressure [SBP 14.3 mmHg, 8.6-20.1 (sPE)], peripheral diastolic blood pressure [DBP 7.7 mmHg, 3.3-12.1 (sPE) 2.6 mmHg, 3.3-12.1 (nsPE)] peripheral mean arterial pressure [MAP 10.6 mmHg, 5.8-15.5 (sPE) 3.4 mmHg, 0.8-6.0 (nsPE)], peripheral pulse pressure [PP 6.6 mmHg, 2.1-11.1 (sPE)], central SBP [15.8 mmHg, 10.4-21.2 (sPE) 2.9 mmHg, 0.1-5.8 (nsPE)], central DBP [8.3 mmHg, 3.9-12.6 (sPE) 2.5 mmHg, 0.2-4.8 (nsPE), central MAP [10.8 mmHg, 6.4-15.2 (sPE) 2.6 mmHg, 0.3-5.0 (nsPE)] and central PP [7.6 mmHg, 3.9-11.3 (sPE)]. Augmentation index (AIx) decreased less (15.5%, 6.3-24.6 (sPE) 9.0%, 4.2-13.6 (nsPE)] compared to uncomplicated pregnancies. Haemodynamic adaptation across pregnancy in women with GH and TGH was not different from those with uncomplicated pregnancies. Women who develop preecl sia show an altered, while those who develop GH or TGH demonstrate a comparable haemodynamic adaptation compared to uncomplicated pregnancies. TGH is not a benign condition.
Haemolysis detection in microRNA-seq from clinical plasma samples
Publisher: Cold Spring Harbor Laboratory
Date: 04-04-2022
DOI: 10.1101/2022.03.27.22273016
Abstract: The abundance of cell-free microRNA (miRNA) has been measured in many body fluids, including blood plasma, which has been proposed as a source with novel, minimally invasive biomarker potential for several diseases. Despite improvements in quantification methods for plasma miRNAs, there is no consensus on optimal reference miRNAs or to what extent haemolysis may affect plasma miRNA content. Here we propose a new method for the detection of haemolysis in miRNA high-throughput sequencing (HTS) data from libraries prepared using human plasma. To establish a miRNA haemolysis signature in plasma we first identified differentially expressed miRNAs between s les with known haemolysis status and selected miRNA with statistically significant higher abundance in our haemolysed group. Given there may be both technical and biological reasons for differential abundance of signature miRNA, and to ensure the method developed here was relevant outside of our specific context, that is women of reproductive age, we tested for significant differences between pregnant and non-pregnant groups. Here we report a novel 20 miRNA signature (miR-106b-3p, miR-140-3p, miR-142-5p, miR-532-5p, miR-17-5p, miR-19b-3p, miR-30c-5p, miR-324-5p, miR-192-5p, miR-660-5p, miR-186-5p, miR-425-5p, miR-25-3p, miR-363-3p, miR-183-5p, miR-451a, miR-182-5p, miR-191-5p, miR-194-5p, miR-20b-5p) that can be used to identify the presence of haemolysis, in silico , in high throughput miRNA sequencing data. Given the potential for haemolysis contamination, we recommend that assay for haemolysis detection become standard pre-analytical practice and provide here a simple method for haemolysis detection.
Mechanisms linking exposure to preeclampsia in utero and the risk for cardiovascular disease
Publisher: Cambridge University Press (CUP)
Date: 19-02-2020
DOI: 10.1017/S2040174420000094
Abstract: Preecl sia (PE) is now recognised as a cardiovascular risk factor for women. Emerging evidence suggests that children exposed to PE in utero may also be at increased risk of cardiovascular disease (CVD) in later life. In iduals exposed to PE in utero have higher systolic and diastolic blood pressure and higher body mass index (BMI) compared to those not exposed to PE in utero . The aim of this review is to discuss the potential mechanisms driving the relationship between PE and offspring CVD. Exposure to an adverse intrauterine environment as a consequence of the pathophysiological changes that occur during a pregnancy complicated by PE is proposed as one mechanism that programs the fetus for future CVD risk. Consistent with this hypothesis, animal models of PE where progeny have been studied demonstrate causality for programming of offspring cardiovascular health by the preecl tic environment. Shared alleles between mother and offspring, and shared lifestyle factors between mother and offspring provide alternate pathways explaining associations between PE and offspring CVD risk. In addition, adverse lifestyle habits can also act as second hits for those programmed for increased CVD risk. PE and CVD are both multifactorial diseases and, hence, identifying the relative contribution of PE to offspring risk for CVD is a very complex task. However, considering the emerging strong association between PE and CVD, those exposed to PE in utero may benefit from targeted primary CVD preventive strategies.
Fetal leptin is a signal of fat mass independent of maternal nutrition in ewes fed at or above maintenance energy requirements
Publisher: Oxford University Press (OUP)
Date: 08-2002
DOI: 10.1095/BIOLREPROD67.2.493
Abstract: In adults, circulating leptin concentrations are dependent on body fat content and on current nutritional status. However, the relationships among maternal nutrient intake, fetal adiposity, and circulating leptin concentrations before birth are unknown. We investigated the effects of an increase in nutrient intake in the pregnant ewe on fetal adiposity and plasma leptin concentrations during late gestation. Between 115 and 139-141 days gestation (term = 147 +/- 3 days gestation), ewes were fed a diet calculated to provide either maintenance (control, n = 6) or approximately 155% of maintenance requirements (well-fed, n = 8). The fetal fat depots (perirenal and interscapular) were dissected, and the relative proportion of unilocular and multilocular adipocytes in each depot was determined. Maternal plasma glucose and leptin concentrations were significantly increased in well-fed ewes. Fetal plasma glucose concentrations were also higher in the well-fed group (115-139 days gestation: control, 1.65 +/- 0.14 mmol/L well-fed, 2.00 +/- 0.14 mmol/L F = 5.76, P < 0.04). There was no effect of increasing maternal feed intake on total fat mass, the relative mass of unilocular fat, or fetal plasma leptin concentrations (115-139 days gestation: control, 5.2 +/- 0.8 ng/ml well-fed, 4.7 +/- 0.7 ng/ml). However, in both the control and well-fed groups fetal plasma leptin concentrations (y) were positively correlated with the relative mass of unilocular fat (x): y = 1.51x + 1.70 (R = 0.76, P < 0.01). Thus, fetal leptin may play a role as a signal of unilocular fat mass in the fetus when maternal nutrient intake is at or above maintenance requirements.
DraculR: A Web-Based Application for In Silico Haemolysis Detection in High-Throughput microRNA Sequencing Data
Publisher: MDPI AG
Date: 09-02-2023
Abstract: The search for novel microRNA (miRNA) biomarkers in plasma is h ered by haemolysis, the lysis and subsequent release of red blood cell contents, including miRNAs, into surrounding fluid. The biomarker potential of miRNAs comes in part from their multicompartment origin and the long-lived nature of miRNA transcripts in plasma, giving researchers a functional window for tissues that are otherwise difficult or disadvantageous to s le. The inclusion of red-blood-cell-derived miRNA transcripts in downstream analysis introduces a source of error that is difficult to identify posthoc and may lead to spurious results. Where access to a physical specimen is not possible, our tool will provide an in silico approach to haemolysis prediction. We present DraculR, an interactive Shiny/R application that enables a user to upload miRNA expression data from a short-read sequencing of human plasma as a raw read counts table and interactively calculate a metric that indicates the degree of haemolysis contamination. The code, DraculR web tool and its tutorial are freely available as detailed herein.
Distinct actions of insulin-like growth factors (IGFs) on placental development and fetal growth.
Publisher: Elsevier BV
Date: 03-2008
DOI: 10.1016/J.PLACENTA.2007.12.002
Abstract: Placental insufficiency is thought to be a key factor in many cases of intrauterine growth restriction which complicates about 6% of pregnancies in western countries. Understanding the molecular control of placental and fetal growth is essential to identifying diagnostic and therapeutic targets to improve pregnancy success. Insulin-like growth factor (IGF)-I and IGF-II gene ablation or maternal food restriction reduce tissue and circulating IGF abundance in the fetus, placenta and mother and are associated with both placental and fetal growth restriction. Conversely, in vivo treatment of the pregnant guinea pig with IGF-I or IGF-II from early to mid pregnancy increases fetal weight and enhances placental transport near term. IGF-II, and an IGF2R specific analogue, enhanced placental structural differentiation, whereas IGF-I altered maternal body composition. These outcomes demonstrate endocrine roles within the mother for both IGFs, as well as autocrine aracrine effects of IGF-II in enhancing placentation and pregnancy success. Therefore, factors that alter placental expression of IGF-II, or maternal circulating IGF-I or IGF-II in early pregnancy may affect placental exchange function late in gestation when the demands of the fetus escalate. IGF-II within the fetus may also signal its nutrient demands to the placenta to improve its function to suit. Therefore each IGF of endocrine and local origin has important, but distinct, roles in placental development and function.
DraculR: A web based application for in silico haemolysis detection in high throughput small RNA sequencing data
Publisher: Cold Spring Harbor Laboratory
Date: 31-03-2022
DOI: 10.1101/2022.03.27.22273019
Abstract: The search for novel microRNA (miRNA) biomarkers in plasma is h ered by haemolysis, the lysis and subsequent release of red blood cell (RBC) contents, including miRNAs, into surrounding fluid. The biomarker potential of miRNAs comes in part from their multi-compartment origin, and the long-lived nature of miRNA transcripts in plasma, giving researchers a functional window for tissues that are otherwise difficult or disadvantageous to s le. The inclusion of RBC derived miRNA transcripts in downstream analysis introduces a source of error that is difficult to identify post hoc and may lead to spurious results. Where access to a physical specimen is not possible, our tool will provide an in silico approach to haemolysis prediction. We present DraculR, an interactive Shiny/R application that enables a user to upload microRNA expression data from short read sequencing of human plasma as a raw read counts table and interactively calculate a metric that indicates the degree of haemolysis contamination. DraculR and its tutorial are freely available from ( mxhp75.shinyapps.io/shinyV / ). Code is available from ( xhp75/shinyV .git ).
Hypertensive disorders of pregnancy and later cardiovascular disease risk in mothers and children
Publisher: Cambridge University Press (CUP)
Date: 15-10-2021
DOI: 10.1017/S2040174420000896
Abstract: Preecl sia (PE) and gestational hypertension (GH) are pregnancy-specific diseases that occur in around 10% of pregnancies worldwide. Increasing evidence suggests that women whose pregnancies were complicated by PE or GH, and their offspring, are at increased risk of cardiovascular disease (CVD) later in life. We hypothesised that PE and GH would associate with CVD risk factors 8–10 years after the first pregnancy in the mother and child and that differences in cardiovascular risk profile would be seen between 8- and 10-year-old male and female children. This is a follow-up study of the Adelaide SCOPE pregnancy cohort where 1164 nulliparous women and their babies were recruited between 2005 and 2008. Haemodynamic function was assessed using non-invasive USCOMBP+ and USCOM1A devices. Microvascular function was assessed by post-occlusive reactive hyperaemia. Of the 273 mother–child pairs followed up, 38 women had PE and 20 had GH during pregnancy. Augmentation index (Aix) and suprasystolic pulse pressure (ssPP) were increased, whereas measures of microvascular function were decreased in children who were born to PE compared to uncomplicated pregnancies. Female children had decreased Aix and ssPP compared to male children after in utero exposure to PE. Women who developed GH during their first pregnancy had increased systolic, diastolic and mean arterial pressures compared to women who had uncomplicated pregnancy. Our data suggest that GH is associated with increased cardiovascular risk in women 8–10 years after first pregnancy and PE is associated with increased offspring risk at 8–10 years of age, highlighting differences between these two hypertensive disorders of pregnancy.
The obesity associated FTO gene variant and the risk of adverse pregnancy outcomes: Evidence from the SCOPE study
Publisher: Wiley
Date: 21-10-2016
DOI: 10.1002/OBY.21662
Abstract: To investigate whether the FTO rs9939609 single nucleotide polymorphism (SNP), which is a risk factor for obesity and vascular diseases, is also associated with pregnancy complications including pre-ecl sia, gestational hypertension, small for gestational age pregnancy (SGA), and spontaneous preterm birth (sPTB). A case-control study of 1,741 nulliparous Caucasian women, their partners, and infants was conducted. DNA was extracted from peripheral blood or saliva from parents and cord blood from infants and genotyped using the Sequenom MassARRAY system. The prevalence of maternal and infant AA genotype of FTO rs9939609 was increased in the SGA group compared with the uncomplicated pregnancy group (19.2% vs. 13.4%, OR = 1.7, 95% CI = 1.1-2.6, P = 0.02 and 24.6% vs. 12.5%, OR = 2.7, 95% CI = 1.6-4.6, P = 0.0002). The prevalence of maternal and infant AA genotype of FTO rs9939609 was also increased in the sPTB group compared with the uncomplicated pregnancy group (20.8% vs. 13.4%, OR = 2.1, 95% CI = 1.2-3.8, P = 0.009 and 20.0% vs. 12.5%, OR = 2.4, 95% CI = 1.0-5.3, P = 0.03). The maternal and infant AA genotype of the obesity associated FTO rs9939609 SNP associates with increased risk for SGA and sPTB. This SNP may be important in predicting the risk of these pregnancy complications and subsequent vascular diseases.
Chronic maternal hypertension affects placental gene expression and differentiation in rabbits
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2010
DOI: 10.1097/HJH.0B013E3283369F1E
Abstract: Previously, we have shown that adult offspring from hypertensive rabbits develop hypertension. We aimed to determine the effects of mild (+15 mmHg) and moderate (+25 mmHg) increases in maternal blood pressure and plasma renin activity on placental differentiation and expression of components of the renin-angiotensin system and 11[beta]-hydroxysteroid dehydrogenase type 2 mRNA in rabbits. Placentas were collected from normotensive (sham), mild (2-kidney-1-cellophane wrapped 2K-1W) and moderate (2-kidney-2-cellophane wrapped 2K-2W) hypertensive groups at gestational age of 14, 21 and 28 days. Placental gene expression was quantified by reverse transcriptase-PCR, and morphometry was assessed by videoimage analyses of placental sections. Fetal weight was similar between groups across gestation. In the 2K-1W group at gestational age day 14, fetal-to-placental weight ratio was increased (approximately 34%) as were volumes of fetal capillaries ([up arrow]56%) and maternal blood space at gestational age day 21 ([up arrow]55%) compared with sham (all P < 0.05). In the 2K-2W group, fetal-to-placental weight ratio was increased at gestational age day 21 (approximately 25% P < 0.01) with an accompanying reduction in placental weight, and at gestational age day 28, volume density of fetal capillaries was increased (approximately 22% P < 0.05). Placental renin mRNA was lower in both the 2K-1W (approximately 88%) and 2K-2W (approximately 98%) groups at gestational age day 28 (all P < 0.01). Placental 11[beta]-hydroxysteroid dehydrogenase type 2 mRNA was lower in the 2K-1W (approximately 36%) and 2K-2W (approximately 31%) groups at gestational age day 14 and greater (approximately 36%) in the 2K-2W group at gestational age day 21 (all P < 0.01). Associations between placental AT1R and AT2R mRNA and placental differentiation were disturbed by hypertension. Mild and moderate maternal hypertension differentially alters placental structure and gene expression that may affect placental functional capacity and contribute to programming of hypertension in offspring.
Pregnancy complications and cardiovascular disease risk perception: A qualitative study
Publisher: Public Library of Science (PLoS)
Date: 21-07-2022
DOI: 10.1371/JOURNAL.PONE.0271722
Abstract: We aimed to assess women’s perceptions on the long-term risks for cardiovascular disease (CVD) after major pregnancy complications. Women who experienced major pregnancy complications and those who experienced uncomplicated pregnancies were invited to participate in a qualitative study. Focus group discussions (FGDs) and self-administered questionnaires were used to explore: The knowledge of long-term sequelae after experiencing a major pregnancy complication Importance of education on heart health The practicality of referral to a clinic after pregnancy complications Willingness for regular postpartum clinic visits after pregnancy complications. A thematic qualitative analysis was undertaken. 26 women participated in four FGDs. The majority of women did not know of the association between major pregnancy complications and CVD. The main views expressed were: Women who experience pregnancy complications should receive education on improving heart health An appointment for the first CVD risk screening visit needs to be made prior to discharge from the delivery suite Women will benefit by having the option to select between a hospital and a general-practitioner based model of follow up. These views are important in developing postpartum strategies to reduce CVD risk among women who experience pregnancy complications.
A Label-free Selected Reaction Monitoring Workflow Identifies a Subset of Pregnancy Specific Glycoproteins as Potential Predictive Markers of Early-onset Pre-eclampsia
Publisher: Elsevier BV
Date: 11-2013
The interaction between the maternal BMI and angiogenic gene polymorphisms associates with the risk of spontaneous preterm birth
Publisher: Oxford University Press (OUP)
Date: 04-04-2012
Abstract: Obesity is associated with an increased level of inflammation. Interactions between inflammatory and angiogenic pathways are implicated in the major pregnancy disorders. The aim of this study was to investigate whether functional polymorphisms in angiogenesis-regulating genes (VEGFA rs699947, VEGFA rs3025039, KDR rs2071559 and ANGPT1 rs2507800) interact with the maternal BMI to modify the risk of a spontaneous preterm birth (sPTB). We conducted a nested case-control study of 1190 nulliparous Caucasian women (107 sPTBs and 1083 controls). Spontaneous PTB was defined as spontaneous preterm labour or a preterm premature rupture of membranes resulting in a preterm birth at <37 weeks of gestation. DNA was extracted from the peripheral blood and genotyped using the Sequenom MassARRAY system. Among overweight or obese women (BMI ≥25), the VEGFA rs699947 AA genotype was associated with a higher risk of sPTBs [odds ratio (OR) = 2.4, 95% confidence interval (CI): 1.4-4.6, P = 0.001] and a significant interaction between the BMI and the polymorphism was detected (OR = 4.2, 95% CI: 1.7-10.9, P = 0.003). Among women with a BMI <25, ANGPT1 rs2507800 AA genotype was associated with a higher risk of sPTB (OR = 2.3, 95% CI: 1.2-4.4, P= 0.02) and a significant interaction between BMI and the polymorphism was detected (OR = 3.3, 95% CI: 1.1-9.3, P = 0.02). All results remained significant after adjusting for potential confounding factors. The maternal BMI interacts with angiogenesis-regulating gene polymorphisms to modify the risk of sPTBs.
Recent progress towards understanding the role of DNA methylation in human placental development
Publisher: Bioscientifica
Date: 07-2016
DOI: 10.1530/REP-16-0014
Abstract: Epigenetic modifications, and particularly DNA methylation, have been studied in many tissues, both healthy and diseased, and across numerous developmental stages. The placenta is the only organ that has a transient life of 9 months and undergoes rapid growth and dynamic structural and functional changes across gestation. Additionally, the placenta is unique because although developing within the mother, its genome is identical to that of the foetus. Given these distinctive characteristics, it is not surprising that the epigenetic landscape affecting placental gene expression may be different to that in other healthy tissues. However, the role of epigenetic modifications, and particularly DNA methylation, in placental development remains largely unknown. Of particular interest is the fact that the placenta is the most hypomethylated human tissue and is characterized by the presence of large partially methylated domains (PMDs) containing silenced genes. Moreover, how and why the placenta is hypomethylated and what role DNA methylation plays in regulating placental gene expression across gestation are poorly understood. We review genome-wide DNA methylation studies in the human placenta and highlight that the different cell types that make up the placenta have very different DNA methylation profiles. Summarizing studies on DNA methylation in the placenta and its relationship with pregnancy complications are difficult due to the limited number of studies available for comparison. To understand the key steps in placental development and hence what may be perturbed in pregnancy complications requires large-scale genome-wide DNA methylation studies coupled with transcriptome analyses.
The growth hormone–insulin-like growth factor axis in pregnancy
Publisher: Bioscientifica
Date: 12-2021
DOI: 10.1530/JOE-21-0087
Abstract: The growth hormone (GH)–insulin-like growth factor (IGF) axis is one of the main drivers of mammalian growth and development. Pituitary secretion of GH is pulsatile and under positive and negative hypothalamic control, as well as stimulation from gastric-secreted acyl-ghrelin. GH acts both directly via the GH-receptor (GHR) and indirectly via stimulation of IGF1 production to induce anabolic and metabolic responses at multiple target tissues. In this review, we describe the major changes to this axis during pregnancy, with increasing GH abundance in the maternal circulation across multiple species. This stimulates the secretion of IGFs, whose bioavailability is also increased by proteolytic cleavage of their circulating binding proteins during pregnancy. These changes in turn induce maternal metabolic adaptations to pregnancy and promote placental function and fetal growth, as does exogenous GH or IGF treatment in animal models of normal and compromised pregnancy. Finally, we explore alternative approaches to enhance maternal GH abundance during pregnancy to promote maternal adaptations, placental function and hence fetal growth.
Haemolysis Detection in MicroRNA-Seq from Clinical Plasma Samples
Publisher: MDPI AG
Date: 21-07-2022
Abstract: The abundance of cell-free microRNA (miRNA) has been measured in blood plasma and proposed as a source of novel, minimally invasive biomarkers for several diseases. Despite improvements in quantification methods, there is no consensus regarding how haemolysis affects plasma miRNA content. We propose a method for haemolysis detection in miRNA high-throughput sequencing (HTS) data from libraries prepared using human plasma. To establish a miRNA haemolysis signature we tested differential miRNA abundance between plasma s les with known haemolysis status. Using these miRNAs with statistically significant higher abundance in our haemolysed group, we further refined the set to reveal high-confidence haemolysis association. Given our specific context, i.e., women of reproductive age, we also tested for significant differences between pregnant and non-pregnant groups. We report a novel 20-miRNA signature used to identify the presence of haemolysis in silico in HTS miRNA-sequencing data. Further, we validated the signature set using firstly an all-male cohort (prostate cancer) and secondly a mixed male and female cohort (radiographic knee osteoarthritis). Conclusion: Given the potential for haemolysis contamination, we recommend that assays for haemolysis detection become standard pre-analytical practice and provide here a simple method for haemolysis detection.
Insulin-like growth factors and foetal programming - A workshop report
Publisher: Elsevier BV
Date: 04-2003
Altered Placental Structure Induced by Maternal Food Restriction in Guinea Pigs: A Role for Circulating IGF-II and IGFBP-2 in the Mother?
Publisher: Elsevier BV
Date: 04-2001
Association of Vascular Endothelial Growth Factor <emph type=ital>+936 C/T</emph> Single-Nucleotide Polymorphism With Pregnancies Complicated by Small-for-Gestational-Age Babies
Publisher: American Medical Association (AMA)
Date: 12-2011
DOI: 10.1001/ARCHPEDIATRICS.2011.796
Abstract: To examine whether single-nucleotide polymorphisms (SNPs) in VEGFA (-2578 C/A and +936 C/T) associate with small-for-gestational-age (SGA) pregnancies and to identify their effects on first-trimester placental VEGFA expression. Multicenter prospective cohort study. Adelaide, Australia, and Auckland, New Zealand. A total of 3234 nulliparous pregnant women, their partners, and their infants. The SNPs in the parent-infant trios and first-trimester placentae (n = 74) were genotyped. Placental VEGFA messenger RNA expression was determined by quantitative reverse transcription-polymerase chain reaction. Small for gestational age was defined as a birth weight less than the 10th customized birth weight percentile adjusted for maternal height, weight, parity, and ethnicity and for gestational age at delivery and infant sex. Uterine and umbilical artery Doppler was performed at 20 weeks' gestation, and resistance indices greater than the 90th percentile were considered abnormal. Of 2123 pregnancies, 1176 (55.4%) were uncomplicated and 216 (10.2%) had SGA infants. Neonatal VEGFA +936 C/T SNP associates with SGA (adjusted odds ratio [aOR], 1.6 95% CI, 1.0-2.3), SGA with abnormal Doppler findings (aOR, 3.5 95% CI, 1.8-7.1), lower birth weight (P = .006), customized birth weight percentile (P = .049), and abnormal uterine artery Doppler findings (OR, 2.5 95% CI, 1.2-5.4). Maternal VEGFA +936 C/T associates with abnormal umbilical artery Doppler findings (OR, 1.5 95% CI, 1.1-2.2). VEGFA +936 CT+TT first-trimester placentae have 36% lower VEGFA messenger RNA expression compared with CC (P = .045). Neonatal VEGFA +936 C/T associates with SGA, and the association is stronger for SGA with abnormal uterine or umbilical artery Doppler findings. The SNP also associates with reduced first-trimester placental VEGFA expression, suggesting that it may have a role in the pathogenesis of SGA. Trial Registration clinicaltrials.gov Identifier: ACTRN12607000551493.
Large Scale Gene Expression Meta-Analysis Reveals Tissue-Specific, Sex-Biased Gene Expression in Humans
Publisher: Frontiers Media SA
Date: 13-10-2016
DNA methylation-mediated down-regulation of DNA methyltransferase-1 (DNMT1) is coincident with, but not essential for, global hypomethylation in human placenta
Publisher: Elsevier BV
Date: 03-2010
The vascular endothelial growth factor family in adverse pregnancy outcomes
Publisher: Oxford University Press (OUP)
Date: 11-04-2012
Abstract: Pre-ecl sia, small-for-gestational-age infants, preterm birth and recurrent miscarriage complicate a significant number of pregnancies. The vascular endothelial growth factor (VEGF) family of angiogenic growth factors is implicated in the pathophysiology of these complications. We aimed to elucidate the role of these angiogenic factors in placentation and to evaluate the predictive value of their protein concentrations and genetic variations in pregnancy complications. We performed a systematic search of PubMed, and retrieved original articles. The search included a combination of terms such as VEGF-A, placental growth factor (PlGF), kinase insert domain receptor, fms-like-tyrosine-kinase receptor 1, soluble fms-like-tyrosine-kinase receptor 1, pre-ecl sia, small-for-gestational-age infants, preterm birth, recurrent miscarriage, placenta, prediction and polymorphisms. This review summarizes the current knowledge of the roles of the VEGF family in early placentation and of the abnormalities in maternal plasma and placental expression of angiogenic proteins in adverse pregnancy outcomes compared with normal pregnancy. PlGF and sFLT-1 in combination with other clinical and biochemical markers in late first or second trimester appear to predict early-onset pre-ecl sia with a high sensitivity and specificity. However, VEGF family proteins do not have sufficient power to accurately predict late-onset pre-ecl sia, small-for-gestational age pregnancies or preterm birth. Functional polymorphisms in these angiogenic genes are implicated in pregnancy complications, but their contribution appears to be minor. Although the VEGF family has important roles in normal and complicated pregnancy, the current predictive value of the VEGF family as biomarkers appears to be limited to early-onset pre-ecl sia.
Hypoxia-inducible factor-1α gene polymorphisms in early and late onset preeclampsia in Sinhalese women
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.PLACENTA.2014.04.008
Abstract: Early (EPE) and late (LPE) onset preecl sia are increasingly being recognized as two distinct disorders. Placental vascular defects are more common in EPE. Hypoxia Inducible Factor 1α (HIF1α) regulates the expression of many angiogenic growth factors in the placenta. We studied the association of two polymorphisms in the HIF1α gene (rs11549465 and rs10873142) with EPE and LPE. 175 nulliparous Sinhalese women with preecl sia and 171 normotensive women matched for age, ethnicity, parity and BMI were recruited at two tertiary care hospitals in Colombo. Preecl sia was diagnosed using international guidelines. DNA extracted from peripheral blood was genotyped using Sequenom MassARRAY. HIF1α rs11549465 dominant model and T allele were reduced in women who developed EPE compared to controls [P = 0.002, OR (95% CI) = 0.3 (0.1-0.7)], in preecl tic women who delivered small for gestational age babies [P = 0.02, OR (95% CI) = 0.5 (0.2-0.9)] compared to controls and in women who developed EPE compared to those who developed LPE [P = 0.006, OR (95% CI) = 0.3 (0.1-0.7)]. Our results demonstrate a protective effect of the T allele in LPE and normal pregnancy, which is relatively lacking in EPE due to low prevalence of this protective allele. HIF1α rs11549465 T allele was previously demonstrated to be associated with a higher transcriptional activity and increased angiogenesis. Inherited susceptibility to increased HIF1α expression resulting in the up-regulation of angiogenic genes may mediate a protective effect in normal pregnancy and pregnancy complicated by LPE.
Impact of periconceptional and preimplantation undernutrition on factors regulating myogenesis and protein synthesis in muscle of singleton and twin fetal sheep
Publisher: Wiley
Date: 08-2015
DOI: 10.14814/PHY2.12495
First trimester trophoblasts forming endothelial-like tubes in vitro emulate a ‘blood vessel development’ gene expression profile
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.GEP.2016.05.001
Abstract: Extravillous cytotrophoblasts isolated from first trimester placenta, and immortalised cell lines derived from them, have the intrinsic ability to form endothelial-like tubes when cultured on Matrigel™ extracellular matrix. This in vitro tube formation may model placental angiogenesis and/or endovascular differentiation by trophoblasts. To interpret the relevance of this phenomenon to placental development, we used a gene expression microarray approach to identify which genes and pathways are associated with the tube-forming phenotype of HTR8/SVneo first trimester trophoblasts (HTR8-M), compared with HTR8/SVneo not forming tubes on plastic culture surface (HTR8-P). Furthermore, we used weighted gene co-expression network analysis (WGCNA) of microarray data to identify modules of co-expressed genes underlying the biological processes. There were 481 genes differentially expressed between HTR8-M and HTR8-P and these were significantly enriched for blood vessel development and related gene ontologies. WGCNA clustered the genes into 9 co-expression modules. One module was significantly associated with HTR8-M (p = 1.15E-05) and contained genes involved in actin cytoskeleton organization, cell migration and blood vessel development, consistent with tube formation on Matrigel. Another module was significantly associated with HTR8-P (p = 1.94E-05) and was enriched for genes involved in mitosis, consistent with proliferation by cells on plastic which do not differentiate. Up-regulation of angiogenesis and vascular development pathways in endovascular trophoblasts in vivo could underpin spiral artery remodelling processes, which are defective in preecl tic pregnancies.
Quality control measures for placental sample purity in DNA methylation array analyses
Publisher: Elsevier BV
Date: 12-2019
Maternal folate, one-carbon metabolism and pregnancy outcomes
Publisher: Wiley
Date: 28-07-2021
DOI: 10.1111/MCN.13064
The Gomeroi Gaaynggal Cohort: A Preliminary Study of the Maternal Determinants of Pregnancy Outcomes in Indigenous Australian Women
Publisher: OMICS Publishing Group
Date: 2015
The duration of sexual relationship and its effects on adverse pregnancy outcomes
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.JRI.2018.05.007
Abstract: This study aims to determine if a short duration of sexual relationship is more common among women who experience adverse pregnancy outcomes including gestational hypertension (GHT), preecl sia, small for gestational age (SGA) pregnancies and spontaneous preterm birth (sPTB) with or without abnormal uterine artery Doppler compared to women who have uncomplicated pregnancies. 5591 nulliparous women from the Screening for Pregnancy Endpoints (SCOPE) study were included. The risk for pregnancy complications for women who had a duration of sexual relationship of ≤3 months, 4-6 months, 7-9 months, 10-12 months was compared with women who had a duration of sexual relationship of >12 months. Uterine artery Doppler was performed at 20 ± 1 weeks' gestation. A short duration of sexual relationship (≤3 months) was more common among women with SGA in the presence of abnormal uterine artery Doppler [9.8% vs 3.0%, aOR (95% CI) 3.4 (1.6-7.08] compared to women who had uncomplicated pregnancies. A short duration of sexual relationship (≤3 months) was also more common among women who had abnormal uterine artery Doppler compared to those with normal uterine artery Doppler [6.1% vs 3.1%, aOR (95% CI) = 2.1 (1.4-3.2)]. A short duration of sexual relationship was not associated with preecl sia after adjusting for confounders. A short duration of sexual relationship is more common among women who deliver SGA infants with features of placental insufficiency as indicated by abnormal uterine artery Doppler.
Imprinted and X-linked non-coding RNAs as potential regulators of human placental function
Publisher: Informa UK Limited
Date: 30-09-2014
DOI: 10.4161/EPI.26197
The association of breast feeding for at least six months with hemodynamic and metabolic health of women and their children aged three years: an observational cohort study
Publisher: Springer Science and Business Media LLC
Date: 19-07-2023
DOI: 10.1186/S13006-023-00571-3
Abstract: Breastfeeding is important for both mother and child in reducing risk of future cardiovascular disease. Therefore, it may be an effective method to improve cardio-metabolic health, particularly those who are exposed to pregnancy complications which increase later CVD risk for both mother and child. The aim of this study is to assess differences in cardiometabolic health at three years postpartum in mothers who breastfed for at least six months and their children compared to those who did not. Women and children from the Screening Tests to Predict Poor Outcomes of Pregnancy (STOP) study (2015–2017) were invited to attend a health check-up at three years postpartum. Women’s breastfeeding status at least six months postpartum was ascertained through their child health record. Anthropometric and hemodynamic measurements were taken from women and their children. A fasting blood s le was taken from women to measure blood glucose and lipids. A total of 160 woman-child dyads were assessed in this study. Women who breastfed for at least six months had significantly lower maternal BMI, systolic blood pressure, diastolic blood pressure, mean arterial pressure, central systolic blood pressure, and central diastolic blood pressure than those who did not and this did not change after adjusting for BMI and socioeconomic index in early pregnancy, prenatal smoking and maternal age in early pregnancy. Subgroup analysis on women who had one or more pregnancy complications during the index pregnancy (i.e. preecl sia, gestational hypertension, delivery of a small for gestational age infant, delivery of a preterm infant, and/or gestational diabetes mellitus) demonstrated that women who breastfed for at least six months had significantly lower maternal systolic and diastolic blood pressures, serum insulin and triglycerides, and higher HDL cholesterol. There were no differences in child anthropometric or hemodynamic variables at three years of age between those children who had been breastfed for at least six months and those who had not. Breastfeeding for at least six months may reduce some maternal cardiovascular risk factors in women at three years postpartum, in particular, in those who have experienced a complication of pregnancy. ACTRN12614000985684 (12/09/2014).
The effect of zinc on human trophoblast proliferation and oxidative stress
Publisher: Elsevier BV
Date: 04-2021
The balance between human maternal plasma angiotensin II and angiotensin 1-7 levels in early gestation pregnancy is influenced by fetal sex
Publisher: Hindawi Limited
Date: 25-02-2014
Abstract: There are fetal sex-associated differences in the circulating maternal renin-angiotensin system (RAS) in early pregnancy. Plasma prorenin, angiotensin (Ang) II, Ang 1-7 and angiotensin-converting enzyme (ACE) concentrations were measured at 15 weeks' gestation in 131 women with uncomplicated pregnancies from the Adelaide SCOPE cohort. Uterine and umbilical artery Doppler sonography was performed at 20 weeks' gestation. At 15 weeks, women bearing female fetuses had higher maternal Ang II concentrations (p = 0.017) and lower Ang 1-7 to Ang II ratios (p = 0.016) than women bearing males. In women with male fetuses, Ang II positively correlated with birth weight (p = 0.028) and prorenin negatively correlated with placental weight (p = 0.014). Female fetuses had higher umbilical artery resistance indices (p = 0.019) that were related to maternal prorenin concentrations (p = 0.007). In early human pregnancy, the maternal RAS is influenced by fetal sex. The lower Ang 1-7 to Ang II ratios in women with female fetuses may contribute to the lower maternal peripheral microvascular flow as described previously and the lack of any positive effect of Ang II on fetal growth, as seen in women with male fetuses.
Cord blood DNA methylation biomarkers for predicting neurodevelopmental outcomes
Publisher: MDPI AG
Date: 03-12-2016
DOI: 10.3390/GENES7120117
Isolation of villous cytotrophoblasts from second trimester human placentas
Publisher: Elsevier BV
Date: 12-2018
Anti-Müllerian hormone levels in recurrent embryonic miscarriage patients are frequently abnormal, and may affect pregnancy outcomes
Publisher: Informa UK Limited
Date: 27-03-2019
DOI: 10.1080/01443615.2018.1552669
Abstract: This prospective cohort study measured anti-Müllerian hormone (AMH) levels in recurrent miscarriage (RM) patients, compared them to a normal population, and assessed the pregnancy outcomes. The RM patients demonstrated AMH levels that were significantly lower than the normal population, both in women aged ≤35 years, and those aged >35 years. AMH percentiles were found to be significantly lower in the study group of RM patients ≤35 years (p 35 years (p< .03), were compared to women from a normal population. Serum AMH levels may reflect quality, and quantity of the remaining oocytes in these patients, and RM patients may have a low ovarian reserve, and a potentially poor oocyte quality, as shown by low circulating AMH. The evaluation of AMH levels in a RM work up may allow realistic counselling and possible ART referral in RM patients. Impact statement What is already known on this subject? There is some evidence to show that low AMH levels are associated with recurrent miscarriages and this is thought to be due to a decreased oocyte quality. The AMH levels are lower in the patients with endometriosis, and are often significantly higher in the patients with polycystic ovarian syndrome. Both conditions are independently associated with miscarriages. What the results of this study add? Anti-Müllerian hormone (AMH) levels were found to be significantly lower in recurrent miscarriage patients, compared to a normal population. This may be another factor contributing to miscarriages. The spontaneous pregnancy rates in the miscarriage group significantly improved with increasing AMH levels. This may confirm that patients with low AMH levels have poorer quality oocytes, and thus may be considered 'sub-fertile'. It was also found that the utilisation of assisted reproductive technologies (ART) to achieve a pregnancy was significantly reduced in the groups with a higher serum AMH. What the implications are of these findings for clinical practice and/or further research? Serum AMH levels should be offered to all patients as part of a recurrent miscarriage work up. Detecting the low AMH levels and counselling the patients on these findings may allow them the option of accessing ART. ART may have the ability to expedite conception rates, and with pre-implantation genetic analyses, could possibly select the embryos with the greatest chance of survival. Further research is needed to establish how the decreased AMH levels contribute to recurrent miscarriages.
Somatic cell nuclear transfer in the sheep induces placental defects that likely precede fetal demise
Publisher: Bioscientifica
Date: 2007
DOI: 10.1530/REP.1.01203
Abstract: The efficiency of cloning by somatic cell nuclear transfer (SCNT) is poor in livestock with ~5% of transferred cloned embryos developing to term. SCNT is associated with gross placental structural abnormalities. We aimed to identify defects in placental histology and gene expression in failing ovine cloned pregnancies to better understand why so many clones generated by SCNT die in utero . Placentomes from SCNT pregnancies ( n = 9) and age matched, naturally mated controls ( n = 20) were collected at two gestational age ranges (105–134 days and 135–154 days term = 147 days). There was no effect of cloning on total placental weight. However, cloning reduced the number of placentomes at both gestational ages (105–134 days: control 55.0 ± 4.2, clone 44.7 ± 8.0 and 135–154 days: control 72.2 ± 5.1, clone 36.6 ± 5.1 P 0.001) and increased the mean in idual placentome weight (105–134 days: control 10.6 ± 1.3 g, clone 18.6 ± 2.8 g and 135–154 days: control 6.6 ± 0.6 g, clone 7.0 ± 2.0 g P 0.02). Placentomes from cloned pregnancies had a significant volume of shed trophoblast and fetal villous hemorrhage, absent in controls, at both gestational age ranges ( P 0.001) that was shown to be apoptotic by activated caspase-3 immunoreactivity. Consequently, the volume of intact trophoblast was reduced and the arithmetic mean barrier thickness of trophoblast through which exchange occurs was altered ( P 0.001) at both gestational age ranges in clones. In addition, cloning reduced placental expression of key genes in placental differentiation and function. Thus, cloning by SCNT results in both gross and microscopic placental abnormalities. We speculate that trophoblast apoptosis, shedding, and hemorrhage may be causal in fetal death in ovine clones.
A sexually dimorphic murine model of IUGR induced by embryo transfer
Publisher: Bioscientifica
Date: 02-2021
DOI: 10.1530/REP-20-0209
Abstract: Animal models are needed to develop interventions to prevent or treat intrauterine growth restriction (IUGR). Foetal growth rates and effects of in utero exposures differ between sexes, but little is known about sex-specific effects of increasing litter size. We established a murine IUGR model using pregnancies generated by multiple embryo transfers, and evaluated sex-specific responses to increasing litter size. CBAF1 embryos were collected at gestation day 0.5 (GD0.5) and 6, 8, 10 or 12 embryos were transferred into each uterine horn of pseudopregnant female CD1 mice ( n = 32). Foetal and placental outcomes were measured at GD18.5. In the main experiment, foetuses were genotyped ( Sry ) for analysis of sex-specific outcomes. The number of implantation sites ( P = 0.033) and litter size (number of foetuses, P = 0.008) correlated positively with the number of embryos transferred, while placental weight correlated negatively with litter size (both P 0.01). The relationship between viable litter size and foetal weight differed between sexes (interaction P = 0.002), such that foetal weights of males ( P = 0.002), but not females ( P = 0.233), correlated negatively with litter size. Placental weight decreased with increasing litter size ( P 0.001) and was lower in females than males ( P = 0.020). Our results suggest that male foetuses grow as fast as permitted by nutrient supply, whereas the female maintains placental reserve capacity. This strategy reflecting sex-specific gene expression is likely to place the male foetus at greater risk of death in the event of a ‘second hit’.
Impact of maternal undernutrition around the time of conception on factors regulating hepatic lipid metabolism and microRNAs in singleton and twin fetuses
Publisher: American Physiological Society
Date: 15-01-2016
DOI: 10.1152/AJPENDO.00600.2014
Abstract: We have investigated the effects of embryo number and maternal undernutrition imposed either around the time of conception or before implantation on hepatic lipid metabolism in the sheep fetus. We have demonstrated that periconceptional undernutrition and preimplantation undernutrition each resulted in decreased hepatic fatty acid β-oxidation regulators, PGC-1α ( P 0.05), PDK2 ( P 0.01), and PDK4 ( P 0.01) mRNA expression in singleton and twin fetuses at 135–138 days gestation. In singletons, there was also lower hepatic PDK4 ( P 0.01), CPT-1 ( P 0.01), and PKCζ ( P 0.01) protein abundance in the PCUN and PIUN groups and a lower protein abundance of PDPK-1 ( P 0.05) in the PCUN group. Interestingly, in twins, the hepatic protein abundance of p-AMPK (Ser 485 ) ( P 0.01), p-PDPK-1 (Ser 41 ) ( P 0.05), and PKCζ ( P 0.05) was higher in the PCUN and PIUN groups, and hepatic PDK4 ( P 0.001) and CPT-1 ( P 0.05) protein abundance was also higher in the PIUN twin fetus. We also found that the expression of a number of microRNAs was altered in response to PCUN or PIUN and that there is evidence that these changes may underlie the changes in the protein abundance of key regulators of hepatic fatty acid β-oxidation in the PCUN and PIUN groups. Therefore, embryo number and the timing of maternal undernutrition in early pregnancy have a differential impact on hepatic microRNA expression and on the factors that regulate hepatic fatty acid oxidation and lipid synthesis.
Long-term Trends in Singleton Preterm Birth in South Australia From 1986 to 2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2017
DOI: 10.1097/AOG.0000000000002419
Abstract: To describe long-term trends in the prevalence of preterm birth and rates of preterm birth in singleton pregnancies complicated by hypertensive disorders of pregnancy, small for gestational age (SGA), and preterm prelabor rupture of membranes (PROM) in South Australia. We conducted a retrospective population study including all singleton live births in the state of South Australia from 1986 to 2014. Long-term trends for preterm birth, hypertensive disorders of pregnancy, SGA, preterm PROM as well as stillbirth were assessed using joinpoint regression analyses. Trends in maternal age, body mass index (BMI), ethnic ersity, parity, and smoking over time were also assessed. From 1986 to 2014, with a total of 539,234 singleton births, the overall preterm birth rates increased from 5.1% to 7.1% ( P .001) and for iatrogenic preterm birth increased from 1.6% to 3.2% ( P .001). The incidence of hypertensive disorders of pregnancy decreased from 8.7% to 7.2%. Among pregnancies complicated by hypertensive disorders of pregnancy, the proportion of preterm birth increased (10.4–17.5%, P .001). The incidence of SGA decreased from 11.1% to 8.0%. Among pregnancies complicated by SGA, the proportion of preterm birth increased (2.9–5.4%, P .001). The incidence of preterm PROM increased from 1.4% to 2.2%. Among pregnancies complicated by preterm PROM, the proportion of preterm birth remained stable. Preterm stillbirth rates declined (4.23–2.32%, P .001). Maternal age, BMI, and ethnic ersity have all increased since 1986, whereas maternal smoking has decreased. In South Australia, the preterm birth rate among singletons increased from 1986 to 2014 by 40%, with iatrogenic preterm birth being responsible for 80% of this increase. Incidence of hypertensive disorders of pregnancy and SGA declined. Among pregnancies complicated by hypertensive disorders of pregnancy and SGA, the proportions of preterm birth increased, indicating earlier interventions in these women. The diagnosis of preterm PROM increased from 1% to 2%, and greater than 80% of preterm PROM was associated with preterm birth after 1990. Increasing iatrogenic delivery may be attributable, in part, to changing maternal phenotype and to altered clinicians' behavior. However, improvements in fetal surveillance, particularly ultrasonography, and advanced neonatal care may underpin perinatal clinical decision-making and the likelihood of iatrogenic birth.
Large-scale transcriptome-wide profiling of microRNAs in human placenta and maternal plasma at early to mid gestation
Publisher: Cold Spring Harbor Laboratory
Date: 22-08-2020
DOI: 10.1101/2020.08.19.20177873
Abstract: MicroRNAs (miRNAs) are increasingly seen as important regulators of placental development and opportunistic biomarker targets. Given the difficulty in obtaining s les from early gestation and subsequent paucity of the same, investigation of the role of miRNAs in early gestation human placenta has been limited. To address this, we generated miRNA profiles using 96 placentas from presumed normal pregnancies, across early gestation, in combination with matched profiles from maternal plasma. Placenta s les range from 6–23 weeks’ gestation, a time period that includes placenta from the early, relatively low but physiological (6–10 weeks’ gestation) oxygen environment, and later, physiologically normal oxygen environment (11–23 weeks’ gestation). We identified 637 miRNAs with expression in 86 s les (after removing poor quality s les), showing a clear gestational age gradient from 6–23 weeks’ gestation. We identified 374 differentially expressed (DE) miRNAs between placentas from 6–10 weeks’ versus 11–23 weeks’ gestation. We see a clear gestational age group bias in miRNA clusters C19MC, C14MC, miR-17∼92 and paralogs, regions that also include many DE miRNAs. Proportional change in expression of placenta-specific miRNA clusters was reflected in maternal plasma. The presumed introduction of oxygenated maternal blood into the placenta (between ∼10–12 weeks’ gestation) changes the miRNA profile of the chorionic villus, particularly in placenta-specific miRNA clusters. Data presented here comprise a clinically important reference set for studying early placenta development and may underpin the generation of minimally invasive methods for monitoring placental health.
Abnormal pregnancy outcomes in mice using an induced periodontitis model and the haematogenous migration of Fusobacterium nucleatum sub-species to the murine placenta
Publisher: Public Library of Science (PLoS)
Date: 25-03-2015
Changes in structure of the trophectoderm of a marsupial in mid-pregnancy up to the time of implantation
Publisher: CSIRO Publishing
Date: 1996
DOI: 10.1071/RD9960797
Abstract: Pre- and peri-implantation embryos of the dasyurid marsupial Sminthopsis crassicaudata were examined for morphological differentiation of the trophectoderm. The cells of unilaminar blastocysts were all squamous and stained intensely with toluidine blue. In bilaminar blastocysts and embryos at the early embryonic-disc stage, the trophectoderm was similar in appearance to, but stained more lightly than, the underlying endoderm. Trophoblast differentiation did not appear to occur until the mesoderm had begun to migrate between the trophoblast and endoderm beyond the embryonic disc. At this stage, trophoblasts had three distinct morphologies: (1) vacuolated, tall and columnar cells in the trilaminar region (2) large cuboidal cells in the adjacent bilaminar region and (3) squamous cells in the abembryonic pole of the bilaminar region. These variations in cell structure correlate with differences in subsequent functional activity in these three regions of the yolk sac placenta.
The Placental Response to Excess Maternal Glucocorticoid Exposure Differs Between the Male and Female Conceptus in Spiny Mice1
Publisher: Oxford University Press (OUP)
Date: 11-2011
DOI: 10.1095/BIOLREPROD.111.093369
Abstract: The placenta is the intermediary between the mother and fetus, and its primary role is to provide for the appropriate growth of the fetus. A suboptimal in utero environment has been shown to differentially affect the health of offspring, depending on their sex. Here we show that excess maternal glucocorticoids administered in midgestation (Day 20, 0.5 gestation in the spiny mouse) for 60 h, have persisting effects on the placenta that differ by fetal sex, placental region, and time after glucocorticoid exposure. Dexamethasone (DEX) exposure altered placental structure and mRNA expression from male and female fetuses both immediately (Day 23) and 2 wk posttreatment (Day 37). The immediate consequences (Day 23) of DEX were similar between males and females, with reductions in the expression of IGF1, IGF1R, and SLC2A1 in the placenta. However, by Day 37, the transcriptional and structural response of the placenta was dependent on the sex of the fetus, with placentas of male fetuses having an increase in GCM1 expression, a decrease in SLC2A1 expression, and an increase in the amount of maternal blood sinusoids in the DEX-exposed placenta. Female placentas, on the other hand, showed increased SLC2A1 and MAP2K1 expression and a decrease in the amount of maternal blood sinusoids in response to DEX exposure. We have shown that the effect of a brief glucocorticoid exposure at midgestation has persisting effects on the placenta, and this is likely to have ongoing and dynamic effects on fetal development that differ for a male and female fetus.
Sexual dimorphism in adverse pregnancy outcomes - A retrospective Australian population study 1981-2011
Publisher: Public Library of Science (PLoS)
Date: 11-07-2016
Determinants of Fetal Leptin Synthesis, Fat Mass, and Circulating Leptin Concentrations in Well-Nourished Ewes in Late Pregnancy
Publisher: The Endocrine Society
Date: 11-2003
DOI: 10.1210/EN.2003-0555
Chronic maternal hypertension characterized by renal dysfunction is associated with reduced placental blood flow during late gestation in rabbits
Publisher: American Physiological Society
Date: 04-2010
DOI: 10.1152/AJPREGU.00202.2009
Abstract: Maternal hypertension associated with renal disease is a common pregnancy complication. Previously, we have shown in a rabbit model of mild hypertension that offspring from hypertensive mothers have increased blood pressure as adults. In human pregnancy, hypertension has been associated with decreased utero-placental blood flow. The aim of this study was to determine placental blood flow (PBF) in mild (2-kidney-1-wrapped 2K-1W) and moderate (2-kidney-2-wrapped 2K-2W) rabbit models of maternal hypertension. We hypothesized that PBF would be inversely related to the severity of the hypertension. PBF and renal blood flow (RBF) were measured using microspheres on day 28 of a 32-day gestation, in normotensive (sham), 2K-1W, and 2K-2W hypertensive groups. Mean arterial pressure (MAP, ∼7 mmHg, P 0.05) was increased, and RBF (∼35%, P 0.05) was reduced in the 2K-1W and 2K-2W (MAP ∼20 mmHg, P 0.01 RBF ∼53%, P 0.05) groups compared with the sham group. In the 2K-1W group, PBF fell by ∼12% ( P = 0.08) and fetal-to-placental weight ratio increased by ∼12% ( P 0.01) compared with the sham group, reflecting an increase in the functional capacity of the placenta to deliver nutrients to the fetus. In the 2K-2W group, PBF decreased ∼51% ( P 0.05) compared with the sham group, without changes in placental efficiency. Thus, in late gestation, placental blood flow was significantly reduced in the moderate hypertension group, without accompanying changes in fetal or placental weight or placental efficiency. In contrast, mild hypertension resulted in an increase in placental efficiency, without significant changes in placental blood flow. These findings suggest that mild and moderate hypertension may alter placental delivery of nutrients via differing mechanisms dependent upon the severity of the hypertension.
Impact of serotonin reuptake inhibitor use on breast milk supply in mothers of preterm infants: a retrospective cohort study
Publisher: Wiley
Date: 14-04-2018
DOI: 10.1111/BCP.13575
Impact of embryo number and maternal undernutrition around the time of conception on insulin signaling and gluconeogenic factors and microRNAs in the liver of fetal sheep
Publisher: American Physiological Society
Date: 05-2014
DOI: 10.1152/AJPENDO.00553.2013
Abstract: This study aimed to determine whether exposure of the oocyte and/or embryo to maternal undernutrition results in the later programming of insulin action in the liver and factors regulating gluconeogenesis. To do this, we collect livers from singleton and twin fetal sheep that were exposed to periconceptional (PCUN −60 to 7 days) or preimplantation (PIUN 0–7 days) undernutrition at 136–138 days of gestation (term = 150 days). The mRNA and protein abundance of insulin signaling and gluconeogenic factors were then quantified using qRT-PCR and Western blotting, respectively, and global microRNA expression was quantified using deep sequencing methodology. We found that hepatic PEPCK-C mRNA ( P 0.01) and protein abundance and the protein abundance of IRS-1 ( P 0.01), p110β ( P 0.05), PTEN ( P 0.05), CREB ( P 0.01), and pCREB (Ser 133 P 0.05) were decreased in the PCUN and PIUN singletons. In contrast, hepatic protein abundance of IRS-1 ( P 0.01), p85 ( P 0.01), p110β ( P 0.001), PTEN ( P 0.01), Akt2 ( P 0.01), p-Akt (Ser 473 P 0.01), and p-FOXO-1 (Thr24) ( P 0.01) was increased in twins. There was a decrease in PEPCK-C mRNA ( P 0.01) but, paradoxically, an increase in PEPCK-C protein ( P 0.001) in twins. Both PCUN and PIUN altered the hepatic expression of 23 specific microRNAs. We propose that the differential impact of maternal undernutrition in the presence of one or two embryos on mRNAs and proteins involved in the insulin signaling and gluconeogenesis is explained by changes in the expression of a suite of specific candidate microRNAs.
Circular RNAs in Pregnancy and the Placenta
Publisher: MDPI AG
Date: 20-04-2022
DOI: 10.3390/IJMS23094551
Abstract: The emerging field of circular RNAs (circRNAs) has identified their novel roles in the development and function of many cancers and inspired the interest of many researchers. circRNAs are also found throughout the healthy body, as well as in other pathological states, but while research into the function and abundance of circRNAs has progressed, our overall understanding of these molecules remains primitive. Importantly, recent studies are elucidating new roles for circRNAs in pregnancy, particularly in the placenta. Given that many of the genes responsible for circRNA production in cancer are also highly expressed in the placenta, it is likely that the same genes act in the production of circRNAs in the placenta. Furthermore, placental development can be referred to as ‘controlled cancer’, as it shares many key signalling pathways and hallmarks with tumour growth and metastasis. Hence, the roles of circRNAs in this field are important to study with respect to pregnancy success but also may provide novel insights for cancer progression. This review illuminates the known roles of circRNAs in pregnancy and the placenta, as well as demonstrating differential placental expressions of circRNAs between complicated and uncomplicated pregnancies.
Association Between Maternal Alcohol Consumption in Early Pregnancy and Pregnancy Outcomes
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2013
Cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: systematic review and meta-analysis
Publisher: Cambridge University Press (CUP)
Date: 06-01-2020
DOI: 10.1017/S2040174419000850
Abstract: Gestational diabetes mellitus (GDM) is a pregnancy complication that affects one in seven pregnancies. Emerging evidence demonstrates that children born of pregnancies complicated by GDM may be at increased risk of cardiovascular disease (CVD) in adulthood. Therefore, the aim of this study was to determine cardiovascular risk factors in offspring exposed to GDM in utero . PubMed, CINAHL, SCOPUS, and EMBASE databases were searched. Information was extracted on established CVD risk factors including blood pressure, lipids, blood glucose, fasting insulin, body mass index (BMI), and endothelial/microvascular function. The review protocol is registered in PROSPERO (CRD42018094983). Prospective and retrospective studies comparing offspring exposed to GDM compared to controls (non-GDM pregnancies) were considered. We included studies that defined GDM based on the International Association of Diabetes and Pregnancy Study Groups (IADPSG) definition, or prior definitions. The PRISMA guidelines were followed in conducting this systematic review. Methodological quality was assessed using the Newcastle–Ottawa Quality Assessment Scale. Study selection, data extraction, and quality assessment were done by two independent reviewers. The data were pooled using a random-effects model. Of 59 eligible studies, 24 were included in the meta-analysis. Offspring exposed to GDM had higher systolic blood pressure (mean difference (MD): 1.75 mmHg, 95% CI 0.57–2.94 eight studies, 7264 participants), BMI z -score (MD 0.11, 95% CI 0.02–0.20 nine studies, 8759 participants), and glucose (standard MD 0.43, 95% CI 0.08–0.77 11 studies, 6423 participants) than control participants. In conclusion, offspring exposed to GDM have elevated systolic blood pressure, BMI, and glucose. Those exposed to GDM in utero may benefit from early childhood blood pressure measurements.
The marsupial shell membrane
Publisher: Springer Science and Business Media LLC
Date: 22-03-1996
Abstract: In the dasyurid marsupial, Sminthopsis crassicaudata, as the oocytes/embryos travel down the female reproductive tract two extracellular coats, the mucoid and shell membrane, come to surround them. Embryos recovered from the oviduct have a mucoid coat but no shell membrane which is only found surrounding uterine embryos. Initially, the shell membrane has a compact granular consistency but it later thins and becomes fibrous in texture with fibres oriented mainly in the plane of the membrane. Immunogold labelling with polyclonal antibodies raised against the extracellular coats was employed to determine the location and ultrastructural appearance of the secretory granules which contain mucoid and shell membrane precursors. Secretory granules in the luminal epithelium of the ulla of the oviduct are of irregular electron density, while those in the isthmus are electron-dense and homogeneous. Both types give rise to the mucoid coat. Secretory granules in the epithelia of the utero-tubal junction and some endometrial glands are electron-lucent and contain some flocculent material which, after exocytosis, gives rise to the shell membrane.
Maternal selenium, copper and zinc concentrations in early pregnancy,and the association with fertility
Publisher: MDPI AG
Date: 16-07-2019
DOI: 10.3390/NU11071609
Abstract: Trace elements such as zinc, copper, and selenium are essential for reproductive health, but there is limited work examining how circulating trace elements may associate with fertility in humans. The aim of this study was to determine the association between maternal plasma concentrations of zinc, copper, and selenium, and time to pregnancy and subfertility. Australian women (n = 1060) who participated in the multi-centre prospective Screening for Pregnancy Endpoints study were included. Maternal plasma concentrations of copper, zinc and selenium were assessed at 15 ± 1 weeks’ gestation. Estimates of retrospectively reported time to pregnancy were documented as number of months to conceive subfertility was defined as taking more than 12 months to conceive. A range of maternal and paternal adjustments were included. Women who had lower zinc (time ratio, 1.20 (0.99–1.44)) or who had lower selenium concentrations (1.19 (1.01–1.40)) had a longer time to pregnancy, equivalent to a median difference in time to pregnancy of around 0.6 months. Women with low selenium concentrations were also at a 1.46 (1.06–2.03) greater relative risk for subfertility compared to women with higher selenium concentrations. There were no associations between copper and time to pregnancy or subfertility. Lower selenium and zinc trace element concentrations, which likely reflect lower dietary intakes, associate with a longer time to pregnancy. Further research supporting our work is required, which may inform recommendations to increase maternal trace element intake in women planning a pregnancy.
Quantitative Allele-Specific Expression and DNA Methylation Analysis of H19, IGF2 and IGF2R in the Human Placenta across Gestation Reveals H19 Imprinting Plasticity
Publisher: Public Library of Science (PLoS)
Date: 05-12-2012
massiR: a method for predicting the sex of samples in gene expression microarray datasets
Publisher: Oxford University Press (OUP)
Date: 22-03-2014
DOI: 10.1093/BIOINFORMATICS/BTU161
Abstract: Summary: High-throughput gene expression microarrays are currently the most efficient method for transcriptome-wide expression analyses. Consequently, gene expression data available through public repositories have largely been obtained from microarray experiments. However, the metadata associated with many publicly available expression microarray datasets often lacks s le sex information, therefore limiting the reuse of these data in new analyses or larger meta-analyses where the effect of sex is to be considered. Here, we present the massiR package , which provides a method for researchers to predict the sex of s les in microarray datasets. Using information from microarray probes representing Y chromosome genes, this package implements unsupervised clustering methods to classify s les into male and female groups, providing an efficient way to identify or confirm the sex of s les in mammalian microarray datasets. Availability and implementation: massiR is implemented as a Bioconductor package in R . The package and the vignette can be downloaded at bioconductor.org and are provided under a GPL-2 license. Contact: sam.buckberry@adelaide.edu.au Supplementary information: Supplementary data are available at Bioinformatics online
Animal Models of Preeclampsia: Causes, Consequences, and Interventions
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2020
DOI: 10.1161/HYPERTENSIONAHA.119.14598
Abstract: Preecl sia is a common pregnancy complication, affecting 2% to 8% of pregnancies worldwide, and is an important cause of both maternal and fetal morbidity and mortality. Importantly, although aspirin and calcium are able to prevent preecl sia in some women, there is no cure apart from delivery of the placenta and fetus, often necessitating iatrogenic preterm birth. Preclinical models of preecl sia are widely used to investigate the causes and consequences of preecl sia and to evaluate safety and efficacy of potential preventative and therapeutic interventions. In this review, we provide a summary of the published preclinical models of preecl sia that meet human diagnostic criteria, including the development of maternal hypertension, together with new-onset proteinuria, maternal organ dysfunction, and uteroplacental dysfunction. We then discuss evidence from preclinical models for multiple causal factors of preecl sia, including those implicated in early-onset and late-onset preecl sia. Next, we discuss the impact of exposure to a preecl sia-like environment for later maternal and progeny health. The presence of long-term impairment, particularly cardiovascular outcomes, in mothers and progeny after an experimentally induced preecl sia-like pregnancy, implies that later onset or reduced severity of preecl sia will improve later maternal and progeny health. Finally, we summarize published intervention studies in preclinical models and identify gaps in knowledge that we consider should be targets for future research.
Lifestyle and pregnancy complications in polycystic ovary syndrome: The SCOPE cohort study
Publisher: Wiley
Date: 04-2019
DOI: 10.1111/CEN.13954
Abstract: To investigate the risk of pregnancy complications in women with and without polycystic ovary syndrome after consideration of lifestyle factors. Prospective cohort. Participants (n = 5628) were apparently healthy nulliparous women with singleton pregnancies from the Screening for Pregnancy Endpoints study in New Zealand, Australia, United Kingdom and Ireland. Multivariable regression models were performed assessing the association of self-reported polycystic ovary syndrome status with pregnancy complications with consideration of lifestyle factors at the 15th week of gestation. Women with polycystic ovary syndrome (n = 354) were older, had a higher socio-economic index and body mass index and were less likely to consume alcohol and smoke but more likely to do vigorous exercise and take multivitamins. In univariable analysis, polycystic ovary syndrome was associated with increased risk of gestational diabetes (OR: 2.2, 95% CI: 1.2, 4.0). In multivariable models, polycystic ovary syndrome was only significantly associated with decreased risk of large for gestational age (OR: 0.62, 95% CI: 0.40, 0.98) with a population attributable risk of 0.22%. None of the other outcomes were attributable to polycystic ovary syndrome status. Polycystic ovary syndrome is associated with a lower risk of large for gestational age infants. In this low-risk population, the risk of pregnancy complications was not increased in women with polycystic ovary syndrome who were following a healthy lifestyle. Further studies are warranted assessing the contribution of lifestyle factors to the risk of pregnancy complications in higher risk groups of women with and without polycystic ovary syndrome.
Effect of Interleukin-10 Null Mutation on Maternal Immune Response and Reproductive Outcome in Mice
Publisher: Oxford University Press (OUP)
Date: 2004
Effect of Iodine and Selenium on Proliferation, Viability, and Oxidative Stress in HTR-8/SVneo Placental Cells
Publisher: Springer Science and Business Media LLC
Date: 05-07-2021
Maternal Food Restriction Reduces the Exchange Surface Area and Increases the Barrier Thickness of the Placenta in the Guinea-pig
Publisher: Elsevier BV
Date: 02-2001
A comparison of early pregnancy biomarkers associated with metabolic health between Indian and European women, from the Screening for Pregnancy Endpoints (SCOPE) study: a prospective cohort.
Publisher: Authorea, Inc.
Date: 19-10-2023
Fertility impairment in granulocyte-macrophage colony-stimulating factor-deficient mice
Publisher: Oxford University Press (OUP)
Date: 02-1999
DOI: 10.1095/BIOLREPROD60.2.251
Abstract: Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been identified as a potentially important mediator of intercellular communication in the female reproductive tract, with principal target cells being the large populations of myeloid leukocytes in the cycling and pregnant uterus, the preimplantation embryo, and trophoblast cells of the developing placenta. To determine the physiological significance of this cytokine in reproduction, the fertility of genetically GM-CSF-deficient (GM-/-) mice was examined. Implantation rates were normal in GM-/- mice, and viable pups were produced. However, the mean litter sizes of GM-/- x GM-/- breeding pairs were 25% smaller at weaning than those of GM+/- x GM+/- pairs, due to fetal death late in gestation and early in postnatal life, with a disproportionate loss of male pups. On Day 17 of pregnancy, the mean number of resorbing and malformed fetuses was twice as high in pregnant GM-/- females (21%, vs. 11% in GM+/- females) the mean fetal weight and the mean fetal:placental ratio in surviving conceptuses were diminished by 7% and 6%, respectively and the number of very small fetuses (< 500 mg) was 9-times as high (23% vs. 2.5%). Mortality during the first 3 wk of life was 4.5-times as high in pups born to GM-/- mothers (9%, vs. 2% in GM+/- females), and diminished size persisted in GM-/- pups, particularly males, into adulthood. The detrimental effect of maternal GM-CSF deficiency was less apparent when GM-/- females were mated with GM+/+ males litter sizes at birth and at weaning were not significantly smaller than in GM+/- matings, and fetal weights and fetal:placental ratios were also comparable. When polymerase chain reaction was used to genotype embryonic tissue in heterozygote matings, GM-/- fetuses from GM-/- females were found to be smaller than their GM+/- littermates and smaller than GM-/- fetuses gestated in GM+/- females. The size and distribution of uterine granulocyte and macrophage populations were normal during the estrous cycle, during early pregnancy, and in midgestation. Analysis of placental structure revealed that the ratio of labyrinthine to spongiotrophoblast areas was reduced by approximately 28% in GM-/- placentae, and the proportion of vacuolated trophoblast "glycogen cells" in the spongiotrophoblast layer was diminished. Compromised placental function as a result of subtle developmental aberrations may therefore partially account for embryonic growth retardation in GM-CSF-deficient mice. Collectively, these studies show that fetal growth and viability are jeopardized in the absence of maternal GM-CSF. The detrimental effects are most clearly evident when the conceptus is also GM-CSF deficient, suggesting that GM-CSF of either maternal or fetal origin is required for optimal growth and survival of the fetus in mice.
Maternal diet and offspring telomere length: A systematic review
Publisher: Oxford University Press (OUP)
Date: 23-09-2021
Abstract: Many studies assert a negative influence of inappropriate maternal diet and nutritional status during pregnancy on offspring, not only in utero but throughout life, because of the role in the programing of noncommunicable diseases. Telomere length is a biomarker of aging, and shorter telomeres are associated with chronic disease later in life. Maternal nutrition and nutritional status may be an important determinant of offspring telomere length. A systematic review was conducted to determine the effect of maternal nutrition and nutritional status in pregnancy on offspring telomere length. This systematic review was conducted according to PRISMA guidelines. Database searches of PubMed, CINAHL, Scopus, Medline, and Web of Science were performed. Included studies assessed the association between maternal nutrition (dietary intake and nutritional status) during pregnancy and offspring telomere length measured in cord blood, serum, plasma, and peripheral blood mononuclear cells. Three authors screened and determined the quality of the articles disagreements were resolved by a fourth author. All authors compared the compiled data. Seven studies were extracted and evaluated. Studies comprised a double-blind placebo-controlled trial (n = 1), prospective cohort studies (n = 5), and a cross-sectional study (n = 1). Higher circulating maternal folate and 25-hydroxyvitamin D3 concentrations, along with higher maternal dietary caffeine intakes, were associated with longer offspring telomere length, whereas higher dietary intake of carbohydrate, folate, n-3 polyunsaturated fatty acids, vitamin C, or sodium was not. The limited but suggestive evidence highlights the need for further research to be conducted in this area, particularly longitudinal studies involving larger cohorts of pregnant women. PROSPERO registration no. CRD42019136506
Regulation of the human placental (pro)renin receptor-prorenin-angiotensin system by microRNAs
Publisher: Oxford University Press (OUP)
Date: 28-07-2018
Abstract: Are any microRNAs (miRNAs) that target the placental renin-angiotensin system (RAS) in the human placenta suppressed in early gestation? Overall, 21 miRNAs with predicted RAS mRNA targets were less abundant in early versus term placentae and nine were more highly expressed. Regulation of human placental RAS expression could alter placental development and therefore normal pregnancy outcome. The expression of genes encoding prorenin (REN), angiotensinogen, (pro)renin receptor, angiotensin converting enzyme 2, and the angiotensin II type 1 receptor are highest in early gestation, at a time when oxygen tension is at its lowest. Studies have shown that the human placental RAS is sensitive to oxygen, as are some miRNAs that regulate RAS mRNAs. We propose that in early pregnancy, the prevailing low O2 tension, by suppression of levels of miRNAs that target RAS mRNAs, results in increased expression of RAS mRNAs and encoded proteins. As gestation proceeds and the prevailing oxygen tension rises, abundance of these miRNAs increases, and placental RAS mRNA expression is suppressed. The expression of miRNAs was compared in human placentae collected in early (10-11 weeks n = 7) and mid-gestation (14-18 weeks n = 8) with placenta collected at term (38-40 weeks n = 8). Expression of placental miRNAs in women with early (29-35.1 weeks n = 8) or late-onset pre-ecl sia (PE) (>34-weeks gestation n = 8) and gestational age matched preterm (31.6-35.1 weeks n = 8) and term normotensive controls were also compared. Agilent Human miRNA microarray v19 was used to detect up to 2006 miRNAs in four placentae from each group. Statistically different levels of expression were determined and refined using predictive modelling. Placental miRNAs predicted to target RAS mRNAs were identified in three databases. Differences detected on the array were confirmed for some miRNAs by semi-quantitative RT-PCR (qPCR, n = 7-8 for all groups). Two differentially expressed miRNAs that were known to target human renal REN mRNA (miR-181a-5p and miR-663) were transfected into human HTR-8/SVneo trophoblast cells to examine their effect on placental REN expression and prorenin levels. In early gestation placentae, 186 miRNAs were differentially expressed compared with term placentae (109 increased, 77 decreased). Thirty of the differentially expressed miRNAs were predicted to target RAS components. In mid-gestation placentae, 117 miRNAs were differentially expressed compared with term placentae (69 increased, 48 decreased). Of these, 19 had RAS mRNAs as predicted targets. Eight miRNAs that were lower in early gestation and predicted to target RAS mRNAs were confirmed by qPCR. All showed an increase during gestation and could influence the transgestational profile of the human placental RAS. Additionally, on the array, three miRNAs predicted to target RAS mRNAs (miR-892c-3p, miR-378c and miR-514b-3p) were overexpressed in placentae from women with late-onset PE (P = 3.6E-10, P = 1.8E-05, P = 5.3E-06 respectively). miR-663, which suppresses renal REN mRNA expression, was overexpressed in early-onset PE placentae as determined by qRT-PCR analysis (P = 0.014). Transfection of miR-181a-5p and miR-663 into HTR-8/SVneo trophoblast cells suppressed REN mRNA expression (P = 0.05) and prorenin protein production (P = 0.001). Data can be found via GEO accession number GSE109832. Further validation that the differentially expressed miRNAs do indeed directly target RAS mRNAs and affect placental development and function is required. This study is limited by the small s le size. Therefore independent validation in a larger cohort is required. We propose that suppression of miRNAs that target the placental RAS in early gestation is partly responsible for the increase in RAS expression at this time, in order to promote placental development. Later in pregnancy, we have detected overexpression of several miRNAs in placentae from women with PE. These may prove to be biomarkers for early detection of women at risk of developing PE. Since the placenta produces at least two miRNAs that were found in the kidney to target REN mRNA, and that also target placental REN mRNA, the escape of these miRNAs into the maternal circulation in excess amounts could affect maternal renal REN mRNA production and thereby disturb maternal fluid and electrolyte homoeostasis. This work was supported by the National Health and Medical Research Council, Australia (APP1043537). K.G.P. is supported by an Australian Research Council Future Fellowship (FT150100179). C.T.R. is supported by a Lloyd Cox Professorial Research Fellowship from the University of Adelaide. F.Z.M. is supported by a National Heart Foundation Future Leader Fellowship and Baker Heart and Diabetes Institute Fellowship. The authors declare that they have no competing interests.
Formyl peptide receptor-2 is decreased in foetal growth restriction and contributes to placental dysfunction
Publisher: Oxford University Press (OUP)
Date: 20-12-2017
Abstract: What is the association between placental formyl peptide receptor 2 (FPR2) and trophoblast and endothelial functions in pregnancies affected by foetal growth restriction (FGR)? Reduced FPR2 placental expression in idiopathic FGR results in significantly altered trophoblast differentiation and endothelial function in vitro. FGR is associated with placental insufficiency, where defective trophoblast and endothelial functions contribute to reduced feto-placental growth. The expression of FPR2 in placental tissues from human pregnancies complicated with FGR was compared to that in gestation-matched uncomplicated control pregnancies (n = 25 from each group). Fpr2 expression was also determined in placental tissues obtained from a murine model of FGR (n = 4). The functional role of FPR2 in primary trophoblasts and endothelial cells in vitro was assessed in erse assays in a time-dependent manner. Placentae from third-trimester pregnancies complicated by idiopathic FGR (n = 25) and those from gestation-matched pregnancies with appropriately grown infants as controls (n = 25) were collected at gestation 27-40 weeks. Placental tissues were also collected from a spontaneous CBA/CaH × DBA/2 J murine model of FGR. Placental FPR2/Fpr2 mRNA expression was determined by real-time PCR, while protein expression was examined by immunoblotting and immunohistochemistry. siRNA transfection was used to silence FPR2 expression in primary trophoblasts and in human umbilical vein endothelial cells (HUVEC), and the quantitation of cytokines, chemokines and apoptosis was performed following a cDNA array analyses. Functional effects of trophoblast differentiation were measured using HCGB/β-hCG and syncytin-2 expression as well as markers of apoptosis, tumour protein 53 (TP53), caspase 8, B cell lymphoma 2 (BCL2) and BCL associated X (BAX). Endothelial function was assessed by proliferation, network formation and permeability assays. Placental FPR2/Fpr2 expression was significantly decreased in FGR placentae (n = 25, P < 0.05) as well as in murine FGR placentae compared to controls (n = 4, P < 0.05). FPR2 siRNA (siFPR2) in term trophoblasts significantly increased differentiation markers, HCGB and syncytin-2 cytokines, interleukin (IL)-6, CXCL8 and apoptotic markers, TP53, caspase 8 and BAX, but significantly reduced the expression of the chemokines CXCL12 and its receptors CXCR4 and CXCR7 CXCL16 and its receptor, CXCR6 and cytokine, IL-10, compared with control siRNA (siCONT). Treatment of HUVECs with siFPR2 significantly reduced proliferation and endothelial tube formation, but significantly increased permeability of HUVECs. N/A. Reduced expression of placental FPR2/Fpr2 was observed in the third trimester at delivery after development of FGR, suggesting that FPR2 is associated with FGR pregnancies. However, there is a possibility that the decreased placental FPR2 observed in FGR may be a consequence rather than a cause of FGR, although our in vitro functional analyses using primary trophoblasts and endothelial cells suggest that FPR2 may have a direct or indirect regulatory role on trophoblast differentiation and endothelial function in FGR. This is the first study linking placental FPR2 expression with changes in the trophoblast and endothelial functions that may explain the placental insufficiency observed in FGR. P.M. and P.R.E. received funding from the Australian Institute of Musculoskeletal Science, Western Health, St. Albans, Victoria 3021, Australia. M.L. is supported by a Career Development Fellowship from the National Health and Medical Research Council (NHMRC Grant no. 1047025). Monash Health is supported by the Victorian Government's Operational Infrastructure Support Programme. The authors declare that there is no conflict of interest in publishing this work.
Risk factors for small‐for‐gestational‐age infants by customised birthweight centiles: data from an international prospective cohort study
Publisher: Wiley
Date: 15-11-2010
DOI: 10.1111/J.1471-0528.2010.02737.X
Abstract: To identify clinical and ultrasound variables associated with the birth of small-for-gestational-age (SGA) infants by customised centiles, subclassified according to whether their mothers were normotensive or developed hypertensive complications. Prospective, multicentre cohort study. Participating centres of the Screening for Pregnancy Endpoints (SCOPE) study in Auckland, New Zealand, Adelaide, Australia, Manchester and London, UK, and Cork, Ireland. The 3513 nulliparous participants of the SCOPE study. Women were interviewed at 15 ± 1 weeks, and had ultrasound growth measurements and umbilical and uterine Doppler studies at 20 ± 1 weeks. Variables associated with SGA infants were identified using logistic regression. Small for gestational age (i.e. a birthweight of less than the tenth customised centile), normotensive-SGA and hypertensive-SGA. Comparison groups for statistical analyses were non-SGA, normotensive non-SGA and hypertensive non-SGA. Among 376 (10.7%) SGA infants, 281 (74.7%) were normotensive-SGA and 95 (25.3%) were hypertensive-SGA. Independent risk factors for normotensive-SGA were low maternal birthweight, low fruit intake pre-pregnancy, cigarette smoking, increasing maternal age, daily vigorous exercise, being a tertiary student, head and abdominal circumference of less than the tenth centile and increasing uterine artery Doppler indices at the 20-week scan. Protective factors were: high green leafy vegetable intake pre-pregnancy, and rhesus-negative blood group. Risk factors for hypertensive-SGA were conception by in vitro fertilisation, previous early pregnancy loss and femur length of less than tenth centile at the 20-week scan. Risk factors for infants who are SGA by customised centiles have been identified in a cohort of healthy nulliparous women. A number of these factors are modifiable however, further studies are needed to replicate these findings.
A prospective registry analysis of psychosocial and metabolic health between women with and without metabolic syndrome after a complicated pregnancy
Publisher: Springer Science and Business Media LLC
Date: 21-11-2022
DOI: 10.1186/S12905-022-02035-Y
Abstract: Pregnancy complications affect over one quarter of Australian pregnancies, and this group of mothers is vulnerable and more likely to experience adverse cardiometabolic health outcomes in the postpartum period. Metabolic syndrome is common in this population and may be associated with postpartum mental health issues. However, this relationship remains poorly understood. To compare the differences in psychosocial parameters and mental health outcomes between women with metabolic syndrome and women without metabolic syndrome 6 months after a complicated pregnancy. This study is prospective registry analysis of women attending a postpartum healthy lifestyle clinic 6 months following a complicated pregnancy. Mental health measures included 9-item Patient Health Questionnaire (PHQ-9), 7-item Generalised Anxiety Disorder questionnaire (GAD-7), self-reported diagnosed history of depression, anxiety and/or other psychiatric condition, and current psychotropic medication use. Women with metabolic syndrome reported significantly more subjective mental health concerns, were more likely to have a history of depression and other psychiatric diagnoses and were more likely prescribed psychotropic medications. However, there were no significant differences in PHQ-9 and GAD-7 scores. Amongst new mothers who experienced complications of pregnancy, those with metabolic syndrome represent a particularly vulnerable group with regards to psychosocial disadvantage and mental health outcomes. These vulnerabilities may not be apparent when using common standardised cross-sectional mental health screening tools such as PHQ-9 and GAD-7.
‘Fetal side’ of the placenta: anatomical mis-annotation of carbon particle ‘transfer’ across the human placenta
Publisher: Springer Science and Business Media LLC
Date: 03-12-2021
Accelerated placental aging in early onset preeclampsia pregnancies identified by DNA methylation
Publisher: Future Medicine Ltd
Date: 03-2017
Abstract: Aim: To determine whether dynamic DNA methylation changes in the human placenta can be used to predict gestational age. Materials & methods: Publicly available placental DNA methylation data from 12 studies, together with our own dataset, using Illumina Infinium Human Methylation BeadChip arrays. Results & conclusion: We developed an accurate tool for predicting gestational age of placentas using 62 CpG sites. There was a higher predicted gestational age for placentas from early onset preecl sia cases, but not term preecl sia, compared with their chronological age. Therefore, early onset preecl sia is associated with placental aging. Gestational age acceleration prediction from DNA methylation array data may provide insight into the molecular mechanisms of pregnancy disorders.
Vitamin D Receptor Gene Ablation in the Conceptus Has Limited Effects on Placental Morphology, Function and Pregnancy Outcome
Publisher: Public Library of Science (PLoS)
Date: 29-06-2015
Maternal and Paternal Genomes Differentially Affect Myofibre Characteristics and Muscle Weights of Bovine Fetuses at Midgestation
Publisher: Public Library of Science (PLoS)
Date: 14-01-2013
A functional variant in ANGPT1 and the risk of pregnancies with hypertensive disorders and small-for-gestational-age infants
Publisher: Oxford University Press (OUP)
Date: 28-12-2011
Abstract: Pregnancies complicated by pre-ecl sia and small-for-gestational-age (SGA) infants demonstrate impaired placental vascular remodelling. Angiopoietin-1 (ANG-1) is an angiogenic growth factor which regulates vascular integrity and remodelling. The TT genotype of angiopoietin 1 (ANGPT1) rs2507800 polymorphism has been associated with increased plasma ANG-1 levels compared with the AA genotype. We aimed to investigate the association between ANGPT1 rs2507800 polymorphism and pregnancies complicated by gestational hypertensive disorders and SGA infants. We also aimed to investigate whether the polymorphism was associated with abnormal uterine artery Doppler as a surrogate marker of impaired placental vascular remodelling. Genotyping data of 1361 nulliparous pregnant women, 1226 partners and 1190 infants were analysed. The prevalence of ANGPT1 rs2507800 TT genotype was reduced in women with pre-ecl sia [P = 0.01, adjusted odds ratio (aOR), 0.5 95% confidence interval (CI), 0.3-0.9], hypertensive SGA (P = 0.04, aOR, 0.5 95% CI, 0.2-0.9) and SGA with abnormal uterine artery Doppler (P = 0.009, aOR, 0.4. 95% CI, 0.2-0.8) compared with women with uncomplicated pregnancy. The prevalence of maternal ANGPT1 rs2507800 TT genotype was reduced in women with increased uterine artery resistance index (P = 0.03, aOR, 0.7 95% CI, 0.5-0.9) and bilateral notching of the uterine arteries (P = 0.004, aOR, 0.6 95% CI, 0.4-0.9). These results remained significant after correcting for multiple testing. Maternal ANGPT1 rs2507800 TT genotype is associated with a reduced risk for pre-ecl sia, hypertensive SGA and abnormal uterine artery Doppler. These findings suggest that the TT genotype may protect against these pregnancy disorders by increasing ANG-1 production at the maternal-fetal interface. The ANGPT1 rs2507800 polymorphism may have a potential role in screening women to predict the risk of these pregnancy complications. TRIAL REGISTRY NAME: Screening nulliparous women to identify the combinations of clinical risk factors and/or biomarkers required to predict pre-ecl sia, SGA babies and spontaneous preterm birth.
Effect of 2-glycoprotein I null mutation on reproductive outcome and antiphospholipid antibody-mediated pregnancy pathology in mice
Publisher: Oxford University Press (OUP)
Date: 25-03-2004
IFPA Meeting 2008 Workshops Report
Publisher: Elsevier BV
Date: 03-2009
Mid-Trimester Maternal ADAM12 Levels Differ According to Fetal Gender in Pregnancies Complicated by Preeclampsia
Publisher: Springer Science and Business Media LLC
Date: 02-2015
Bioengineered Microphysiological Placental Models: Towards Improving Understanding of Pregnancy Health and Disease
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.TIBTECH.2021.03.009
Abstract: Driven by a lack of appropriate human placenta models, recent years have seen the introduction of bioengineered in vitro models to better understand placental health and disease. Thus far, the focus has been on the maternal-foetal barrier. However, there are many other physiologically and pathologically significant aspects of the placenta that would benefit from state-of-the-art bioengineered models, in particular, integrating advanced culture systems with contemporary biological concepts such as organoids. This critical review defines and discusses the key parameters required for the development of physiologically relevant in vitro models of the placenta. Specifically, it highlights the importance of cell type, mechanical forces, and culture microenvironment towards the use of physiologically relevant models to improve the understanding of human placental function and dysfunction.
A functional variant in the thrombospondin‐1 gene and the risk of small for gestational age infants
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1111/J.1538-7836.2011.04494.X
Abstract: Thrombospondin-1 (TSP-1) is a prothrombotic and anti-angiogenic glycoprotein expressed in the placenta. A functional single nucleotide polymorphism in the TSP-1 gene (TSP-1 A2210G) is a risk factor for familial premature myocardial infarction. Small for gestational age (SGA) infants are at increased risk of coronary artery disease in adult life and common genetic factors may underlie both conditions. We investigated the association of TSP-1 A2210G in SGA infants and their parents. The 3234 nulliparous pregnant women, their partners and babies were recruited in Adelaide and Auckland to a prospective multicenter cohort study. Amongst 2123 Caucasian women, 216 (10.2%) delivered an SGA infant, defined as birth weight < 10th customized centile adjusted for maternal height, weight, parity and ethnicity, as well as gestational age at delivery and infant sex. Uncomplicated pregnancies served as controls (n = 1185). DNA extracted from peripheral/cord blood or buccal swabs was genotyped using Sequenom MassARRAY. Multivariable logistic regression was used to compare the odds of SGA between the genotype groups adjusting for potential confounders. Paternal (adjOR, 1.4 95% CI 1.0-2.0) and neonatal (adjOR, 1.8 95% CI, 1.1-2.7) TSP-1 A2210G associates with SGA. The maternal polymorphism approaches significance for an association with SGA (adjOR, 1.3 95% CI, 0.9-1.9). Maternal TSP-1 A2210G associates with a reduced maternal birth weight adjusted for gestational age at delivery (P = 0.03). The TSP-1 A2210G polymorphism, which is a risk factor for myocardial infarction, is associated with SGA pregnancies, suggesting that this polymorphism may associate with the risk of vascular disorders across the life course.
Maternal insulin-like growth factor-II promotes placental functional development and fetal growth via the type 2 IGF receptor in guinea pigs
Publisher: Elsevier BV
Date: 04-2008
DOI: 10.1016/J.PLACENTA.2008.01.009
Abstract: In guinea pigs, maternal insulin-like growth factor (IGF) infusion in early-pregnancy enhances placental transport near-term, increasing fetal growth and survival. The effects of IGF-II, but not IGF-I, appear due to enhanced placental labyrinthine (exchange) development. To determine if the type-2 IGF receptor (IGF2R) mediates these distinct actions of exogenous IGF-II in the mother, we compared the impact of IGF-II with an IGF-II analogue, Leu(27)-IGF-II, which only binds the IGF2R. IGF-II, Leu(27)-IGF-II (1mg/kg per day.sc) or vehicle were infused from days 20-38 of pregnancy (term = 67 days) and placental structure and uptake and transfer of [(3)H]-methyl-D-glucose (MG) and [(14)C]-amino-isobutyric acid (AIB) and fetal growth and plasma metabolites, were measured on day 62. Both IGF-II and Leu(27)-IGF-II increased the volume of placental labyrinth, trophoblast and maternal blood space within the labyrinth and total surface area of trophoblast for exchange, compared to vehicle. Leu(27)-IGF-II also reduced the barrier to diffusion (trophoblast thickness) compared to vehicle and IGF-II. Both IGF-II and Leu(27)-IGF-II increased fetal plasma amino acid concentrations and placental transfer of MG to the fetus compared to vehicle, with Leu(27)-IGF-II also increasing AIB transport compared with vehicle and IGF-II. In addition, Leu(27)-IGF-II increased fetal weight compared to vehicle. In conclusion, maternal treatment with IGF-II or Leu(27)-IGF-II in early gestation, induce similar placental and fetal outcomes near term. This suggests that maternal IGF-II in early gestation acts in part via the IGF2R to persistently enhance placental functional development and nutrient delivery and promote fetal growth.
Pregnancy stress, healthy pregnancy and birth outcomes - The need for early preventative approaches in pregnant Australian Indigenous women: A prospective longitudinal cohort 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.
The association of parental methylenetetrahydrofolate reductase polymorphisms (
Publisher: Informa UK Limited
Date: 12-07-2020
Pre-pregnancy fast food and fruit intake is associated with time to pregnancy
Publisher: Oxford University Press (OUP)
Date: 04-05-2018
Abstract: Is preconception dietary intake associated with reduced fecundity as measured by a longer time to pregnancy (TTP)? Lower intake of fruit and higher intake of fast food in the preconception period were both associated with a longer TTP. Several lifestyle factors, such as smoking and obesity, have consistently been associated with a longer TTP or infertility, but the role of preconception diet in women remains poorly studied. Healthier foods or dietary patterns have been associated with improved fertility, however, these studies focused on women already diagnosed with or receiving treatments for infertility, rather than in the general population. This was a multi-center pregnancy-based cohort study of 5628 nulliparous women with low-risk singleton pregnancies who participated in the Screening for Pregnancy Endpoints (SCOPE) study. A total of 5598 women were included. Data on retrospectively reported TTP and preconception dietary intake were collected during the first antenatal study visit (14-16 weeks' gestation). Dietary information for the 1 month prior to conception was obtained from food frequency questions for fruit, green leafy vegetables, fish and fast foods, by a research midwife. Use of any fertility treatments associated with the current pregnancy was documented (yes, n = 340, no, n = 5258). Accelerated failure time models with log normal distribution were conducted to estimate time ratios (TR) and 95% CIs. The impact of differences in dietary intake on infertility (TTP >12 months) was compared using a generalized linear model (Poisson distribution) with robust variance estimates, with resulting relative risks (RR) and 95% CIs. All analyses were controlled for a range of maternal and paternal confounders. Sensitivity analyses were conducted to explore potential biases common to TTP studies. Lower intakes of fruit and higher intakes of fast food were both associated with modest increases in TTP and infertility. Absolute differences between the lowest and highest categories of intake for fruit and fast food were in the order of 0.6-0.9 months for TTP and 4-8% for infertility. Compared with women who consumed fruit ≥3 times/day, the adjusted effects of consuming fruit ≥1-<3 times/day (TR = 1.06, 95% CI: 0.97-1.15), 1-6 times/week (TR = 1.11, 95% CI: 1.01-1.22) or <1-3 times/month (TR = 1.19, 95% CI: 1.03-1.36), corresponded to 6, 11 and 19% increases in the median TTP (Ptrend = 0.007). Similarly, compared with women who consumed fast food ≥4 times/week, the adjusted effects of consuming fast food ≥2- 0-<2 times/week (TR 0.79, 95% CI 0.69-0.89) or no fast food (TR = 0.76, 95% CI: 0.61-0.95), corresponded to an 11, 21 and 24% reduction in the median TTP (Ptrend <0.001). For infertility, compared with women who consumed fruit ≥3 times/day, the adjusted effects of consuming fruit ≥1-<3 times/day, 1-6 times/week or <1-3 times/month corresponded to a 7, 18 and 29% increase in risk of infertility (Ptrend = 0.043). Similarly, compared with women who consumed fast food ≥4 times/week, the adjusted effects of consuming fast food ≥2- 0-<2 times/week, or no fast food, corresponded to an 18, 34 and 41% reduced risk of infertility (Ptrend <0.001). Pre-pregnancy intake of green leafy vegetables or fish were not associated with TTP or infertility. Estimates remained stable across a range of sensitivity analyses. Collection of dietary data relied on retrospective recall and evaluated a limited range of foods. Paternal dietary data was not collected and the potential for residual confounding cannot be eliminated. Compared to prospective TTP studies, retrospective TTP studies are prone to a number of potential sources of bias. These findings underscore the importance of considering preconception diet for fecundity outcomes and preconception guidance. Further research is needed assessing a broader range of foods and food groups in the preconception period. The SCOPE database is provided and maintained by MedSciNet AB (medscinet.com). The Australian SCOPE study was funded by the Premier's Science and Research Fund, South Australian Government (www.dfeest.sa.gov.au/science-research remiers-research-and-industry-fund). The New Zealand SCOPE study was funded by the New Enterprise Research Fund, Foundation for Research Science and Technology Health Research Council (04/198) Evelyn Bond Fund, Auckland District Health Board Charitable Trust. The Irish SCOPE study was funded by the Health Research Board of Ireland (CSA/2007/2 www.hrb.ie). The UK SCOPE study was funded by National Health Service NEAT Grant (Neat Grant FSD025), Biotechnology and Biological Sciences Research council (www.bbsrc.ac.uk/funding GT084) and University of Manchester Proof of Concept Funding (University of Manchester) Guy's and St. Thomas' Charity (King's College London) and Tommy's charity (www.tommys.org/ King's College London and University of Manchester) and Cerebra UK (www.cerebra.org.uk University of Leeds). L.E.G. is supported by an Australian National Health and Medical Research Council (NHMRC) Early Career Fellowship (ID 1070421). L.J.M. is supported by a SACVRDP Fellowship a program collaboratively funded by the National Heart Foundation, the South Australian Department of Health and the South Australian Health and Medical Research Institute. L.C.K. is supported by a Science Foundation Ireland Program Grant for INFANT (12/RC/2272). C.T.R. was supported by a National Health and Medical Research Council (NHMRC) Senior Research Fellowship (GNT1020749). There are no conflicts of interest to declare. Not applicable.
Use of metabolomics for the identification and validation of clinical biomarkers for preterm birth: Preterm SAMBA
Publisher: Springer Science and Business Media LLC
Date: 08-08-2016
Maternal undernutrition reduces P-glycoprotein in guinea pig placenta and developing brain in late gestation
Publisher: Elsevier BV
Date: 06-2012
DOI: 10.1016/J.REPROTOX.2012.01.013
Abstract: Poor nutrition is a major cause of fetal growth restriction which increases neonatal morbidity and mortality, as well as the risk of adult onset diseases. The objective of the study was to determine the effect of maternal undernutrition on P-glycoprotein (P-gp) expression in the placenta and the brain of both the mother and the fetus. Maternal undernutrition in guinea pigs caused placental restriction, and thus decreased fetal weight. Pups in the maternal undernutrition (UN) group had fewer capillaries in the placenta and more capillaries in the brain of the fetus. Placental, maternal and fetal brain MDR1 mRNA expression was the same in the Control and UN groups. Maternal undernutrition resulted in a significant decrease in P-gp protein expression in the placenta and fetal brain, but not the maternal brain. These findings indicate that maternal undernutrition may impact on fetal exposure to drugs administered to the mother during pregnancy due to changes in placental transfer.
Cardio‐metabolic risk factors among young infertile women: a systematic review and meta‐analysis
Publisher: Wiley
Date: 18-03-2020
Vitamin and mineral supplementation in pregnancy: evidence to practice
Publisher: Wiley
Date: 04-2018
DOI: 10.1002/JPPR.1438
Impact of embryo number and periconceptional undernutrition on factors regulating adipogenesis, lipogenesis, and metabolism in adipose tissuein the sheep fetus
Publisher: American Physiological Society
Date: 15-10-2013
DOI: 10.1152/AJPENDO.00180.2013
Abstract: Maternal undernutrition around the time of conception is associated with an increased risk of insulin resistance in adulthood. We hypothesized that maternal undernutrition during the periconceptional (PCUN: −60 to 7 days) and/or preimplantation (PIUN: 0–7 days) periods would result in a decrease in UCP1 expression and the abundance of insulin signaling molecules and an increase in the abundance of factors that regulate adipogenesis and lipogenesis in fetal perirenal adipose tissue (PAT) and that these effects would be different in singletons and twins. Maternal PCUN and PIUN resulted in a decrease in UCP1 expression in PAT, and PIUN resulted in higher circulating insulin concentrations, an increased abundance of pPKCζ and PDK4, and a decreased abundance of Akt1, phosphorylated mTOR, and PPARγ in PAT in singleton and twin fetuses. In singletons, there was also a decrease in the abundance of p110β in PAT in the PCUN and PIUN groups and an increase in total AMPKα in PAT in the PIUN group. In twins, however, there was an increase in the abundance of mTOR in the PCUN group and an increase in PDK2 and decrease in total AMPKα in the PIUN group. Thus exposure to periconceptional undernutrition programs changes in the thermogenic capacity and the insulin and fatty acid oxidation signaling pathway in visceral fat, and these effects are different in singletons and twins. These findings are important, as the thermogenic capacity of brown fat and the insulin sensitivity of visceral fat are important determinants of the risk of developing obesity and an insulin resistance phenotype in later life.
Late pregnancy increases hepatic expression of insulin-like growth factor-I in well nourished guinea pigs
Publisher: Elsevier BV
Date: 04-2005
DOI: 10.1016/J.GHIR.2005.01.002
Abstract: Blood IGF-I concentrations are persistently elevated throughout pregnancy in humans and guinea pigs and may regulate substrate partitioning between mother and conceptus. In the guinea pig, liver and adipose tissue have recently been suggested to contribute to the increased levels of circulating IGF-I in mid-pregnancy, but whether this persists in late pregnancy in undernutrition is not known. Therefore the effect of pregnancy and undernutrition on circulating IGF-I and hepatic expression of IGF-I in late gestation in the guinea pig was examined. Female guinea pigs (Cavia porcellus) were fed ad libitum throughout pregnancy or 70% of ad libitum intake for 28 days prior to and throughout pregnancy (term is 69 d). Non-pregnant animals were maintained for 88 days on the same diets. Plasma IGF-I was measured by RIA after molecular sieving chromatography at low pH. Abundances of IGF-I and beta-actin mRNA in maternal liver were quantified by digoxigenin-ELISA after RT PCR. Late pregnancy increased both the concentration of IGF-I protein (p<0.001) in plasma and the relative abundance of liver IGF-I mRNA (p<0.001) in ad libitum fed, but not in feed restricted pregnant guinea pigs. The concentration of IGF-I protein in plasma correlated positively with the relative abundance of IGF-I mRNA in liver overall (p<0.002), suggesting the liver as a major source of endocrine IGF-I in late pregnant guinea pigs. This study demonstrates that hepatic expression of IGF-I remains elevated during late pregnancy in the well fed guinea pig, which is in contrast to that observed in other non-human species.
Maternal responses to daily maternal porcine somatotropin injections during early-mid pregnancy or early-late pregnancy in sows and gilts
Publisher: Oxford University Press (OUP)
Date: 04-2010
Abstract: Piglet neonatal survival and postnatal growth and efficiency are positively related to birth weight. In gilts, daily maternal porcine ST (pST) injections from d 25 to 100 (term approximately 115 d), but not d 25 to 50, of pregnancy increase progeny birth weight. Daily maternal pST injections from d 25 to 50 increase fetal weight at d 50 in gilts and sows. We therefore hypothesized that daily pST injections from d 25 to 100, but not d 25 to 50, of pregnancy would increase birth weight similarly in both parities. Landrace x Large White gilts and sows were uninjected (controls) or were injected daily with pST (gilts: 2.5 mg/d sows: 4.0 mg/d, each approximately 15 microg of pST/kg per day) from d 25 to 50 or 100 of pregnancy. Litter size and BW were recorded at birth, midlactation, and weaning. Dams were followed through the subsequent mating and pregnancy. Maternal pST injections from d 25 to 100, but not d 25 to 50, increased mean piglet birth weight by 11.6% in sows (P <or= 0.001) and by 5.6% in gilts (P = 0.008). Both pST treatments decreased litter size by approximately 0.6 live-born piglets (each P 0.1) the weaning-remating interval, conception rate, or subsequent litter size. Greater pST-induced birth weight increases in sows than in gilts may mean that underlying metabolic or placental mechanisms for pST action are constrained by maternal competition for nutrients in rapidly growing gilts.
Maternal red blood cell folate concentration at 10-12 weeks gestation and pregnancy outcome
Publisher: Informa UK Limited
Date: 30-11-2012
DOI: 10.3109/14767058.2011.636463
Abstract: To determine if maternal circulating red blood cell (RBC) folate concentration in early pregnancy is associated with late gestation pregnancy complications including small for gestational age (SGA) infants, preecl sia and preterm birth (PTB) in a socioeconomically disadvantaged population. This was a retrospective case control study, conducted at Lyell McEwin Health Service, South Australia, including 400 primiparous women. RBC folate and demographic data were collected at 10-12 weeks gestation. Pregnancy outcome data were obtained from patient case notes. Patients who were folate deficient were more likely to develop pregnancy complications, specifically SGA (OR 6.9, 95% CI 2-24.3) and PTB (OR 5.4 95% CI 1.4-21.2). Those who were folate insufficient were also at increased risk of SGA (OR 3.0, 95% CI 1.3-7.7). No association between folate and preecl sia was found. Women who were supplementing with folic acid delivered infants who were 179 g heavier (5.5% increased birth weight, P = 0.003) and 4.5 days later, compared to those who did not supplement. Furthermore, low RBC folate was associated with cigarette smoking (P < 0.001). Maternal RBC folate concentration in early pregnancy is associated with SGA and PTB, but not with preecl sia.
Child neurodevelopmental outcomes following preterm and term birth: What can the placenta tell us?
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.PLACENTA.2017.06.009
Abstract: A significant proportion of children born preterm will experience some level of neurodevelopmental impairment. Changes in placental function have been observed with many antenatal conditions that are risk factors for preterm birth and/or poor neurodevelopment including fetal growth restriction and in-utero inflammation. This review will highlight placental factors that have been studied to understand the underlying mechanisms and identify biomarkers that lead to poor child neurodevelopmental outcomes. These include changes in gross morphological and histopathological structure and the placental inflammatory response to prenatal infection. Further, we will describe the placenta's role as both a barrier to maternally-derived bioactive substances critical for normal fetal brain development, such as cortisol, and a source of neuroactive steroids and neurotrophins known to have critical functions in neuronal proliferation, axonal growth, myelination and the regulation of apoptosis. Finally, emerging data supporting the potential utility of novel placental biomarkers in the early prediction of poor neurodevelopmental outcome in infants born both preterm and term will be discussed. These include the assessment of genetic variants (e.g. single nucleotide polymorphisms in placental tissue) and epigenetic biomarkers (e.g. placental microRNAs and placental DNA methylation). With the placenta the key tissue regulating the fetal environment, integration of observed changes in placental function with genetic and epigenetic variations may advance our ability to predict future infant health. Ultimately, this may facilitate targeted allocation of health resources with the aim of improving lifelong neurodevelopmental capability.
The obesity-related FTO gene variant associates with the risk of recurrent miscarriage
Publisher: Wiley
Date: 28-04-2015
DOI: 10.1111/AOGS.12640
Abstract: To investigate the association of the fat mass and obesity associated gene (FTO) rs9939609 single nucleotide polymorphism with recurrent miscarriage. Candidate gene association study. Human Genetics Unit, Colombo, Sri Lanka. A total of 202 Sinhalese women with two or more first-trimester miscarriages and no living children (cases) and 202 age- and ethnicity-matched women with no history of miscarriage and having two or more living children (controls). Peripheral blood was collected from the participants and DNA was extracted. Genotyping was performed at the Australian genome Research Facility using the Sequenom MassARRAY system. Genotype and allele frequencies of cases were compared with controls using chi-squared testing. The prevalence of the single nucleotide polymorphism in cases and controls. The mean age of the women in the recurrent miscarriage group was 31.9 ± 0.4 years and that of the control group was 32.3 ± 0.3 years. Of the women in the recurrent miscarriage group, 140 (69.3%) had experienced three or more first-trimester miscarriages. The prevalence of the AA genotype [p = 0.0002, odds ratio (95% CI) = 3.8 (1.8-8.0)] and A allele [p = 0.002, odds ratio (95% CI) = 1.6 (1.2-2.2)] of the FTO rs9939609 single nucleotide polymorphism were increased in women in the recurrent miscarriage group compared with the control group. The obesity-related FTO rs9939609 single nucleotide polymorphism associates with recurrent miscarriage. This finding warrants further investigation with controlling for important factors such as body mass index, diabetes and cardiovascular disease status. The single nucleotide polymorphism may be useful in predicting the risk of recurrent miscarriage.
Maternal marijuana use has independent effects on risk for spontaneous preterm birth but not other common late pregnancy complications
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.REPROTOX.2016.04.021
Abstract: Widespread legalisation of marijuana raises safety concerns for its use in pregnancy. This study investigated the association of marijuana use prior to and during pregnancy with pregnancy outcomes in a prospective cohort of 5588 nulliparous women from the international SCOPE study. Women were assessed at 15±1 and 20±1 weeks' gestation. Cases [278 Preecl sia, 470 gestational hypertension, 633 small-for-gestational-age, 236 spontaneous preterm births (SPTB), 143 gestational diabetes] were compared separately with 4114 non-cases. Although the numbers are small, continued maternal marijuana use at 20 weeks' gestation was associated with SPTB independent of cigarette smoking status [adj OR 2.28 (95% CI:1.45-3.59)] and socioeconomic index (SEI) [adj OR 2.17 (95% CI:1.41-3.34)]. When adjusted for maternal age, cigarette smoking, alcohol and SEI, continued maternal marijuana use at 20 weeks' gestation had a greater effect size [adj OR 5.44 (95% CI 2.44-12.11)]. Our data indicate that increasing use of marijuana among young women of reproductive age is a major public health concern.
Maternal low-dose porcine somatotropin treatment in late gestation increases progeny weight at birth and weaning in sows but not in gilts
Publisher: Oxford University Press (OUP)
Date: 05-2012
Abstract: Birth weight positively predicts postnatal growth and performance in pigs and can be increased by sustained maternal porcine ST (pST) treatment from d 25 to 100 of pregnancy (term ∼115 d). The objective of this study was to test whether a shorter period of maternal pST treatment in late pregnancy (d 75 to 100) could also increase birth and weaning weights of progeny under commercial conditions. Gilts (parity 0) and sows (parities 2 and 3) were not injected (controls) or injected daily with pST (gilts: 2.5 mg•d(-1), sows: 4.0 mg•d(-1), both ∼13 to 14 μg•kg(-1)•d(-1)) from d 75 to 100 of pregnancy. Litter size and BW were recorded at birth and weaning, and dams were followed through the subsequent mating and pregnancy. Maternal pST injections from d 75 to 100 increased litter average progeny weight at birth (+96 g, P = 0.034) and weaning (+430 g, P = 0.038) in sows, but had no effect on progeny weight in gilts (each P > 0.5). Maternal pST treatment did not affect numbers of live-born piglets and increased numbers of stillborn piglets in sows only (+0.4 pigs/litter, P = 0.034). Maternal pST treatment did not affect subsequent reproduction of dams. Together with our previous data, these results suggest that sustained increases in maternal pST are required to increase fetal and postnatal growth in gilt progeny, but that increasing maternal pST in late pregnancy may only be an effective strategy to increase fetal and possibly postnatal growth in sow progeny.
Analysis of Pathogenic Variants Correctable with CRISPR Base Editing among Patients with Recessive Inherited Retinal Degeneration
Publisher: American Medical Association (AMA)
Date: 03-2021
Polymorphisms in the inflammatory pathway genes and the risk of preeclampsia in Sinhalese women
Publisher: Informa UK Limited
Date: 22-04-2016
DOI: 10.3109/14767058.2015.1034102
Abstract: Elevated pro-inflammatory cytokines play an important role in the pathogenesis of preecl sia. We investigated the prevalence of functional polymorphisms in genes regulating inflammation in preecl tic women. One hundred seventy-five nulliparous Sinhalese women with preecl sia (cases) and 171 normotensive women matched for age, ethnicity, parity and body mass index (BMI) (controls) were recruited. Preecl sia was diagnosed using international guidelines. Genotyping was performed on DNA extracted from peripheral blood using the Sequenom MassARRAY system. The prevalence of the CT genotype of IL1A rs17561 polymorphism was increased in preecl tic women compared with controls {p = 0.04, odds ratio (OR) [95% class interval (CI)] = 1.6 (1.0-2.5)}. The prevalence of the CT genotype [p = 0.01, OR (95% CI) = 1.8 (1.1-2.8)] and the dominant model (CT + TT) [p = 0.03, OR (95% CI) = 1.6 (1.1-2.5)] of the IL1A rs1800587 polymorphism were increased in preecl tic women compared with controls. The prevalence of the GA genotype [p = 0.04, OR (95% CI) = 0.6 (0.4-0.9)] and the dominant model (GA + AA) [p = 0.03, OR (95% CI) = 0.6 (0.4-0.9)] of the MBL1 rs1800450 polymorphism were reduced in preecl tic women compared to controls. Genotypes conferring a pro-inflammatory phenotype are increased in preecl tic women.
Rising maternal circulating GH during murine pregnancy suggests placental regulation
Publisher: Bioscientifica
Date: 05-2017
DOI: 10.1530/EC-17-0032
Abstract: Placenta-derived hormones including growth hormone (GH) in humans contribute to maternal adaptation to pregnancy, and intermittent maternal GH administration increases foetal growth in several species. Both patterns and abundance of circulating GH are important for its activity, but their changes during pregnancy have only been reported in humans and rats. The aim of the present study was to characterise circulating profiles and secretory characteristics of GH in non-pregnant female mice and throughout murine pregnancy. Circulating GH concentrations were measured in whole blood (2 μL) collected every 10 min for 6 h in non-pregnant diestrus female C57Bl/6J mice ( n = 9), and pregnant females at day 8.5–9.5 (early pregnancy, n = 8), day 12.5–13.5 (mid-pregnancy, n = 7) and day 17.5 after mating (late pregnancy, n = 7). Kinetics and secretory patterns of GH secretion were determined by deconvolution analysis, while orderliness and regularity of serial GH concentrations were calculated by approximate entropy analysis. Circulating GH was pulsatile in all groups. Mean circulating GH and total and basal GH secretion rates increased markedly from early to mid-pregnancy, and then remained elevated. Pulse frequency and pulsatile GH secretion rate were similar between groups. The irregularity of GH pulses was higher in all pregnant groups than that in non-pregnant mice. Increased circulating GH in murine pregnancy is consistent with an important role for this hormone in maternal adaptation to pregnancy and placental development. The timing of increased basal secretion from mid-pregnancy, concurrent with the formation of the chorioallantoic placenta and initiation of maternal blood flow through it, suggests regulation of pituitary secretion by placenta-derived factors.
Maternal undernutrition during the first week after conception results in decreased expression of glucocorticoid receptor mRNA in the absence of GR exon 17 hypermethylation in the fe
Publisher: Cambridge University Press (CUP)
Date: 30-08-2013
DOI: 10.1017/S2040174413000378
Abstract: Exposure to maternal undernutrition during the periconceptional period results in an earlier prepartum activation of the fetal hypothalamo–pituitary–adrenal (HPA) axis and altered stress responsiveness in the offspring. It is not known whether such changes are a consequence of exposure of the oocyte and/or the early embryo to maternal undernutrition in the periconceptional period. We have compared the effects of ‘periconceptional’ undernutrition (PCUN: maternal undernutrition imposed from at least 45 days before until 6 days after conception), and ‘early preimplantation’ undernutrition (PIUN: maternal undernutrition imposed for only 6 days after conception) on the expression of genes in the fetal anterior pituitary that regulate adrenal growth and steroidogenesis, proopiomelanorcortin (POMC), prohormone convertase 1 (PC1), 11β-hydroxysteroid dehydrogenase type 1 and 2 (11βHSD1 and 2) and the glucocorticoid receptor (GR) in fetal sheep at 136–138 days of gestation. Pituitary GR mRNA expression was significantly lower in the PCUN and PIUN groups in both singletons and twins compared with controls, although this suppression of GR expression was not associated with hypermethylation of the exon 1 7 region of the GR gene. In twin fetuses, the pituitary 11βHSD1 mRNA expression was significantly higher in the PIUN group compared with the PCUN but not the control group. Thus, exposure of the single or twin embryo to maternal undernutrition for only 1 week after conception is sufficient to cause a suppression of the pituitary GR expression in late gestation. These changes may contribute to the increased stress responsiveness of the HPA axis in the offspring after exposure to poor nutrition during the periconceptional period.
The neglected role of insulin-like growth factors in the maternal circulation regulating fetal growth
Publisher: Wiley
Date: 23-12-2011
Non-invasive assessment of maternal hemodynamics in early pregnancy
Publisher: Elsevier BV
Date: 10-2013
DOI: 10.1016/J.PREGHY.2013.07.005
Abstract: Non-invasive assessment of maternal hemodynamics in early pregnancy may be promising in evaluating maternal hemodynamic (mal)adaptation to pregnancy. We explored usage of applanation tonometry and Doppler ultrasound for assessment of cardiac output (CO), systemic vascular resistance (SVR) and arterial stiffness in early pregnancy. Pregnant healthy nulliparous women were studied during first trimester. Radial artery pressure waveform (augmentation index(AIx)), carotid-femoral pulse wave velocity (PWV) and cardiac output (CO) were measured by applanation tonometry (SphygmoCor), electrocardiogram and Doppler ultrasound (USCOM) and related to maternal demographic characteristics and literature concerning advanced pregnancy and non-pregnant subjects. 116 women were studied during gestational age range of 7(+2)-14weeks. Systolic and diastolic central blood pressure were correlated with systolic and diastolic brachial blood pressure respectively. Both measures of arterial stiffness (heart rate corrected AIx(AIx@75) and PWV) were correlated. AIx@75, PWV and SVR were correlated with central mean arterial pressure. CO was negatively correlated with AIx and associated with BMI. PWV was associated with age and BMI, whereas SVR was associated with age. Applanation tonometry and Doppler Ultrasound for assessment of maternal hemodynamics in early pregnancy revealed similar associations between different hemodynamic parameters and maternal characteristics as have previously been reported in advanced pregnancy and non-pregnant subjects. The SphygmoCor and the USCOM appear to be reliable methods for the assessment of maternal hemodynamics in early pregnancy. Obtaining a comprehensive hemodynamic profile using these modalities may offer insight in maternal (mal)adaptation to pregnancy. Future work needs to be done relating such measures to pregnancy outcome.
Erratum to “Epigenetics and Imprinting of the Trophoblast – A Workshop Report” [Placenta 27, supplement A, Trophoblast Research, Vol. 20 S122–S126]
Publisher: Elsevier BV
Date: 09-2006
msgbsR: An R package for analysing methylation-sensitive restriction enzyme sequencing data
Publisher: Springer Science and Business Media LLC
Date: 02-2018
DOI: 10.1038/S41598-018-19655-W
Abstract: Genotyping-by-sequencing (GBS) or restriction-site associated DNA marker sequencing (RAD-seq) is a practical and cost-effective method for analysing large genomes from high ersity species. This method of sequencing, coupled with methylation-sensitive enzymes (often referred to as methylation-sensitive restriction enzyme sequencing or MRE-seq), is an effective tool to study DNA methylation in parts of the genome that are inaccessible in other sequencing techniques or are not annotated in microarray technologies. Current software tools do not fulfil all methylation-sensitive restriction sequencing assays for determining differences in DNA methylation between s les. To fill this computational need, we present msgbsR , an R package that contains tools for the analysis of methylation-sensitive restriction enzyme sequencing experiments. msgbsR can be used to identify and quantify read counts at methylated sites directly from alignment files (BAM files) and enables verification of restriction enzyme cut sites with the correct recognition sequence of the in idual enzyme. In addition, msgbsR assesses DNA methylation based on read coverage, similar to RNA sequencing experiments, rather than methylation proportion and is a useful tool in analysing differential methylation on large populations. The package is fully documented and available freely online as a Bioconductor package ( ackages/release/bioc/html/msgbsR.html ).
Placental Transcription Profiling in 6–23 Weeks’ Gestation Reveals Differential Transcript Usage in Early Development
Publisher: MDPI AG
Date: 19-04-2022
DOI: 10.3390/IJMS23094506
Abstract: The human placenta is a rapidly developing transient organ that is key to pregnancy success. Early development of the conceptus occurs in a low oxygen environment before oxygenated maternal blood begins to flow into the placenta at ~10–12 weeks’ gestation. This process is likely to substantially affect overall placental gene expression. Transcript variability underlying gene expression has yet to be profiled. In this study, accurate transcript expression profiles were identified for 84 human placental chorionic villus tissue s les collected across 6–23 weeks’ gestation. Differential gene expression (DGE), differential transcript expression (DTE) and differential transcript usage (DTU) between 6–10 weeks’ and 11–23 weeks’ gestation groups were assessed. In total, 229 genes had significant DTE yet no significant DGE. Integration of DGE and DTE analyses found that differential expression patterns of in idual transcripts were commonly masked upon aggregation to the gene-level. Of the 611 genes that exhibited DTU, 534 had no significant DGE or DTE. The four most significant DTU genes ADAM10, VMP1, GPR126, and ASAH1, were associated with hypoxia-responsive pathways. Transcript usage is a likely regulatory mechanism in early placentation. Identification of functional roles will facilitate new insight in understanding the origins of pregnancy complications.
Anxiety and Depression in Early Gestation and the Association with Subsequent Gestational Diabetes Mellitus in a Disadvantaged Population
Publisher: Springer Science and Business Media LLC
Date: 12-10-2023
Prevalence of Metabolic Syndrome in Women After Maternal Complications of Pregnancy: An Observational Cohort Analysis
Publisher: Frontiers Media SA
Date: 14-03-2022
Abstract: Certain complications of pregnancy, including hypertensive disorders of pregnancy, gestational diabetes mellitus, intrauterine growth restriction, spontaneous preterm birth, and placental abruption, are established independent risk factors for premature cardiovascular disease in women. Metabolic syndrome, which is associated with an increased risk of cardiovascular disease, may be a suitable alternative to traditional cardiovascular risk calculators that underestimate risk in young women. This study aimed to investigate the prevalence of metabolic syndrome in women who experienced a complicated pregnancy 6 months earlier. This observational study investigated the prevalence of metabolic syndrome as defined by the International Diabetes Federation in all eligible participants ( n = 247) attending a postpartum lifestyle intervention clinic from August 2018 to June 2021 at the Lyell McEwin Hospital in Adelaide, South Australia. A total of 89 (36%) participants met the criteria for metabolic syndrome at a mean follow up time of 7 months postpartum. Almost 90% of the cohort were abdominally obese, and over two thirds of the total cohort met at least two of the criteria for metabolic syndrome. Women with a prior history of one of the common major pregnancy complications are at high risk of future cardiovascular and metabolic disease, with many showing either metabolic syndrome or multiple risk factors at only 7 months postpartum. The results indicate that follow-up within 1 year postpartum is an appropriate time to commence preventative strategies, as many women are already showing early signs of disease.
Early pregnancy maternal trace mineral status and the association with adverse pregnancy outcome in a cohort of Australian women
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.JTEMB.2017.11.016
Abstract: Maternal micronutrient deficiencies in pregnancy can have profound effects on fetal development and pregnancy outcome. Plasma trace minerals including copper, zinc, selenium and iron have been shown to be extremely important in supporting reproduction. We sought to determine whether there is an association between maternal trace mineral status in early pregnancy and pregnancy complications using a prospective cohort study of 1065 pregnant Australian women who were recruited as part of the Screening for Pregnancy Endpoints (SCOPE) study in Adelaide. Copper, zinc, selenium and iron present in the plasma were measured using mass spectrometry in s les collected at 15±1 weeks' gestation. After adjusting for covariates, women with lower plasma copper ( 32.5μmol/L) (aRR=0.87 95% CI=0.76, 0.99 and aRR=0.88 95% CI=0.78, 1.00, respectively). This was also observed when adjusting for plasma zinc and selenium status (<27.9μmol/L: aRR=0.81 95% CI=0.69, 0.96 and 27.9-32.5μmol/L: aRR=0.84 95% CI=0.72, 0.98). Combined low copper and zinc status was also associated with a reduced risk of any pregnancy complication as compared with high copper and zinc status (aRR=0.80 95% CI=0.70, 0.93). These results provide justification for further work into elucidating the mechanistic role of trace elements in early pregnancy, as well as their interactions in supporting successful pregnancy outcomes.
Granulocyte-macrophage colony-stimulating factor alleviates adverse consequences of embryo culture on fetal growth trajectory and placental morphogenesis
Publisher: The Endocrine Society
Date: 05-2005
DOI: 10.1210/EN.2004-1260
Abstract: Growth factors secreted by the female reproductive tract promote development of the preimplantation embryo and potentially act as epigenetic determinants of postimplantation developmental competence and pregnancy outcome. In a comprehensive embryo transfer study in mice, we examined the late gestational and postnatal effects of embryo exposure to the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), identified as a key physiological regulator of cell number and viability in mouse and human blastocysts. Embryo development in culture in the absence of GM-CSF restricted fetal growth, accelerated postnatal growth, and increased adult body mass and adiposity in offspring compared with in vivo-grown embryos, especially in males. Addition of GM-CSF to embryo culture medium increased the proportion of transferred embryos that generated viable progeny and alleviated the effects of in vitro culture on fetal and postnatal growth trajectory but did not prevent programming of adult obesity. Placental morphogenesis was modified by embryo culture, which inhibited development of labyrinthine exchange tissue and adversely altered some structural correlates of placental transfer function. GM-CSF reversed the effect of culture on labyrinthine growth and increased the surface area of placental trophoblast available for nutrient exchange. These findings indicate that the detrimental influence of embryo culture on fetal viability and growth may be largely mediated through altered placental morphogenesis and can be alleviated by GM-CSF. This demonstrates that embryonic exposure to GM-CSF is essential for normal placental development and fetal growth.
Metabolic syndrome and time to pregnancy
Publisher: Wiley
Date: 10-03-2019
Abstract: To determine: (1) the association between metabolic syndrome (MetS), time to pregnancy (TTP), and infertility (2) associations between in idual and an increasing number of MetS components, TTP, and infertility and (3) whether these relationships differ by body mass index (BMI 12 months) were compared using a generalised linear model (Poisson distribution) with robust variance estimates (relative risks, RRs 95% CIs). All analyses (entire cohort and split by BMI) were controlled for a range of maternal and paternal confounding factors. Time to pregnancy and infertility. Of the 5519 women included, 12.4% (n = 684) had MetS. Compared with women without MetS, women with MetS had a longer TTP (adjusted TR 1.30 95% CI 1.15-1.46), which was similar in women who were obese and in women who were not obese. Marginal estimates for median TTP in women with MetS versus without MetS was 3.1 months (3.0-3.3 months) versus 4.1 months (3.6-4.5 months), respectively. Women with MetS were at a 62% greater risk for infertility and were at a greater risk for infertility whether they were obese (adjusted RR 1.62 95% CI 1.15-2.29) or not (adjusted RR 1.73 95% CI 1.33-2.23). Reduced high-density lipoprotein cholesterol (HDL-C) and raised triglycerides (TGs) were the main in idual components associated with risk for infertility. Metabolic syndrome is associated with longer TTP and infertility, independent of obesity. Additional studies, before pregnancy, are required to support our findings and to determine the applicability of which combinations of metabolic abnormalities pose the greatest risk to delayed fertility, or whether in idual components are amenable to modification. Metabolic syndrome is associated with longer time to pregnancy and infertility, independent of obesity.
High Folate, Perturbed One-Carbon Metabolism and Gestational Diabetes Mellitus
Publisher: MDPI AG
Date: 22-09-2022
DOI: 10.3390/NU14193930
Abstract: Folate is a dietary micronutrient essential to one-carbon metabolism. The World Health Organisation recommends folic acid (FA) supplementation pre-conception and in early pregnancy to reduce the risk of fetal neural tube defects (NTDs). Subsequently, many countries (~92) have mandatory FA fortification policies, as well as recommendations for periconceptional FA supplementation. Mandatory fortification initiatives have been largely successful in reducing the incidence of NTDs. However, humans have limited capacity to incorporate FA into the one-carbon metabolic pathway, resulting in the increasingly ubiquitous presence of circulating unmetabolised folic acid (uFA). Excess FA intake has emerged as a risk factor in gestational diabetes mellitus (GDM). Several other one-carbon metabolism components (vitamin B12, homocysteine and choline-derived betaine) are also closely entwined with GDM risk, suggesting a role for one-carbon metabolism in GDM pathogenesis. There is growing evidence from in vitro and animal studies suggesting a role for excess FA in dysregulation of one-carbon metabolism. Specifically, high levels of FA reduce methylenetetrahydrofolate reductase (MTHFR) activity, dysregulate the balance of thymidylate synthase (TS) and methionine synthase (MTR) activity, and elevate homocysteine. High homocysteine is associated with increased oxidative stress and trophoblast apoptosis and reduced human chorionic gonadotrophin (hCG) secretion and pancreatic β-cell function. While the relationship between high FA, perturbed one-carbon metabolism and GDM pathogenesis is not yet fully understood, here we summarise the current state of knowledge. Given rising rates of GDM, now estimated to be 14% globally, and widespread FA food fortification, further research is urgently needed to elucidate the mechanisms which underpin GDM pathogenesis.
Gestational diabetes mellitus and cardio-metabolic risk factors in women and children at 3 years postpartum
Publisher: Springer Science and Business Media LLC
Date: 11-07-2022
DOI: 10.1007/S00592-022-01914-Y
Abstract: Gestational diabetes mellitus (GDM) is thought to be associated with cardio-metabolic risk factor development in women and their children during the early postpartum period and early childhood. We hypothesized that these women and their children would exhibit increased abnormal cardio-metabolic risk factors three years after pregnancy. Women from the Screening Tests to Predict Poor Outcomes of Pregnancy study were invited to attend a follow-up with the child from their index pregnancy at 3 years postpartum. Women and children were assessed for anthropometric measures and haemodynamic function. Fasting blood s les were obtained from women to assess lipid and glucose status. A total of 281 woman-child dyads participated in the 3-year follow-up, with 40 women developing GDM during their index pregnancy. Fasting serum insulin was higher in women with GDM in index pregnancy compared to those with an uncomplicated pregnancy. However, this association was mediated by early pregnancy BMI and socioeconomic index (SEI). The rate of metabolic syndrome was higher in the GDM group than the uncomplicated pregnancy group. Maternal GDM was associated with elevated maternal fasting serum triglycerides at 3 years after adjustment for early pregnancy BMI and SEI. Children exposed to GDM in utero had higher waist circumference compared to children born after an uncomplicated pregnancy, but this is mediated the above covariates. Exposure to GDM is associated with elevated serum triglycerides in women at 3 years postpartum but other cardiometabolic outcomes in women and children appear to be mediated by early pregnancy BMI and SEI.
Beyond oxygen: complex regulation and activity of hypoxia inducible factors in pregnancy
Publisher: Oxford University Press (OUP)
Date: 19-11-2009
Influence of maternal adiposity, preterm birth and birth weight centiles on early childhood obesity in an Indigenous Australian pregnancy-through-to-early-childhood cohort study
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.
Sex- and growth-specific characteristics of small for gestational age infants: a prospective cohort study
Publisher: Springer Science and Business Media LLC
Date: 05-05-2020
DOI: 10.1186/S13293-020-00300-Z
Abstract: Asymmetric fetal growth and male sex are both associated with adverse neonatal outcome. However, less is known about the influence of asymmetric growth and fetal sex within SGA neonates, a group of infants already at increased risk for adverse neonatal outcomes. The aim of the present study was to provide insight into variance in risk factors for SGA in a fetal sex- and growth symmetry-specific way. For this prospective, multicenter cohort study, data from the Screening for Pregnancy Endpoints (SCOPE) study were used with 5628 nulliparous participants, of which 633 (11.3%) pregnancies were complicated with SGA and 3376 (60.0%) women had uncomplicated pregnancies. Association between risk factors for SGA, SGA subgroups, and uncomplicated pregnancies were assessed with multivariable analyses. Prevalence of asymmetric growth varied from 45.8% of SGA infants to 5.5% of infants with a customized birthweight 90th percentile ( p 0.001). Significantly more SGA males had asymmetric growth compared to SGA female infants (51.2% vs 40.4%, p = 0.009). Maternal pre-pregnancy diet and BMI 20 and ≥ 30 were significantly associated with symmetric SGA but not with asymmetric SGA. Asymmetric SGA infants had not only lower customized birthweight percentile (4.4 (SD 2.8) vs 5.0 (SD 3.0), p 0.001), but also lower rates of stillbirth ( p = 0.041) and less often Apgar scores 7 ( p = 0.060). Among SGA infants, low customized birthweight percentiles and male sex are associated with asymmetric growth. Only symmetric SGA is significantly associated with maternal risk factors in early pregnancy. There is a substantial variance in risk factors and neonatal outcomes for SGA based on growth symmetry, implying a different pathogenesis. ACTRN12607000551493
Low Serum Levels of HtrA3 at 15 Weeks of Gestation Are Associated with Late-Onset Preeclampsia Development and Small for Gestational Age Birth
Publisher: S. Karger AG
Date: 2019
DOI: 10.1159/000497144
Abstract: b i Objective: /i /b The aim of this study was to investigate the potential utility of serum HtrA1 and HtrA3, serine proteases that are highly expressed in the developing placenta, at 15 and 20 weeks of gestation for predicting later development of adverse pregnancy outcomes of preecl sia (PE), gestational hypertension (GHT), preterm birth (PTB), and small for gestational age (SGA) birth. b i Methods: /i /b This is a nested case control study of 665 s les (330 controls, 335 cases) from the Adelaide SCOPE cohort. The cases included were 92 PE, 71 GHT, 56 PTB, and 116 SGA. S les were assessed by ELISA and data adjusted for maternal age, BMI, socioeconomic index, hCG, and smoking status. Multivariate logistic regression was performed with other biochemical and biophysical parameters available for these s les. b i Results: /i /b HtrA1 did not differ between the controls and cases. In contrast, HtrA3 was significantly lower at 15 weeks in pregnancies that later developed late-onset PE (LPE) or resulted in SGA birth, with an area under the ROC curve (AUC) of 0.716 and 0.790, respectively. The combination of HtrA3 with PAPP-A, uterine, and umbilical Doppler improved the AUC to 0.755 for LPE and 0.844 for SGA. b i Conclusion: /i /b HtrA3 at 15 weeks is associated with, and may be useful for, the early detection of LPE development and SGA birth.
Robust Early Pregnancy Prediction of Later Preeclampsia Using Metabolomic Biomarkers
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2010
DOI: 10.1161/HYPERTENSIONAHA.110.157297
Abstract: Preecl sia is a pregnancy-specific syndrome that causes substantial maternal and fetal morbidity and mortality. The etiology is incompletely understood, and there is no clinically useful screening test. Current metabolomic technologies have allowed the establishment of metabolic signatures of preecl sia in early pregnancy. Here, a 2-phase discovery/validation metabolic profiling study was performed. In the discovery phase, a nested case-control study was designed, using s les obtained at 15±1 weeks’ gestation from 60 women who subsequently developed preecl sia and 60 controls taking part in the prospective Screening for Pregnancy Endpoints cohort study. Controls were proportionally population matched for age, ethnicity, and body mass index at booking. Plasma s les were analyzed using ultra performance liquid chromatography-mass spectrometry. A multivariate predictive model combining 14 metabolites gave an odds ratio for developing preecl sia of 36 (95% CI: 12 to 108), with an area under the receiver operator characteristic curve of 0.94. These findings were then validated using an independent case-control study on plasma obtained at 15±1 weeks from 39 women who subsequently developed preecl sia and 40 similarly matched controls from a participating center in a different country. The same 14 metabolites produced an odds ratio of 23 (95% CI: 7 to 73) with an area under receiver operator characteristic curve of 0.92. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of preecl sia offers insight into disease pathogenesis and offers the tantalizing promise of a robust presymptomatic screening test.
Zinc is a critical regulator of placental morphogenesis and maternal hemodynamics during pregnancy in mice
Publisher: Springer Science and Business Media LLC
Date: 09-11-2017
DOI: 10.1038/S41598-017-15085-2
Abstract: Zinc is an essential micronutrient in pregnancy and zinc deficiency impairs fetal growth. We used a mouse model of moderate zinc deficiency to investigate the physiological mechanisms by which zinc is important to placental morphogenesis and the maternal blood pressure changes during pregnancy. A 26% reduction in circulating zinc (P = 0.005) was exhibited in mice fed a moderately zinc-deficient diet. Zinc deficiency in pregnancy resulted in an 8% reduction in both near term fetal and placental weights (both P 0.0001) indicative of disrupted placental development and function. Detailed morphological analysis confirmed changes to the placental labyrinth microstructure. Continuous monitoring of maternal mean arterial pressure (MAP) revealed a late gestation decrease in the zinc-deficient dams. Differential expression of a number of regulatory genes within maternal kidneys supported observations on MAP changes in gestation. Increased MAP late in gestation is required to maintain perfusion of multiple placentas within rodent pregnancies. Decreased MAP within the zinc-deficient dams implies reduced blood flow and nutrient delivery to the placenta. These findings show that adequate zinc status is required for correct placental morphogenesis and appropriate maternal blood pressure adaptations to pregnancy. We conclude that insufficient maternal zinc intake from before and during pregnancy is likely to impact in utero programming of offspring growth and development largely through effects to the placenta and maternal cardiovascular system.
New Light on Early Post-Implantation Pregnancy in the Mouse: Roles for Insulin-Like Growth Factor-II (IGF-II)?
Publisher: Elsevier BV
Date: 04-2007
DOI: 10.1016/J.PLACENTA.2006.04.006
Abstract: Successful placental development and the associated changes to the decidual vasculature during early pregnancy are critical to pregnancy outcome. This study utilised immunohistochemistry to provide a photomicrographic account of trophoblast invasion, as well as the changes in the uterine vasculature in the decidua from days 5.5 to 10.5 of murine pregnancy. The pattern of trophoblast invasion during this time is particularly interesting because, unlike in humans, murine trophoblast giant cells (TGCs) do not invade the endometrium in idually but remain in close contact with the expanding giant cell layer. Therefore, trophoblast cells are unlikely to play a direct role in remodelling the maternal vessels in early to mid pregnancy. Nevertheless, the decidual vessels appear to undergo extensive angiogenesis and remodelling to form a network of dilated vessels that presumably maximize placental blood supply. Importantly, the vessels closest to the conceptus lacked a smooth muscle layer throughout early pregnancy and therefore cannot strictly be described as spiral arterioles. TGCs may secrete molecules that can act to induce these vascular changes. Here we show that insulin-like growth factor-II (IGF-II) is expressed throughout early pregnancy in the entire conceptus including trophoblast cells, supporting its role in promoting early placental growth. In addition, the co-localisation of IGF-II and both IGF receptors in the developing blood vessels and/or adjacent stromal cells in the mesometrial, but not in the anti-mesometrial, decidua suggest that IGF-II, upon binding to one of these receptors, may play a role in both decidual angiogenesis and placental differentiation.
Single-nucleotide polymorphisms in the KDR gene in pregnancies complicated by gestational hypertensive disorders and small-for-gestational-age infants
Publisher: Springer Science and Business Media LLC
Date: 05-2012
Abstract: Pregnancies complicated by preecl sia and small-for-gestational-age (SGA) infants share placental vascular abnormalities and both disorders confer increased risk of later life coronary artery disease. Kinase insert domain receptor (KDR) is the main receptor for vascular endothelial growth factor A, a potent angiogenic factor which regulates the development of the placental vasculature. Two polymorphisms in KDR (-604T/C and Val297Ile) are known to be associated with coronary artery disease. We investigated the association of these polymorphisms with preecl sia, gestational hypertension, and SGA infants. Nulliparous pregnant women, their partners, and infants were recruited to a prospective cohort study (n = 1169). Doppler ultrasound of the uterine and umbilical arteries was performed at 20 weeks of gestation. Preecl sia, gestational hypertension, and SGA were defined according to international guidelines. DNA extracted from peripheral venous or cord blood was genotyped using the Sequenom MassARRAY system. Multivariable logistic regression was used to compare the odds for the pregnancy complications between the genotype groups adjusting for potential confounders. Among 937 Caucasian pregnancies, 427 (45.6%) were uncomplicated, 75 (8.0%) developed preecl sia, 102 (10.9%) developed gestational hypertension, and 72 (7.7%) had SGA infants in the absence of maternal hypertensive disease. Paternal and neonatal KDR-604T/C was associated with preecl sia (adjusted odds ratio [aOR] 1.6, 95% confidence interval [CI] 1.0-3.0 and aOR 2.2, 95% CI 1.0-4.4), SGA (aOR 1.9, 95% CI 1.1-3.3 and aOR 2.2, 95% CI 1.2-3.9), and SGA with abnormal Doppler (aOR 2.7, 95% CI 1.2-5.9 and aOR 3.2, 95% CI 1.2-5.9). Paternal and neonatal carriage of the KDR-604T/C polymorphism is associated with the risk of preecl sia and SGA infants.
Periconceptional Undernutrition Programs Changes in Insulin-Signaling Molecules and MicroRNAs in Skeletal Muscle in Singleton and Twin Fetal Sheep1
Publisher: Oxford University Press (OUP)
Date: 2014
DOI: 10.1095/BIOLREPROD.113.109751
Abstract: Maternal undernutrition around the time of conception is associated with an increased risk of insulin resistance in adulthood. We determined the effect of maternal undernutrition in the periconceptional period (PCUN, i.e., 60 days prior to 6 days after conception) and the preimplantation period (PIUN, i.e., 0-6 days after conception) on mRNA expression and protein abundance of key insulin-signaling molecules as well as the global microRNA expression in quadriceps muscle of singleton and twin fetal sheep in late gestation. In singleton fetuses, exposure to PCUN resulted in lower protein abundance of PIK3CB (P < 0.01), PRKCZ (P < 0.05), and pPRKCZ (Thr410) (P < 0.05) in skeletal muscle compared to controls. In PIUN singletons, there was a higher protein abundance of IRS1 (P < 0.05), PDPK1 (P < 0.05), and SLC2A4 (P < 0.05) compared to controls. In twins, PCUN resulted in higher protein abundance of IRS1 (P < 0.05), AKT2 (P < 0.05), PDPK1 (P < 0.05), and PRKCZ (P < 0.001), while PIUN also resulted in higher protein abundance of IRS1 (P < 0.05), PRKCZ (P < 0.001), and SLC2A4 (P < 0.05) in fetal muscle compared to controls. There were specific patterns of the types and direction of changes in the expression of 22 microRNAs in skeletal muscle after exposure to PCUN or PIUN and clear differences in these patterns between singleton and twin pregnancies. These findings provide evidence that maternal undernutrition around the time of conception induces changes in the expression of microRNAs, which may play a role in altering the abundance of the key insulin-signaling molecules in skeletal muscle and in the association between PCUN undernutrition and insulin resistance in adult life.
Placental expression of VEGF family mRNA in adverse pregnancy outcomes
Publisher: Elsevier BV
Date: 06-2012
DOI: 10.1016/J.PLACENTA.2012.02.013
Abstract: The pregnancy complications preecl sia, gestational hypertension, small for gestational age infants (SGA) and pre-term birth (PTB) affect approximately 21% of all pregnancies. The Vascular Endothelial Growth Factor family (VEGF) is implicated in the pathogenesis of these complications. We aimed to evaluate the placental mRNA expression of VEGFA, PGF, FLT1 and KDR in pregnancies complicated by preecl sia, gestational hypertension, SGA infants and pre-term birth. Placentae were collected at delivery from women with pregnancies complicated by preecl sia (n = 18), gestational hypertension (n = 15), normotensive SGA infants (n = 13), late spontaneous pre-term birth (n = 10) and uncomplicated pregnancy (n = 30). RNA was extracted and VEGFA, PGF, FLT1 and KDR expression were quantified using qRT-PCR. Kruskal Wallis test was used to compare placental mRNA expression in the adverse pregnancy outcome groups compared to uncomplicated term pregnancy. Compared to placental mRNA from uncomplicated pregnancies, VEGFA (p = 0.006), PGF (p < 0.001), KDR (p < 0.001) and FLT1 (p = 0.02) mRNA were reduced in preecl tic placentae VEGFA (p < 0.001), PGF (p = 0.01) and KDR (p = 0.008) mRNA were reduced in placentae from pregnancies complicated by gestational hypertension VEGFA (p = 0.03) mRNA was reduced in normotensive SGA pregnancies VEGFA (p = 0.008), PGF (p = 0.01), KDR (p = 0.04) and FLT1 (p = 0.02) mRNA were reduced in placentae from late PTB. VEGF family of angiogenic growth factor mRNA expression in the placenta is reduced in gestational hypertensive disorders, SGA and in pre-term birth.
Improving pregnancy outcomes in humans through studies in sheep.
Publisher: American Physiological Society
Date: 12-2018
DOI: 10.1152/AJPREGU.00391.2017
Abstract: Experimental studies that are relevant to human pregnancy rely on the selection of appropriate animal models as an important element in experimental design. Consideration of the strengths and weaknesses of any animal model of human disease is fundamental to effective and meaningful translation of preclinical research. Studies in sheep have made significant contributions to our understanding of the normal and abnormal development of the fetus. As a model of human pregnancy, studies in sheep have enabled scientists and clinicians to answer questions about the etiology and treatment of poor maternal, placental, and fetal health and to provide an evidence base for translation of interventions to the clinic. The aim of this review is to highlight the advances in perinatal human medicine that have been achieved following translation of research using the pregnant sheep and fetus.
Association between metabolic syndrome and gestational diabetes mellitus in women and their children: a systematic review and meta-analysis
Publisher: Springer Science and Business Media LLC
Date: 15-09-2021
DNA damage and health in pregnancy
Publisher: Elsevier BV
Date: 05-2011
DOI: 10.1016/J.JRI.2011.02.004
Abstract: In healthy pregnancy reactive oxygen species and antioxidants remain in balance and DNA damage is repaired effectively. However, pregnancy is an inflammatory state exhibiting increased susceptibility to oxidative stress such that this balance can be easily disrupted. Increased DNA damage has been shown to be involved in many pathological states including pregnancy complications. Modern lifestyles including exposure to pollutants, poor diet, and lack of exercise cause excess inflammation, oxidative stress, and ultimately DNA damage. There is a growing body of literature providing evidence that these lifestyle changes are increasing our risk of infertility, miscarriage, and late-gestation pregnancy complications. Moreover, baseline DNA damage rises with age and couples in developed societies are delaying childbirth, placing them at further risk. In order to understand the effect of lifestyle and DNA damage on pregnancy health we require large prospective studies, with the collection of s les prior to conception and endpoints of time-to-pregnancy, early pregnancy loss, and late-gestation maternal and fetal health.
The etiology of preeclampsia: The role of the father
Publisher: Elsevier BV
Date: 05-2011
DOI: 10.1016/J.JRI.2010.12.010
Abstract: Preecl sia is often considered as simply a maternal disease with variable degrees of fetal involvement. More and more the unique immunogenetic maternal-paternal relationship is appreciated, and also the specific 'genetic conflict' that is characteristic of haemochorial placentation. From that perspective, pre-ecl sia can be seen as a disease of an in idual couple with primarily maternal and fetal manifestations. The maternal and fetal genomes perform different roles during development. Heritable paternal, rather than maternal, imprinting of the genome is necessary for normal trophoblast development. Large population studies have estimated that 35% of the variance in susceptibility to preecl sia is attributable to maternal genetic effects 20% to fetal genetic effects (with similar contributions of both parents), 13% to the couple effect, less than 1% to the shared sibling environment and 32% to unmeasured factors. Not one of these large population studies focussed on the paternal contribution to preecl sia, which is demonstrated by (1) the effect of the length of the sexual relationship (2) the concept of primipaternity versus primigravidity and (3) the existence of the so-called 'dangerous' father, as demonstrated in various large population studies. It is currently unknown how the father exerts this effect. Possible mechanisms include seminal cytokine levels and their effect on maternal immune deviation, specific paternal HLA characteristics and specific paternal single nucleotide polymorphisms (SNPs), in particular in the paternally expressed genes affecting placentation. Several large cohort studies, including the large international SCOPE consortium, have identified paternal SNPs with strong associations with preecl sia.
Maternal insulin-like growth factor 1 and 2 differentially affect the renin–angiotensin system during pregnancy in the guinea pig
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.GHIR.2015.02.001
Abstract: Insulin-like growth factors (IGFs) are known to interact with the renin-angiotensin system (RAS). We previously demonstrated that administration of IGF1 to guinea pigs in early to mid pregnancy promotes placental function and fetal growth in mid to late gestation. Early administration of IGF2 had sustained, but not acute, effects on these parameters and also on placental structural differentiation. Here, we aimed to determine whether the IGFs interact with the placental RAS in early to mid gestation to modulate placental development and increase fetal growth and survival, and if IGF2 binding the IGF2R is implicated in the sustained effects of IGF2 treatment. At day 20 of pregnancy, guinea pigs were infused with 1m g/kg/day of IGF1, IGF2, (Leu27)IGF2 or vehicle for 18days and sacrificed on either day 62 (late pregnancy) or during the infusion period on day 35 (early-mid pregnancy). Placental structure at day 35 was analyzed using morphometric technique and expression of RAS genes in the placenta and placental and plasma renin activity were measured at both time points. Compared with vehicle at day 35 of gestation, IGF1 infusion reduced the total midsagittal cross-sectional area of the placenta (-17%, p = 0.02) and the labyrinth area (-22%, p = 0.014) but did not alter the labyrinth volume nor labyrinth:interlobium ratios. IGF2 treatment did not affect placental structure. IGF1 did not alter placental mRNA for any of the RAS genes quantified at day 35 (AGTR1, ACE, AGT, TGFB1) but increased TGFB1 expression by more than 16-fold (p = 0.005) at day 62. IGF2 increased placental expression of AGTR1 (+88%, p = 0.03) and decreased AGT (-73%, p = 0.01) compared with the vehicle-treated group at day 35, and both IGF2 and (Leu27)IGF2 increased expression of TGFB1 at day 62 by 9-fold (p = 0.016) and 6-fold (p = 0.019) respectively. Both IGFs increased the ratio of active:total placental renin protein (+22% p = 0.026 p = 0.038) compared to vehicle compared to vehicle at day 35 but not 62. At day 62, IGF2-treated mothers showed a marked increase in total plasma renin (+495%) and active renin (+359%) compared to vehicle but decreased the ratio of active to total renin by 41% (p = 0.042). (Leu27)IGF2-treated animals had higher levels of placental active renin (+73%, p = 0.001) and total renin (+71%, p = 0.001) compared with the vehicle control. The data obtained in the current study suggest the potential for alternate roles for the induction of the RAS after IGF treatment. IGF1 and 2 treatments increase the activation of prorenin to renin in the placenta, possibly due to increased protease activity. In addition, IGF2 treatment in early pregnancy may enhance the maternal adaptation to pregnancy through stimulation of renin in the kidney. The sustained effects on placental differentiation and function after IGF2 treatment suggest therapeutic potential for exogenous administration of IGFs in improving pregnancy outcomes.
Clinical and biochemical factors associated with preeclampsia in women with obesity
Publisher: Wiley
Date: 23-12-2017
DOI: 10.1002/OBY.21715
Integrative transcriptome metaanalysis reveals widespread sex-biased gene expression at the human fetal-maternal interface
Publisher: Oxford University Press (OUP)
Date: 27-05-2014
Placental transcription profiling in 6-23 weeks’ gestation reveals differential transcript usage in early development
Publisher: Cold Spring Harbor Laboratory
Date: 07-03-2022
DOI: 10.1101/2022.03.03.22271882
Abstract: The human placenta is a rapidly developing transient organ that is key to pregnancy success. Early development of the conceptus occurs in a low oxygen environment before oxygenated maternal blood begins to flow into the placenta at ∼10-12 weeks’ gestation. This process is likely to substantially affect overall placental gene expression. Transcript variability underlying gene expression has yet to be profiled. In this study, accurate transcript expression profiles were identified for 84 human placental chorionic villus tissue s les collected across 6-23 weeks’ gestation. Differential gene expression (DGE), differential transcript expression (DTE) and differential transcript usage (DTU) between 6-10 weeks’ and 11-23 weeks’ gestation groups were assessed. In total, 229 genes had significant DTE yet no significant DGE. Integration of DGE and DTE analyses found that differential expression patterns of in idual transcripts were commonly masked upon aggregation to the gene-level. Of the 611 genes that exhibited DTU, 534 had no significant DGE or DTE. The four most significant DTU genes ADAM10, VMP1, GPR126 , and ASAH1 , were associated with hypoxia-responsive pathways. Transcript usage is a likely regulatory mechanism in early placentation. Identification of functional roles will facilitate new insight in understanding the origins of pregnancy complications.
Maternal undernutrition around the time of conception and embryo number each impact on the abundance of key regulators of cardiac growth and metabolism in the fetal sheep heart
Publisher: Cambridge University Press (CUP)
Date: 05-08-2013
DOI: 10.1017/S2040174413000354
Abstract: Poor maternal nutrition before and during pregnancy is associated with an increased risk of cardiovascular disease in later life. To determine the impact of maternal undernutrition during the periconceptional (PCUN: −45 days to 6 days) and preimplantation (PIUN: 0–6 days) periods on cardiac growth and metabolism, we have quantified the mRNA and protein abundance of key regulators of cardiac growth and metabolism in the left ventricle of the sheep fetus in late gestation. The cardiac protein abundance of AMP-activated protein kinase (AMPK), phospho-acetyl CoA carboxykinase (ACC) and pyruvate dehydrogenase kinase-4 (PDK-4) were decreased, whereas ACC was increased in singletons in the PCUN and PIUN groups. In twins, however, cardiac ACC was decreased in the PCUN and PIUN groups, and carnitine palmitoyltransferase-1 (CPT-1) was increased in the PIUN group. In singletons, the cardiac abundance of insulin receptor β (IRβ) was decreased in the PCUN group, and phosphoinositide-dependent protein kinase-1 (PDPK-1) was decreased in the PCUN and PIUN groups. In twins, however, the cardiac abundance of IRβ and phospho-Akt substrate 160kDa (pAS160) were increased in the PIUN group. The cardiac abundance of insulin-like growth factor-2 receptor (IGF-2R), protein kinase C alpha (PKCα) and mammalian target of rapamycin (mTOR) were decreased in PCUN and PIUN singletons and extracellular-signal-regulated kinase (ERK) was also decreased in the PIUN singletons. In contrast, in twins, cardiac abundance of IGF-2R and PKCα were increased in the PCUN and PIUN groups, phospho-ribosomal protein S6 (pRPS6) was increased in the PCUN group, and ERK and eukaryotic initiation factor 4E (eIF4E) were also increased in the PIUN fetuses. In conclusion, maternal undernutrition limited to around the time of conception is sufficient to alter the abundance of key factors regulating cardiac growth and metabolism and this may increase the propensity for cardiovascular diseases in later life.
IFPA meeting 2015 workshop report II: mechanistic role of the placenta in fetal programming; biomarkers of placental function and complications of pregnancy
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.PLACENTA.2015.12.012
Abstract: Workshops are an integral component of the annual International Federation of Placenta Association (IFPA) meeting, allowing for networking and focused discussion related to specialized topics on the placenta. At the 2015 IFPA meeting (Brisbane, Australia) twelve themed workshops were held, three of which are summarized in this report. These workshops focused on various aspects of placental function, particularly in cases of placenta-mediated disease. Collectively, these inter-connected workshops highlighted the role of the placenta in fetal programming, the use of various biomarkers to monitor placental function across pregnancy, and the clinical impact of novel diagnostic and surveillance modalities in instances of late onset fetal growth restriction (FGR).
Do raised two-hour pre-pregnancy insulin levels confer the same risks of developing GDM, as raised fasting levels, in recurrent miscarriage patients?
Publisher: Informa UK Limited
Date: 02-12-2020
DOI: 10.1080/01443615.2019.1672139
Abstract: This study questioned whether raised pre-pregnancy two-hour (2 h) insulin levels, measured in recurrent embryonic miscarriage (RM) patients via a 75 g Oral Glucose Tolerance Test (OGTT), are associated with an increased risk of gestational diabetes mellitus (GDM) in a subsequent pregnancy. Patients had a 75 g OGTT and insulin levels evaluated (
The association of AGTR2 polymorphisms with preeclampsia and uterine artery bilateral notching is modulated by maternal BMI
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.PLACENTA.2012.10.007
Abstract: This study aimed to determine the association of AGTR1 and AGTR2 polymorphisms with preecl sia and whether these are affected by environmental factors and fetal sex. Overall 3234 healthy nulliparous women, their partners and babies were recruited prospectively to the SCOPE study in Adelaide and Auckland. Data analyses were confined to 2121 Caucasian parent-infant trios, among whom 123 had preecl tic pregnancies. 1185 uncomplicated pregnancies served as controls. DNA was extracted from buffy coats and genotyped by utilizing the Sequenom MassARRAY system. Doppler sonography on the uterine arteries was performed at 20 weeks' gestation. Four polymorphisms in AGTR1 and AGTR2 genes, including AGTR1 A1166C, AGTR2 C4599A, AGTR2 A1675G and AGTR2 T1134C, were selected and significant associations were predominately observed for AGTR2 C4599A. When the cohort was stratified by maternal BMI, in women with BMI ≥ 25 kg/m(2), the AGTR2 C4599A AA genotype in mothers and neonates was associated with an increased risk for preecl sia compared with the CC genotype [adjusted OR 2.1 (95% CI 1.0-4.2) and adjusted OR 3.0 (95% CI 1.4-6.4), respectively]. In the same subset of women, paternal AGTR2 C4599A A allele was associated with an increased risk for preecl sia and uterine artery bilateral notching at 20 weeks' gestation compared with the C allele [adjusted OR 1.9 (95% CI 1.1-3.3) and adjusted OR 2.1 (95% CI 1.3-3.4), respectively]. AGTR2 C4599A in mothers, fathers and babies was associated with preecl sia and this association was only apparent in pregnancies in which the women had a BMI ≥ 25 kg/m(2), suggesting a gene-environment interaction.
External validation of prognostic models predicting pre-eclampsia: individual participant data meta-analysis
Publisher: Springer Science and Business Media LLC
Date: 02-11-2020
DOI: 10.1186/S12916-020-01766-9
Abstract: Pre-ecl sia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-ecl sia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-ecl sia using in idual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting. IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-ecl sia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-ecl sia as an outcome were included for validation. We reported the model predictive performance as discrimination ( C -statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis. Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C -statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model’s calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions appeared small and limited to probability thresholds between 5 and 7%. The evaluated models had modest predictive performance, with key limitations such as poor calibration (likely due to overfitting in the original development datasets), substantial heterogeneity, and small net benefit across settings. The evidence to support the use of these prediction models for pre-ecl sia in clinical decision-making is limited. Any models that we could not validate should be examined in terms of their predictive performance, net benefit, and heterogeneity across multiple UK settings before consideration for use in practice. PROSPERO ID: CRD42015029349 .
Complications of Pregnancy and Future Cardiovascular Risk
Publisher: Elsevier
Date: 2017
A systematic review of interventions to improve uptake of pertussis vaccination in pregnancy
Publisher: Public Library of Science (PLoS)
Date: 28-03-2019
Periconceptional nutrition and the relationship between maternal body weight changes in the periconceptional period and feto-placental growth in the sheep
Publisher: Wiley
Date: 05-2005
Hypoxia induced HIF-1/HIF-2 activity alters trophoblast transcriptional regulation and promotes invasion
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.EJCB.2015.10.004
Abstract: Reduced or absent cytotrophoblast invasion of the maternal uterine spiral arterioles is a common clinical finding in studies of pregnancies complicated by preecl sia, suggesting that the mechanisms mediating invasion of these cells is perturbed. The placenta initially develops in a low oxygen environment of 1-2% oxygen until after the 10th week of pregnancy. During this time oxygen concentration exerts a major influence over trophoblast activity and, hypoxia inducible factors are proposed to be one of many key regulators of first trimester trophoblast behaviour. We used a global gene expression microarray approach to identify signalling pathways and hypoxia-responsive genes of interest involved in invasion of the first trimester trophoblast cell line HTR8/SVneo under hypoxic conditions where HIF-1 was active. Additionally, first trimester placental s les from different gestational age groups were labelled with anti HIF-1α and HIF-2α to evaluate whether HIFs are differentially expressed and localised across two periods of placental development: (1) early first trimester characterised by hypoxia (6-8 weeks) and (2) late first trimester after initiation of maternal blood flow into the placenta (10-12 weeks). Invasion of HTR8/SVneo was assessed in real-time and was significantly increased in 1% compared with 5% and 21% oxygen and did not differ between 5% and 21% oxygen treatments. Eighty-eight genes were differentially expressed between cells cultured in 1% oxygen (where HIF-1α protein was localised to the nucleus) and 5% oxygen (where HIF-1α was mainly cytoplasmic). 65% of the genes were predicted to contain HIF-1α:HIF-1β transcription factor binding sites. While HIF-2α staining intensity in trophoblasts of late first trimester placenta was higher than early first trimester (+57%) the percentage of positively stained trophoblast nuclei did not differ between the two time points. There was no difference in the expression level of any of the hypoxia responsive genes of interest, IGFBP3, P4HA1, P4HA2, ANGPTL4 and MMP1 between early and late first trimester placenta. While HIF-1α and its downstream targets are clearly induced in HTR8/SVneo during in vitro hypoxic conditions, it appears that hypoxia inducible factors and genes are not altered throughout the first 7-12 weeks of placental development, during which the onset of maternal blood flow to the intervillous space takes place.
Responses to maternal GH or ractopamine during early-mid pregnancy are similar in primiparous and multiparous pregnant pigs
Publisher: Bioscientifica
Date: 03-08-2009
DOI: 10.1677/JOE-09-0131
Abstract: Fetal growth is restricted in primiparous pigs (gilts) compared with dams who have had previous pregnancies (sows), as in other species. In gilts, daily maternal porcine GH (pGH) injections from day 25 to 50 of pregnancy (term ∼115 day) increase fetal growth and progeny muscularity, and responses in sows are unknown. Whether feeding the β 2 -adrenergic agonist ractopamine during this period increases progeny growth rates in either parity and fetal responses in gilts, have not been investigated. We hypothesised that fetal and placental growth and fetal muscle development would be increased more by maternal pGH and/or ractopamine during early–mid pregnancy in gilts than sows, since fetal growth is restricted in gilts causing lower birth weights. Large White×Landrace gilts and sows were injected daily with water (controls) or pGH (∼15 μg/kg per day), or were fed 20 ppm ractopamine, between day 25 and 50 of pregnancy. Maternal pGH increased litter average fetal weight (11%, P =0.007) and length (3%, P =0.022), but not placental weight, at day 50 of pregnancy, irrespective of parity, and had the greatest effects in the heaviest fetuses of each litter. Maternal ractopamine increased average fetal weight (9%, P =0.018), but not length. Muscle fiber diameter was increased by pGH in heavy littermates and by ractopamine in median littermates. Similar fetal growth responses to pGH and ractopamine in gilts and sows suggest that these hormones increase fetal nutrient availability similarly in both parities. We therefore predict that sustained pGH treatment will increase progeny birth weight, postnatal growth and survival, in both sows and gilts.
Embryonic‐maternal cell interactions at implantation in the fat‐tailed dunnart, a dasyurid marsupial
Publisher: Wiley
Date: 09-1994
Abstract: In marsupials implantation occurs about two-thirds the way through the short gestation before which time the embryo is surrounded by the permeable shell membrane which prevents physical contact between the trophoblast and uterine epithelium. Although the trophoblast has been shown to be invasive to varying degrees in several species of marsupials, the ultrastructure of the embryonic-uterine cell interactions at the time of implantation has not been described in this group. Thick plastic sections and transmission electron microscopy were employed to investigate the cellular interactions at implantation in the fat-tailed dunnart (Sminthopsis crassicaudata), a dasyurid Australian marsupial. Our results show that epithelial penetration begins when the embryo is at the late presomite/early somite stage. In the trilaminar region of the yolk sac (TYS), trophoblast cells adjacent to the embryo form desmosomes with uterine epithelial cells and also appear to fuse with them to form hybrid cells, the cytoplasm of which resembles that of trophoblast. Later in the TYS, as the placenta develops, trophoblast microvilli and larger cell processes invaginate, and interdigitate with, the highly folded maternal epithelium but do not invade it. At this time in the bilaminar, or avascular, yolk sac (BYS), multinucleate trophoblast giant cells (TGCs) from an annular region adjacent to the sinus terminalis intrude between, and possibly fuse with, the maternal epithelium. The invading TGCs spread laterally above the residual basal lamina before migrating into the stroma. In this species of marsupial at least, the cell interactions at the time of implantation are similar to those seen in some eutherian species despite the fact that the fetal chorion is of yolk sac rather than allantoic origin.
Temporal placental genome wide expression profiles reflect three phases of utero-placental blood flow during early to mid human gestation
Publisher: Cold Spring Harbor Laboratory
Date: 28-06-2020
DOI: 10.1101/2020.06.25.20139709
Abstract: During early human placental development, extravillous cytotrophoblasts (EVT) invade the uterine vasculature to sequester a maternal blood supply. The impact of this on placental gene expression has not been established for normal pregnancy. Using RNA sequencing, we profiled placental chorionic villous tissues from 96 pregnancies at 6-23 weeks of gestation. We identified 1,048 genes that were differentially expressed between 6-10 weeks’ and 11-23 weeks’ of gestation. These are predominantly genes that are enriched in transcription factor signalling, inflammatory response and cell adhesion. Using a co-expression network and gene set enrichment analyses, we reveal three distinct phases of gene expression coincident with phases of maternal blood flow to the placenta that impact immune function and are likely driven by oxygen tension, potentially in a sex-specific manner. These data represent a comprehensive transcriptional profile of early placental development and point to significant environmental, genetic and regulatory triggers that drive gene expression.
Association between vitamin D status and hyperinsulinism
Publisher: Informa UK Limited
Date: 08-06-2019
Metabolic syndrome in pregnancy and risk for adverse pregnancy outcomes
Publisher: Public Library of Science (PLoS)
Date: 04-12-2018
GM-CSF regulates trophoblast glycogen cell and giant cell differentiation in placental morphogenesis
Publisher: Oxford University Press (OUP)
Date: 07-2009
Polymorphisms in the fibrinolytic pathway genes and the risk of recurrent spontaneous abortion
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.RBMO.2014.08.014
Abstract: Impaired fibrinolytic activity is implicated in the pathogenesis of recurrent spontaneous abortion (RSA). This case-control study assessed the prevalence of polymorphisms in fibrinolytic system genes in RSA. Cases comprised 202 Sinhalese women who had experienced at least two first-trimester spontaneous abortions and had no living children controls were 202 women with no history of spontaneous abortion and two or more living children. The groups were matched for age and ethnicity. DNA was genotyped using the Sequenom MassARRAY system. The PLAUR rs4251923 A (OR 95% CI 2.3 [1.3 to 4.0]), SERBP2 rs6098 A (OR 95% CI 1.4 [1.1 to 1.9]) and SERBP2 rs6103 C alleles (OR 95% CI 1.4 [1.1 to 1.9]) were increased in the RSA group compared with controls. The prevalence of PLAUR rs4251923/ SERBP2 rs6098/ SERBP2 rs6103 GG/AA/CC (OR 95% CI 2.4 [1.2 to 4.9], GA/GA/GC(OR 95% CI 3.9 [1.3 to 11.2]), GA/AA/CC (OR 95% CI 2.9 [1.0 to 8.6] and GA/GG/GG (OR 95% CI 21.3 [1.1 to 410.3]) genotypes were also increased in cases. Polymorphisms in the fibrinolytic system genes are associated with RSA in Sinhalese women. These likely impair implantation.
What are the experiences of supportive care in people affected by brain cancer and their informal caregivers: A qualitative systematic review
Publisher: Springer Science and Business Media LLC
Date: 31-05-2023
DOI: 10.1007/S11764-023-01401-5
Abstract: To critically synthesise qualitative research to understand experiences of supportive care in people affected by brain cancer and their informal caregivers. A qualitative systematic review was conducted according to the Joanna Briggs methodology and has been reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Guidelines. Electronic databases were searched by an expert systematic review librarian for all qualitative studies irrespective of research design. All publications were double screened by two reviewers using a pre-determined exclusion and inclusion criteria. The review was managed using Covidence systematic review software. Methodological quality assessment and data extraction were performed. Qualitative findings accompanied by illustrative quotes from included studies were extracted and grouped into categories, which created the overall synthesised findings. A total of 33 studies were included which represented a total s le of 671 participants inclusive of 303 patients and 368 informal caregivers. There was a total of 220 in idual findings included in this review, which were synthesised into two findings (1) caregivers and patients perceived supports which would have been helpful and (2) caregiver and patient experiences of unmet supportive care needs. This review highlighted the suffering and distress caused by brain cancer and associated treatments. Both patients and their informal caregivers experienced disconnect from themselves in renegotiating roles, and a profound sense of loneliness as the physical deterioration of the disease progressed. Both patients and informal caregivers reported similar unmet needs within the current service provision for brain cancer. However, what is apparent is that current cancer services are provided solely for patients, with little or no consideration to the support needs of both the patient and their informal caregiver. Service re-design is needed to improve care coordination with in idualised informational support, implementation of holistic needs assessments for both the patients and their caregivers, better community support provision, improved opportunities for emotional care with early referral for palliative care services. It is recommended that members of the multidisciplinary brain cancer team reflect on these findings to target holistic needs assessments and develop shared self-management care plans for both the patient and the informal caregiver.
3D ultrasound findings in women attending a South Australian recurrent miscarriage clinic
Publisher: Wiley
Date: 28-10-2016
DOI: 10.1002/AJUM.12032
Large-scale transcriptome-wide profiling of microRNAs in human placenta and maternal plasma at early to mid gestation
Publisher: Informa UK Limited
Date: 19-08-2021
Pregnancy, but not dietary octanoic acid supplementation, stimulates the ghrelin-pituitary growth hormone axis in mice
Publisher: Bioscientifica
Date: 05-2020
DOI: 10.1530/JOE-20-0072
Abstract: Circulating growth hormone (GH) concentrations increase during pregnancy in mice and remain pituitary-derived. Whether abundance or activation of the GH secretagogue ghrelin increase during pregnancy, or in response to dietary octanoic acid supplementation, is unclear. We therefore measured circulating GH profiles in late pregnant C57BL/6J mice and in aged-matched non-pregnant females fed with standard laboratory chow supplemented with 5% octanoic or palmitic (control) acid ( n = 4–13/group). Serum total and acyl-ghrelin concentrations, stomach and placenta ghrelin mRNA and protein expression, Pcsk1 (encoding prohormone convertase 1/3) and Mboat4 (membrane bound O-acyl transferase 4) mRNA were determined at zeitgeber (ZT) 13 and ZT23. Total and basal GH secretion were higher in late pregnant than non-pregnant mice ( P 0.001), regardless of diet. At ZT13, serum concentrations of total ghrelin ( P = 0.004), but not acyl-ghrelin, and the density of ghrelin-positive cells in the gastric antrum ( P = 0.019) were higher, and gastric Mboat4 and Pcsk1 mRNA expression were lower in pregnant than non-pregnant mice at ZT23. In the placenta, ghrelin protein was localised mostly to labyrinthine trophoblast cells. Serum acyl-, but not total, ghrelin was lower at mid-pregnancy than in non-pregnant mice, but not different at early or late pregnancy. In conclusion, dietary supplementation with 5% octanoic acid did not increase activation of ghrelin in female mice. Our results further suggest that increases in maternal GH secretion throughout murine pregnancy are not due to circulating acyl-ghrelin acting at the pituitary. Nevertheless, time-dependent increased circulating total ghrelin could potentially increase ghrelin action in tissues that express the acylating enzyme and receptor.
Fetal sex and the circulating renin- angiotensin system during early gestation in women who later develop preeclampsia or gestational hypertension
Publisher: Springer Science and Business Media LLC
Date: 20-06-2013
DOI: 10.1038/JHH.2013.51
Abstract: There are fetal sex-specific differences in the balance between angiotensin (Ang) II and Ang-(1-7) in the maternal circulation during pregnancy. To determine whether at 15 weeks' gestation plasma levels of Ang II and Ang-(1-7), as well as levels of prorenin and Ang-converting enzyme (ACE), predicted the development of gestational hypertension (GH) or preecl sia (PreE) and were associated with estimates of fetal and maternal health, women who later developed GH (n=50) or PreE (n=50) were compared with body mass index-matched controls (n=100). Women who subsequently developed PreE or GH had increased Ang-(1-7) levels at 15 weeks' gestation compared with women with normal pregnancies. When separated by fetal sex, this difference was seen only in women carrying a female fetus. Prorenin and ACE concentrations were not useful biomarkers for the prediction of either PreE or GH at 15 weeks' gestation. Women with a male fetus who developed PreE and women who subsequently developed GH had increased blood pressures at 15 weeks' gestation compared with women with normal pregnancies, suggesting that these women were on an early trajectory for the development of hypertension. We propose that measurement of Ang-(1-7) during early gestation could be useful in predicting, those women who will go on to develop new-onset hypertension in pregnancy.
The deleterious effects of cannabis during pregnancy on neonatal outcomes
Publisher: AMPCo
Date: 25-05-2020
DOI: 10.5694/MJA2.50624
External validation of prognostic models to predict stillbirth using International Prediction of Pregnancy Complications (IPPIC ) Network database: individual participant data meta‐analysis
Publisher: Wiley
Date: 02-2022
DOI: 10.1002/UOG.23757
Abstract: Stillbirth is a potentially preventable complication of pregnancy. Identifying women at high risk of stillbirth can guide decisions on the need for closer surveillance and timing of delivery in order to prevent fetal death. Prognostic models have been developed to predict the risk of stillbirth, but none has yet been validated externally. In this study, we externally validated published prediction models for stillbirth using in idual participant data (IPD) meta‐analysis to assess their predictive performance. MEDLINE, EMBASE, DH‐DATA and AMED databases were searched from inception to December 2020 to identify studies reporting stillbirth prediction models. Studies that developed or updated prediction models for stillbirth for use at any time during pregnancy were included. IPD from cohorts within the International Prediction of Pregnancy Complications (IPPIC) Network were used to validate externally the identified prediction models whose in idual variables were available in the IPD. The risk of bias of the models and cohorts was assessed using the Prediction study Risk Of Bias ASsessment Tool (PROBAST). The discriminative performance of the models was evaluated using the C ‐statistic, and calibration was assessed using calibration plots, calibration slope and calibration‐in‐the‐large. Performance measures were estimated separately in each cohort, as well as summarized across cohorts using random‐effects meta‐analysis. Clinical utility was assessed using net benefit. Seventeen studies reporting the development of 40 prognostic models for stillbirth were identified. None of the models had been previously validated externally, and the full model equation was reported for only one‐fifth (20%, 8/40) of the models. External validation was possible for three of these models, using IPD from 19 cohorts (491 201 pregnant women) within the IPPIC Network database. Based on evaluation of the model development studies, all three models had an overall high risk of bias, according to PROBAST. In the IPD meta‐analysis, the models had summary C ‐statistics ranging from 0.53 to 0.65 and summary calibration slopes ranging from 0.40 to 0.88, with risk predictions that were generally too extreme compared with the observed risks. The models had little to no clinical utility, as assessed by net benefit. However, there remained uncertainty in the performance of some models due to small available s le sizes. The three validated stillbirth prediction models showed generally poor and uncertain predictive performance in new data, with limited evidence to support their clinical application. The findings suggest methodological shortcomings in their development, including overfitting. Further research is needed to further validate these and other models, identify stronger prognostic factors and develop more robust prediction models. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
The interaction between metabolic syndrome and physical activity, and risk for gestational diabetes mellitus
Publisher: Springer Science and Business Media LLC
Date: 20-03-2021
Placental Inflammasome mRNA Levels Differ by Mode of Delivery and Fetal Sex
Publisher: Frontiers Media SA
Date: 25-03-2022
DOI: 10.3389/FIMMU.2022.807750
Abstract: Parturition signals the end of immune tolerance in pregnancy. Term labour is usually a sterile inflammatory process triggered by damage associated molecular patterns (DAMPs) as a consequence of functional progesterone withdrawal. Activation of DAMPs recruits leukocytes and inflammatory cytokine responses in the myometrium, decidua, cervix and fetal membranes. Emerging evidence shows components of the inflammasome are detectable in both maternal decidua and placenta. However, the activation of the placental inflammasome with respect to mode of delivery has not been profiled. Placental chorionic villus s les from women delivering at term via unassisted vaginal (UV) birth, labouring lower segment caesarean section (LLSCS, emergency caesarean section) and prelabour lower segment caesarean section (PLSCS, elective caesarean section) underwent high throughput RNA sequencing (NextSeq Illumina) and bioinformatic analyses to identify differentially expressed inflammatory (DE) genes. DE genes ( IL1RL1 , STAT1 , STAT2 , IL2RB , IL17RE , IL18BP , TNFAIP2 , TNFSF10 and TNFRSF8 ), as well as common inflammasome genes ( IL1B , IL1R1 , IL1R2 , IL6 , IL18 , IL18R1 , IL18R1 , IL10 , and IL33 ), were targets for further qPCR analyses and Western blotting to quantify protein expression. There was no specific sensor molecule-activated inflammasome which dominated expression when stratified by mode of delivery, implying that multiple inflammasomes may function synergistically during parturition. Whilst placentae from women who had UV births overall expressed pro-inflammatory mediators, placentae from LLSCS births demonstrated a much greater pro-inflammatory response, with additional interplay of pro- and anti-inflammatory mediators. As expected, inflammasome activation was very low in placentae from women who had PLSCS births. Sex-specific differences were also detected. Placentae from male-bearing pregnancies displayed higher inflammasome activation in LLSCS compared with PLSCS, and placentae from female-bearing pregnancies displayed higher inflammasome activation in LLSCS compared with UV. In conclusion, placental inflammasome activation differs with respect to mode of delivery and neonatal sex. Its assessment may identify babies who have been exposed to aberrant inflammation at birth that may compromise their development and long-term health and wellbeing.
Folic acid supplementation is associated with size at birth in the Screening for Pregnancy Endpoints (SCOPE) international prospective cohort study
Publisher: Elsevier BV
Date: 08-2020
A novel embryo culture media supplement that improves pregnancy rates in mice
Publisher: Bioscientifica
Date: 03-2017
DOI: 10.1530/REP-16-0517
Abstract: The preimplantation embryo in vivo is exposed to numerous growth factors in the female reproductive tract, which are not recapitulated in embryo culture media in vitro . The IGF2 and plasminogen activator systems facilitate blastocyst development. We hypothesized that the addition of IGF2 in combination with urokinase plasminogen activator (uPA) and plasminogen could improve rates of blastocyst hatching and implantation in mice. B6BcF1 and CBAB6F2 mouse embryos were ided into one of four supplemented culture media treatment groups: (1) control (media only) (2) 12.5 nM IGF2 (3) 10 µg/mL uPA and 5 µg/mL plasminogen or (4) a combination of IGF2, uPA and plasminogen treatments. Embryo development to blastocyst stage and hatching were assessed before transfer to pseudopregnant recipient females and implantation, pregnancy rates and postnatal growth were assessed. After 90.5 h of culture, IGF2 + U + P treatment increased the percentage of B6BcF1 embryos that were hatching/hatched and percentage developing to blastocyst stage compared with controls ( P 0.02). Following B6BcF1 embryo transfer, IGF2 + U + P treatment increased implantation sites at day 8 of pregnancy compared with controls ( P 0.05). Replication in the CBAB6F2 mouse strain showed significant improvements in pregnancy rates at days 8 and 18 but not in blastocyst development. No adverse effects were seen on gestational age, litter size or birthweight, or the reproductive capacity of offspring of IGF2 + U + P treated embryos. For embryos susceptible to detrimental effects of in vitro culture, IGF2, uPA and plasminogen supplementation of culture media can improve pregnancy success, but the effect of treatment is dependent on the mouse strain.
Duration of sexual relationship and its effect on preeclampsia and small for gestational age perinatal outcome
Publisher: Elsevier BV
Date: 10-2009
DOI: 10.1016/J.JRI.2009.04.011
Abstract: The aim of this study was to determine if women with preecl sia or delivering small for gestational age (SGA) babies are more likely to have a short duration of sexual relationship compared with those who have uncomplicated pregnancies. In a prospective cohort study, 2507 nulliparous women with singleton pregnancies were interviewed at 15+/-1 weeks gestation about the duration of their sexual relationship with the biological father. Short duration of sexual relationship (< or =6 months, < or =3 months, or first intercourse) was compared between women with preecl sia (N=131) or SGA babies (N=263) and those with uncomplicated pregnancies (N=1462). Short duration of sexual relationship was more common in women with preecl sia compared with uncomplicated pregnancies (< or =6 months 14.5% versus 6.9%, adjusted odds ratio [adjOR] 1.88, 95% CI 1.05-3.36 < or =3 months 6.9% versus 2.5%, adjOR 2.32, 95% CI 1.03-5.25 first intercourse 1.5% versus 0.5%, adjOR 5.75, 95% CI 1.13-29.3). Although the total number of semen exposures was lower in SGA, SGA was not associated with a shorter duration of sexual relationship. On post hoc analysis, the subgroup of SGA with abnormal uterine artery Doppler at 20 weeks (N=58) were more likely to have had a short sexual relationship compared with controls (< or =6 months adjOR 2.33, 95% CI 1.09-4.98 < or =3 months adjOR 3.22, 95% CI 1.18-8.79 first intercourse adjOR 8.02, 95% CI 1.58-40.7). We conclude that compared to uncomplicated pregnancies, short duration of sexual relationship is more common in women who develop preecl sia and women with abnormal uterine artery Doppler waveforms who deliver an SGA baby.
Epigenetics and Imprinting of the Trophoblast – A Workshop Report
Publisher: Elsevier BV
Date: 04-2006
DOI: 10.1016/J.PLACENTA.2006.01.015
Abstract: Genomic imprinting is a remarkable process that causes genes to be expressed or repressed depending on their parental-origin. Imprinted genes play important roles in prenatal growth and organ development. Postnatally, imprinted genes can contribute to the regulation of metabolic pathways and behaviour associated with the control of resources. One of the most important sites of imprinted gene action is the placenta. During this workshop at the 11th meeting of the International Federation of Placenta Associations/European Placenta Group held in Glasgow, a series of short talks were presented providing an overview of the evolution, function and mechanisms of imprinting in mammals with particular reference to the placenta. In addition, epigenetic control of trophoblast development and function were considered. This report summarises the contributions to the workshop.
The association of maternal ACE A11860G with small for gestational age babies is modulated by the environment and by fetal sex: Amulticentrex prospective case-control study
Publisher: Oxford University Press (OUP)
Date: 23-04-2013
IFPA meeting 2014 workshop report: Animal models to study pregnancy pathologies; new approaches to study human placental exposure to xenobiotics; biomarkers of pregnancy pathologies; placental genetic
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.PLACENTA.2015.01.196
Abstract: Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2014 there were six themed workshops, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of animal models, xenobiotics, pathological biomarkers, genetics and epigenetics, and stillbirth and fetal growth restriction.
Tiered Prediction System for Preeclampsia: an integrative application of multiple models
Publisher: Modelling and Simulation Society of Australia and New Zealand (MSSANZ), Inc.
Date: 12-2013
Effectiveness of birthing kits for clean childbirth
Publisher: Oxford University Press (OUP)
Date: 24-07-2020
Abstract: Poor infection control practices during childbirth are recognised as a critical factor leading to life-threatening maternal and newborn sepsis. Therefore, this paper assesses the effectiveness of clean birth kits (CBKs) to ensure a safe birthing environment. We searched PubMed, Cochrane Library and CINAHL, as well as Google Scholar, to identify both qualitative and quantitative studies on CBKs published in English up to November 2018. Studies were included if the pregnant women or women giving birth intended to use or used a CBK. The methodological quality of included papers was assessed. A total of 37 studies, 26 quantitative and 11 qualitative studies, were included. Quantitative studies showed a positive impact of CBKs on reducing the incidence of puerperal sepsis and neonatal tetanus. The review also identified CBK use to be associated with a reduction in perinatal, neonatal and young infant mortality. Qualitative studies suggested that a lack of awareness of the importance of CBKs and clean delivery practices, unavailability of CBKs and financial constraints to purchase CBKs were the potential barriers. CBKs appear to be a promising strategy to reduce maternal and neonatal morbidity and mortality. However, the current evidence is limited and further large-scale trials are required.
Placentation in the dasyurid marsupial, Sminthopsis crassicaudata, the fat-tailed dunnart, and notes on placentation of the didelphid Monodelphis domestica
Publisher: Bioscientifica
Date: 1994
Abstract: A light microscope study of the choriovitelline (yolk sac) placenta of the dasyurid marsupial, Sminthopsis crassicaudata, and some comparative observations on that of the didelphid, Monodelphis domestica, were performed. In the former species, the placenta was composed of an invasive bilaminar, avascular, yolk sac and a non-invasive trilaminar, vascular yolk sac. The bilaminar yolk sac placenta had trophoblast giant cells that eroded the maternal epithelium, but there was no evidence of invasion of maternal capillaries thus, an endotheliochorial placenta was present. In the trilaminar yolk sac placenta, the convoluted chorion followed the contours of the highly folded endometrial epithelium but did not erode it and, therefore, an epitheliochorial placenta was formed. In late pregnancy, the choriovitelline placenta of Monodelphis domestica also had two regions, but the fetal trophoblast did not invade the uterine epithelium in either region. Rather, there were discontinuous areas of adhesion between trophoblast giant cells and uterine epithelium in the trilaminar yolk sac placenta and some extensive areas of adhesion in the attenuated bilaminar yolk sac placenta. The yolk sac placenta in M. domestica, unlike that of S. crassicaudata, therefore appears to be epitheliochorial in the vascular and non-vascular regions.
Reduced Dietary Calcium and Vitamin D Results in Preterm Birth and Altered Placental Morphogenesis in Mice During Pregnancy
Publisher: Springer Science and Business Media LLC
Date: 2020
Off to the right start: How pregnancy and early life can determine future animal health and production
Publisher: CSIRO Publishing
Date: 2018
DOI: 10.1071/AN17014
Abstract: Animal producers are well aware that a low-birthweight animal is more likely to die in the first few days of life, and, if it survives, it is likely to perform poorly. We are now coming to appreciate that early life events can permanently change an animal’s developmental trajectory, also often referred to as developmental programming. This is an area of current interest in biomedicine, where the concept is known as the ‘developmental origins of health and disease’ (DOHaD). Current gaps in understanding include many of the underlying mechanisms, and whether and how we might intervene and restore the potential for healthy and productive development. This review introduces the biomedical perspective of developmental programming, reviews some of the evidence for long-term effects of early life exposures on welfare and productivity in animal production, with a focus on prenatal growth and maternal stress in pig production, and discusses options for intervening to improve long-term outcomes.
Viperin is an important host restriction factor in control of Zika virus infection
Publisher: Springer Science and Business Media LLC
Date: 30-06-2017
DOI: 10.1038/S41598-017-04138-1
Abstract: Zika virus (ZIKV) infection has emerged as a global health threat and infection of pregnant women causes intrauterine growth restriction, spontaneous abortion and microcephaly in newborns. Here we show using biologically relevant cells of neural and placental origin that following ZIKV infection, there is attenuation of the cellular innate response characterised by reduced expression of IFN-β and associated interferon stimulated genes (ISGs). One such ISG is viperin that has well documented antiviral activity against a wide range of viruses. Expression of viperin in cultured cells resulted in significant impairment of ZIKV replication, while MEFs derived from CRISPR/Cas9 derived viperin −/− mice replicated ZIKV to higher titers compared to their WT counterparts. These results suggest that ZIKV can attenuate ISG expression to avoid the cellular antiviral innate response, thus allowing the virus to replicate unchecked. Moreover, we have identified that the ISG viperin has significant anti-ZIKV activity. Further understanding of how ZIKV perturbs the ISG response and the molecular mechanisms utilised by viperin to suppress ZIKV replication will aid in our understanding of ZIKV biology, pathogenesis and possible design of novel antiviral strategies.
Factors influencing RNA yield from placenta tissue
Publisher: Elsevier BV
Date: 09-2023
Early pregnancy maternal endocrine insulin-like growth factor I programs the placenta for increased functional capacity throughout gestation
Publisher: The Endocrine Society
Date: 09-2007
DOI: 10.1210/EN.2007-0411
Abstract: In early pregnancy, the concentrations of IGFs increase in maternal blood. Treatment of pregnant guinea pigs with IGFs in early to midpregnancy enhances placental glucose transport and fetal growth and viability near term. In the current study, we determined whether exogenous IGFs altered placental gene expression, transport, and nutrient partitioning during treatment, which may then persist. Guinea pigs were infused with IGF-I, IGF-II (both 1 mg/kg·d) or vehicle sc from d 20–35 of pregnancy and killed on d 35 (term is 70 d) after administration of [3H]methyl-d-glucose (MG) and [14C]amino-isobutyric acid (AIB). IGF-I increased placental and fetal weights (+15 and +17%, respectively) and MG and AIB uptake by the placenta (+42 and +68%, respectively) and fetus (+59 and +90%, respectively). IGF-I increased placental mRNA expression of the amino acid transporter gene Slc38a2 (+780%) and reduced that of Igf2 (−51%), without altering the glucose transporter Slc2a1 or Vegf and Igf1 genes. There were modest effects of IGF-I treatment on MG and AIB uptake by in idual maternal tissues and no effect on plasma glucose, total amino acids, free fatty acids, triglycerides, and cholesterol concentrations. IGF-II treatment of the mother did not alter any maternal, fetal or placental parameter. In conclusion, exogenous IGF-I, but not IGF-II, in early pregnancy increases placental transport of MG and AIB, enhancing midgestational fetal nutrient uptake and growth. This suggests that early pregnancy rises in maternal circulating IGF-I play a major role in regulating placental growth and functional development and thus fetal growth throughout gestation.
Effectiveness of a nurse practitioner-led cardiovascular prevention clinic at reduction of metabolic syndrome following maternal complications of pregnancy: a preliminary analysis
Publisher: Springer Science and Business Media LLC
Date: 06-10-2022
DOI: 10.1186/S13098-022-00916-8
Abstract: Maternal complications of pregnancy, including hypertensive disorders of pregnancy, gestational diabetes mellitus, intrauterine growth restriction, preterm labour, and placental abruption, are associated with increased risk of future cardiometabolic disease. Lifestyle interventions that focus on preventative strategies for this young, high-risk population of women may assist in cardiometabolic disease risk reduction. The aim of this preliminary registry analysis was to observe the change in maternal metabolic syndrome status after receiving a nurse practitioner-led lifestyle intervention delivered soon after a complicated pregnancy. This preliminary analysis included 64 eligible women who had attended both baseline (approximately 6 months postpartum) and review (approximately eighteen months postpartum) appointments at the postpartum lifestyle clinic after an index pregnancy complicated by at least one maternal complication of pregnancy. Metabolic syndrome status at both appointments was assessed. At the baseline appointment, 22 (34.4%) women met the criteria for metabolic syndrome. This number reduced at the review appointment to 19 (29.7%). This difference was not statistically significant. There were some modest improvements in the in idual cardiometabolic risk factors, as well as marked improvements in the women who had recovered from metabolic syndrome over twelve months. There was a high percentage of metabolic syndrome present early in the postpartum period. The results of this preliminary analysis highlight the importance of continuing preventative care and ongoing research for this group of high-risk women.
Asthma treatment impacts time to pregnancy
Publisher: European Respiratory Society (ERS)
Date: 02-2018
Chronic maternal feed restriction impairs growth but increases adiposity of the fetal guinea pig
Publisher: American Physiological Society
Date: 2005
DOI: 10.1152/AJPREGU.00360.2004
Abstract: Small size at birth has been associated with an increased risk of central obesity and reduced lean body mass in adult life. This study investigated the time of onset of prenatally induced obesity, which occurs after maternal feed restriction, in the guinea pig, a species that, like the human, develops substantial adipose tissue stores before birth. We examined the effect of maternal feed restriction [70% ad libitum intake from 4 wk before to midpregnancy, then 90% until day 60 gestation (term ∼69 days)] on fetal growth and body composition in the guinea pig. Maternal feed restriction reduced fetal (−39%) and placental (−30%) weight at 60 days gestation and reduced liver, biceps muscle, spleen, and thymus weights, relative to fetal weight, while relative weights of brain, lungs, and interscapular and retroperitoneal fat pads were increased. In the interscapular depot, maternal feed restriction decreased the volume density of multilocular fat and increased that of unilocular fat, resulting in an increased relative weight of interscapular unilocular fat. Maternal feed restriction did not alter the relative weight of perirenal fat or the volume density of adipocyte populations within the depot but increased unilocular lipid locule size. Maternal feed restriction in the guinea pig is associated with decreased weight of major organs, including liver and skeletal muscle, but increased adiposity of the fetus, with relative sparing of unilocular adipose tissue. If this early-onset obesity persists, it may contribute to the metabolic and cardiovascular dysfunction that these offspring of feed-restricted mothers develop as adults.
Early restriction of placental growth results in placental structural and gene expression changes in late gestation independent of fetal hypoxemia
Publisher: Wiley
Date: 12-2016
DOI: 10.14814/PHY2.13049
Characterization of 5-methylcytosine and 5-hydroxymethylcytosine in human placenta cell types across gestation
Publisher: Informa UK Limited
Date: 30-04-2019
Folate, Vitamin B12, Vitamin B6 and homocysteine: Impact on pregnancy outcome
Publisher: Wiley
Date: 24-10-2013
Epigenetic risks related to assisted reproductive technologies: Short- and long-term consequences for the health of children conceived through assisted reproduction technology: more reason for caution
Publisher: Oxford University Press (OUP)
Date: 11-2002
DOI: 10.1093/HUMREP/17.11.2783
Abstract: Does the manipulation of gametes and embryos as practised in human IVF invoke perturbations in fetal and neonatal phenotype? There is increasing evidence that the answer is 'yes', although the degree of perturbation may be less acute than observed in other species. However, the long-term consequences are not known, and may prove to be considerable. There is now a substantial body of evidence from animal models suggesting that assisted reproductive technologies (ART) are associated with altered outcomes in fetal and neonatal development. Epigenetic modification of gene expression is an attractive hypothesis that accounts for these differences and is one of a number of causal pathways that may be activated by cellular stress invoked during manipulation. Here we widen the debate to propose that environment-induced cellular stress also acts to modify fetal and placental gene expression, potentially also contributing to phenotype skewing after ART.
The metabolic syndrome in pregnancy and its association with child telomere length
Publisher: Springer Science and Business Media LLC
Date: 29-07-2020
Distinct Patterns of Gene-Specific Methylation in Mammalian Placentas: Implications for Placental Evolution and Function
Publisher: Elsevier BV
Date: 04-2010
DOI: 10.1016/J.PLACENTA.2010.01.009
Abstract: The placenta has arisen relatively recently and is among the most rapidly evolving tissues in mammals. Several different placental barrier and structure types appear to have independently evolved common functional features. Specific patterns of gene expression that determine placental development in humans are predicted to be accompanied by specific profiles of epigenetic modification. However, the stratification of epigenetic modifications into those involved in conserved aspects of placental function, versus those involved in ergent placental features, has yet to begin. As a first step towards this goal, we have investigated the methylation status of a small number of gene-specific methylation events recently identified in human placenta, in a panel of placental tissue from baboon, marmoset, cow, cat, guinea pig and mouse. These represent disparate placental barrier types and structures. In this study we hypothesized that specific epigenetic markings may be associated with placental barrier type or function, independent of phylogeny. However, in contrast to our predictions, the majority of gene-specific methylation appears to track with phylogeny, independent of placental barrier type or other structural features. This suggests that despite the likelihood of epigenetic modification playing a role in the functioning and evolution of different placental subtypes, there is no evidence for an involvement of the gene-specific methylation profiles we have identified, in specifying these differences. Further studies, examining larger numbers of epigenetic modifications across phylogeny, are required to define the role of specific epigenetic modifications in the evolution of distinct placental structures.
The INSR rs2059806 single nucleotide polymorphism, a genetic risk factor for vascular and metabolic disease, associates with pre-eclampsia
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.RBMO.2017.01.001
Abstract: Pre-ecl sia is a risk factor for later life vascular and metabolic diseases. This study postulates that this reflects a common genetic cause, and investigates whether the INSR rs2059806 single nucleotide polymorphism (SNP) (a risk factor for essential hypertension, type 2 diabetes and metabolic syndrome) is also associated with pre-ecl sia. The association of INSR rs2059806 with pre-ecl sia was tested in two cohorts - a Caucasian case control group (123 pre-ecl tic mother-father-baby trios and 1185 mother-father-baby trios from uncomplicated pregnancies) and an independent cohort of Sinhalese women (175 women with pre-ecl sia and 171 women with uncomplicated pregnancies). In the Caucasian cohort, the prevalence of the INSR rs2059806 AA genotype was greater among pre-ecl tic women compared with the uncomplicated pregnancies (12.7% versus 4.7%, OR[95%CI] = 3.1[1.6-5.8], P = 0.0003). In the Sinhalese cohort, maternal INSR rs2059806 AA genotype was greater among pre-ecl tic women who delivered small for gestational age infants compared with the uncomplicated pregnancies (10.8% versus 4.2%, OR[95%CI] = 2.8[1.0-7.4], P = 0.03). Thus, it was found that the INSR rs2059806 SNP is also associated with pre-ecl sia phenotypes in two independent cohorts suggesting that genetic susceptibility may be implicated in the link between pre-ecl sia and subsequent vascular and metabolic diseases.
Effect of selenium and iodine on oxidative stress in the first trimester human placenta explants
Publisher: MDPI AG
Date: 28-02-2021
DOI: 10.3390/NU13030800
Abstract: Imbalanced maternal micronutrient status, poor placentation, and oxidative stress are associated with greater risk of pregnancy complications, which impact mother and offspring health. As selenium, iodine, and copper are essential micronutrients with key roles in antioxidant systems, this study investigated their potential protective effects on placenta against oxidative stress. First trimester human placenta explants were treated with different concentrations of selenium (sodium selenite), iodine (potassium iodide), their combination or copper (copper (II) sulfate). The concentrations represented deficient, physiological, or super physiological levels. Oxidative stress was induced by menadione or antimycin. Placenta explants were collected, fixed, processed, and embedded for laser ablation inductively coupled plasma-mass spectrometry (LA ICP-MS) element imaging or immunohistochemical labelling. LA ICP-MS showed that placenta could uptake selenium and copper from the media. Sodium selenite and potassium iodide reduced DNA damage and apoptosis (p 0.05). Following oxidative stress induction, a higher concentration of sodium selenite (1.6 µM) was needed to reduce DNA damage and apoptosis while both concentrations of potassium iodide (0.5 and 1 µM) were protective (p 0.05). A high concentration of copper (40 µM) increased apoptosis and DNA damage but this effect was no longer significant after induction of oxidative stress. Micronutrients supplementation can increase their content within the placenta and an optimal maternal micronutrient level is essential for placenta health.
Insulin family polymorphisms in pregnancies complicated by small for gestational age infants
Publisher: Oxford University Press (OUP)
Date: 18-06-2015
Abstract: Being born small for gestational age (SGA) increases the risk for adverse perinatal outcomes and later life vascular and metabolic disorders. The insulin family plays a vital role in intrauterine growth. We investigated the association of functional SNPs in insulin (INS), insulin receptor (INSR) and insulin receptor substrate 2 (IRS2) with small for gestational age (SGA) pregnancies, uterine and umbilical artery Doppler and plasma insulin level. We conducted a nested case-control study of 1401 nulliparous Caucasian women, their partners and babies (216 SGA and 1185 uncomplicated). SGA was defined as a birthweight less than the 10th customized birthweight percentile adjusted for maternal height, weight, parity, ethnicity, gestational age at delivery and infant sex. Uterine and umbilical artery Doppler was performed at 20 ± 1 week gestation. The SNPs in the parent infant trios were genotyped using Sequenom MassARRAY. Plasma insulin was measured by double antibody RIA in 188 healthy non-pregnant adults to assess correlations between SNP genotypes and circulating insulin. Paternal [odds ratio (OR) (95% CI) = 2.2 (1.3-3.9), P = 0.005] and infant [OR (95% CI) = 3.3 (1.7-6.2), P = 0.0001] INSR rs2059806 AA genotype was associated with SGA. Infant INSR rs2059806 A allele was associated with abnormal umbilical artery Doppler [OR (95% CI) = 1.3(1.0-1.7), P = 0.04]. INSR rs2059806 AA homozygous in iduals had lower plasma insulin compared with heterozygotes (P = 0.03) and GG homozygotes (P = 0.03). The INSR rs2059806 SNP previously associated with adult vascular and metabolic diseases is also associated with SGA pregnancies. This polymorphism may associate with the risk of vascular and metabolic disorders across the life course.
Impact of glucose infusion on the structural and functional characteristics of adipose tissue and on hypothalamic gene expression for appetite regulatory neuropeptides in the sheep fetus during late g
Publisher: Wiley
Date: 05-2005
Circulating IGF1 and IGF2 and SNP genotypes in men and pregnant and non-pregnant women
Publisher: Bioscientifica
Date: 09-2014
DOI: 10.1530/EC-14-0068
Abstract: Circulating IGFs are important regulators of prenatal and postnatal growth, and of metabolism and pregnancy, and change with sex, age and pregnancy. Single-nucleotide polymorphisms (SNPs) in genes coding for these hormones associate with circulating abundance of IGF1 and IGF2 in non-pregnant adults and children, but whether this occurs in pregnancy is unknown. We therefore investigated associations of plasma IGF1 and IGF2 with age and genotype at candidate SNPs previously associated with circulating IGF1, IGF2 or methylation of the INS – IGF2 – H19 locus in men ( n =134), non-pregnant women ( n =74) and women at 15 weeks of gestation ( n =98). Plasma IGF1 concentrations decreased with age ( P .001) and plasma IGF1 and IGF2 concentrations were lower in pregnant women than in non-pregnant women or men (each P .001). SNP genotypes in the INS – IGF2 – H19 locus were associated with plasma IGF1 ( IGF2 rs680, IGF2 rs1004446 and IGF2 rs3741204) and IGF2 ( IGF2 rs1004446, IGF2 rs3741204 and H19 rs217727). In single SNP models, effects of IGF2 rs680 were similar between groups, with higher plasma IGF1 concentrations in in iduals with the GG genotype when compared with GA ( P =0.016), or combined GA and AA genotypes ( P =0.003). SNPs in the IGF2 gene associated with IGF1 or IGF2 were in linkage disequilibrium, hence these associations could reflect other genotype variations within this region or be due to changes in INS – IGF2 – H19 methylation previously associated with some of these variants. As IGF1 in early pregnancy promotes placental differentiation and function, lower IGF1 concentrations in pregnant women carrying IGF2 rs680 A alleles may affect placental development and/or risk of pregnancy complications.
Prediction of Small for Gestational Age Infants in Healthy Nulliparous Women Using Clinical and Ultrasound Risk Factors Combined with Early Pregnancy Biomarkers
Publisher: Public Library of Science (PLoS)
Date: 09-01-2017
Seasonality of gestational diabetes mellitus: A South Australian population study
Publisher: BMJ
Date: 10-2016
Gastrointestinal Adenocarcinoma Incidence and Survival Trends in South Australia, 1990–2017
Publisher: MDPI AG
Date: 06-01-2022
Abstract: Background & Aims: Globally, there has been a concerning rise in the incidence of young-onset cancers. The aim of this study was to provide trends in the incidence and survival of gastrointestinal adenocarcinomas (oesophagus, stomach, pancreas, and colorectal) in South Australia over a 27-year period. Methods: This is a cross-sectional analysis of a prospective longitudinal database including all cases of gastrointestinal adenocarcinomas prospectively reported to the South Australian (State) Cancer Registry from 1990 to 2017. Results: A total of 28,566 patients diagnosed with oesophageal, stomach, pancreatic, or colorectal adenocarcinoma between 1990 and 2017 were included in the study. While the overall incidence for gastrointestinal adenocarcinomas in in iduals years has decreased since 2000 (IRR of 0.97 (95% CI 0.94–1.00 p = 0.06)) compared to 1990–1999, the rate amongst in iduals aged 18–50 has significantly increased (IRR 1.41 (95% CI 1.27–1.57 p 0.001)) during the same reference time period. Although noted in both sexes, the rate of increase in incidence was significantly greater in males (11.5 to 19.7/100,000 p 0.001). The overall survival from adenocarcinomas across all subsites improved in the -year cohort in the last decade (HR 0.89 (95% CI 0.86–0.93 p 0.001)) compared to 1990–1999. In in iduals aged 18–50 years, there has only been a significant improvement in survival for colorectal cancer (HR 0.82 (95% CI 0.68–0.99 p 0.04)), but not the other subsites. A lower overall survival was noted for males in both age cohorts (18–50 years—HR 1.24 (95% CI 1.09–1.13 p 0.01) and years—HR 1.13 (95% CI 1.10–1.16 p 0.001), respectively) compared to females. Conclusions: This study from South Australia demonstrates a significant increase in young-onset gastrointestinal adenocarcinomas over the last 28 years, with a greater increase in the male sex. The only significant improvement in survival in this cohort has been noted in colorectal cancer patients.
Association between maternal zinc status, dietary zinc intake and pregnancy complications: A systematic review
Publisher: MDPI AG
Date: 15-10-2016
DOI: 10.3390/NU8100641
Placental adaptations in growth restriction
Publisher: MDPI AG
Date: 08-01-2015
DOI: 10.3390/NU7010360
Premature lambs grown in a bag
Publisher: Springer Science and Business Media LLC
Date: 06-2017
DOI: 10.1038/546045A
Psychosocial determinants of pertussis and influenza vaccine uptake in pregnant women: A prospective study
Publisher: Elsevier BV
Date: 04-2020
Agreement of aneroid and oscillometric blood pressure devices used in pregnancy
Publisher: Elsevier BV
Date: 07-2019
Metabolic Profiling Uncovers a Phenotypic Signature of Small for Gestational Age in Early Pregnancy
Publisher: American Chemical Society (ACS)
Date: 29-06-2011
DOI: 10.1021/PR2002897
Abstract: Being born small for gestational age (SGA) confers increased risks of perinatal morbidity and mortality and increases the risk of cardiovascular complications and diabetes in later life. Accumulating evidence suggests that the etiology of SGA is usually associated with poor placental vascular development in early pregnancy. We examined metabolomic profiles using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) in three independent studies: (a) venous cord plasma from normal and SGA babies, (b) plasma from a rat model of placental insufficiency and controls, and (c) early pregnancy peripheral plasma s les from women who subsequently delivered a SGA baby and controls. Multivariate analysis by cross-validated Partial Least Squares Discriminant Analysis (PLS-DA) of all 3 studies showed a comprehensive and similar disruption of plasma metabolism. A multivariate predictive model combining 19 metabolites produced by a Genetic Algorithm-based search program gave an Odds Ratio for developing SGA of 44, with an area under the Receiver Operator Characteristic curve of 0.9. Sphingolipids, phospholipids, carnitines, and fatty acids were among this panel of metabolites. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of SGA offers insight into disease pathogenesis and offers the promise of a robust presymptomatic screening test.
Effect of oxygen on the expression of renin–angiotensin system components in a human trophoblast cell line
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.PLACENTA.2015.11.011
Abstract: During the first trimester, normal placental development occurs in a low oxygen environment that is known to stimulate angiogenesis via upregulation of vascular endothelial growth factor (VEGF). Expression of the placental renin-angiotensin system (RAS) is highest in early pregnancy. While the RAS and oxygen both stimulate angiogenesis, how they interact within the placenta is unknown. We postulated that low oxygen increases expression of the proangiogenic RAS pathway and that this is associated with increased VEGF in a first trimester human trophoblast cell line (HTR-8/SVneo). HTR-8/SVneo cells were cultured in one of three oxygen tensions (1%, 5% and 20%). RAS and VEGF mRNA expression were determined by qPCR. Prorenin, angiotensin converting enzyme (ACE) and VEGF protein levels in the supernatant, as well as prorenin and ACE in cell lysates, were measured using ELISAs. Low oxygen significantly increased the expression of both angiotensin II type 1 receptor (AGTR1) and VEGF (both P < 0.05). There was a positive correlation between AGTR1 and VEGF expression at low oxygen (r = 0.64, P < 0.005). Corresponding increases in VEGF protein were observed with low oxygen (P < 0.05). Despite no change in ACE1 mRNA expression, ACE levels in the supernatant increased with low oxygen (1% and 5%, P < 0.05). Expression of other RAS components did not change. Low oxygen increased AGTR1 and VEGF expression, as well as ACE and VEGF protein levels, suggesting that the proangiogenic RAS pathway is activated. This highlights a potential role for the placental RAS in mediating the proangiogenic effects of low oxygen in placental development.
Cardiovascular risk factors in women with previous gestational diabetes mellitus: A systematic review and meta-analysis
Publisher: Springer Science and Business Media LLC
Date: 27-10-2021
Early Pregnancy Prediction of Preeclampsia in Nulliparous Women, Combining Clinical Risk and Biomarkers
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2014
DOI: 10.1161/HYPERTENSIONAHA.114.03578
Abstract: More than half of all cases of preecl sia occur in healthy first-time pregnant women. Our aim was to develop a method to predict those at risk by combining clinical factors and measurements of biomarkers in women recruited to the Screening for Pregnancy Endpoints (SCOPE) study of low-risk nulliparous women. Forty-seven biomarkers identified on the basis of (1) association with preecl sia, (2) a biological role in placentation, or (3) a role in cellular mechanisms involved in the pathogenesis of preecl sia were measured in plasma s led at 14 to 16 weeks’ gestation from 5623 women. The cohort was randomly ided into training (n=3747) and validation (n=1876) cohorts. Preecl sia developed in 278 (4.9%) women, of whom 28 (0.5%) developed early-onset preecl sia. The final model for the prediction of preecl sia included placental growth factor, mean arterial pressure, and body mass index at 14 to 16 weeks’ gestation, the consumption of ≥3 pieces of fruit per day, and mean uterine artery resistance index. The area under the receiver operator curve (95% confidence interval) for this model in training and validation cohorts was 0.73 (0.70–0.77) and 0.68 (0.63–0.74), respectively. A predictive model of early-onset preecl sia included angiogenin lacental growth factor as a ratio, mean arterial pressure, any pregnancy loss weeks, and mean uterine artery resistance index (area under the receiver operator curve [95% confidence interval] in training and validation cohorts, 0.89 [0.78–1.0] and 0.78 [0.58–0.99], respectively). Neither model included pregnancy-associated plasma protein A, previously reported to predict preecl sia in populations of mixed parity and risk. In nulliparous women, combining multiple biomarkers and clinical data provided modest prediction of preecl sia.
Women's awareness of cardiovascular disease risk after complications of pregnancy
Publisher: Elsevier BV
Date: 05-2023
A Protocol for Nurse-Practitioner Led Cardiovascular Follow-Up After Pregnancy Complications in a Socioeconomically Disadvantaged Population
Publisher: Frontiers Media SA
Date: 08-01-2020
Effects of race and ethnicity on perinatal outcomes in high-income and upper-middle-income countries: an individual participant data meta-analysis of 2 198 655 pregnancies
Publisher: Elsevier BV
Date: 12-2022
Complex Interactions Between Hypoxia Inducible Factors, Insulin-Like Growth Factor-II and Oxygen in Early Murine Trophoblasts
Publisher: Elsevier BV
Date: 11-2007
DOI: 10.1016/J.PLACENTA.2007.05.009
Abstract: The human first trimester placenta experiences a low oxygen environment. The hypoxia inducible factors (HIFs) mediate the response to low oxygen, inducing genes such as insulin-like growth factor (IGF)-II. Interestingly, IGF-II has been shown to promote placental growth and function. Currently, the interaction between oxygen, IGF-II and HIFs in the regulation of trophoblast behaviour are unclear. Murine implantation sites from days 5.5-10.5 were collected for immunohistochemical analyses. Use of the hypoxia marker pimonidazole indicated that the early mouse implantation site is exposed to low oxygen levels similar to those seen in the early human placenta. HIF-1alpha protein immunostaining was also observed in the implantation site. Culturing murine ectoplacental cones in decreasing oxygen concentrations (20%, 5% and 1% O(2)), either with or without the addition of IGF-II, induced complex responses by trophoblasts in terms of their migration and differentiation. Following 3 days exposure to low oxygen there was reduced EPC outgrowth, reduced Igf2 and increased Tpbp mRNA levels, suggesting commitment to the spongiotrophoblast lineage. In addition, Hif-1alpha mRNA levels were decreased, whilst Hif-2alpha mRNA was unchanged. This decrease in Hif-1alpha may be due to the observed increase in antisense (as) Hif-1alpha mRNA levels in 1% cultures. Furthermore, expression of Hif-2alpha and the HIF target genes: asHif-1alpha, Vegf and Slc2a1 were reduced under low oxygen with the addition of IGF-II. In conclusion, Hif-1alpha and Hif-2alpha are differentially regulated by oxygen and IGF-II in cultured trophoblast cells and asHif-1alpha may mediate the response to prolonged hypoxia in murine trophoblasts.
Clinical Prediction in Early Pregnancy of Infants Small for Gestational Age by Customised Birthweight Centiles: Findings from a Healthy Nulliparous Cohort
Publisher: Public Library of Science (PLoS)
Date: 05-08-2013
Integrated Proteomics Pipeline Yields Novel Biomarkers for Predicting Preeclampsia
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2013
DOI: 10.1161/HYPERTENSIONAHA.113.01168
Abstract: Preecl sia, a hypertensive pregnancy complication, is largely unpredictable in healthy nulliparous pregnant women. Accurate preecl sia prediction in this population would transform antenatal care. To identify novel protein markers relevant to the prediction of preecl sia, a 3-step mass spectrometric work flow was applied. On selection of candidate biomarkers, mostly from an unbiased discovery experiment (19 women), targeted quantitation was used to verify and validate candidate biomarkers in 2 independent cohorts from the SCOPE (SCreening fOr Pregnancy Endpoints) study. Candidate proteins were measured in plasma specimens collected at 19 to 21 weeks’ gestation from 100 women who later developed preecl sia and 200 women without preecl sia recruited from Australia and New Zealand. Protein levels (n=25), age, and blood pressure were then analyzed using logistic regression to identify multimarker models (maximum 6 markers) that met predefined criteria: sensitivity ≥50% at 20% positive predictive value. These 44 algorithms were then tested in an independent European cohort (n=300) yielding 8 validated models. These 8 models detected 50% to 56% of preecl sia cases in the training and validation sets the detection rate for preterm preecl sia cases was 80%. Validated models combine insulin-like growth factor acid labile subunit and soluble endoglin, supplemented with maximally 4 markers of placental growth factor, serine peptidase inhibitor Kunitz type 1, melanoma cell adhesion molecule, selenoprotein P, and blood pressure. Predictive performances were maintained when exchanging mass spectrometry measurements with ELISA measurements for insulin-like growth factor acid labile subunit. In conclusion, we demonstrated that biomarker combinations centered on insulin-like growth factor acid labile subunit have the potential to predict preecl sia in healthy nulliparous women.
Elevated Maternal Folate Status and Changes in Maternal Prolactin, Placental Lactogen and Placental Growth Hormone Following Folic Acid Food Fortification: Evidence from Two Prospective Pregnancy Cohorts
Publisher: MDPI AG
Date: 23-03-2023
DOI: 10.3390/NU15071553
Abstract: Folic acid (FA) food fortification in Australia has resulted in a higher-than-expected intake of FA during pregnancy. High FA intake is associated with increased insulin resistance and gestational diabetes. We aimed to establish whether maternal one-carbon metabolism and hormones that regulate glucose homeostasis change in healthy pregnancies post-FA food fortification. Circulating folate, B12, homocysteine, prolactin (PRL), human placental lactogen (hPL) and placental growth hormone (GH2) were measured in early pregnancy maternal blood in women with uncomplicated pregnancies prior to (SCOPE: N = 604) and post (STOP: N = 711)-FA food fortification. FA food fortification resulted in 63% higher maternal folate. STOP women had lower hPL (33%) and GH2 (43%) after 10 weeks of gestation, but they had higher PRL (29%) and hPL (28%) after 16 weeks. FA supplementation during pregnancy increased maternal folate and reduced homocysteine but only in the SCOPE group, and it was associated with 54% higher PRL in SCOPE but 28% lower PRL in STOP. FA food fortification increased maternal folate status, but supplements no longer had an effect, thereby calling into question their utility. An altered secretion of hormones that regulate glucose homeostasis in pregnancy could place women post-fortification at an increased risk of insulin resistance and gestational diabetes, particularly for older women and those with obesity.
The Effect of Interactions between Folic Acid Supplementation and One Carbon Metabolism Gene Variants on Small-for-Gestational-Age Births in the Screening for Pregnancy Endpoints (SCOPE) Cohort Study
Publisher: MDPI AG
Date: 04-06-2020
DOI: 10.3390/NU12061677
Abstract: Small-for-gestational-age (SGA) is associated with significant perinatal morbidity and mortality. Our aim was to investigate gene-nutrient interactions between maternal one-carbon single nucleotide polymorphisms (SNPs) and folic acid supplement (FAS) use, and their association with SGA. Nulliparous New Zealand women with singleton pregnancy were recruited as part of the Screening for Pregnancy Endpoints prospective cohort study. Data on FAS use was collected via face-to-face interview at 15 weeks’ gestation participants were followed prospectively and birth outcome data collected within 72 h of delivery. Participants were genotyped for MTHFR 677, MTHFR 1298, MTHFD1 1958, MTR 2756, MTRR 66 and TCN2 776 SNPs. Genotype data for at least one SNP was available for 1873 (93%) of eligible participants. Analysis showed a significant SNP-FAS interaction for MTHFR 1298 (p = 0.020), MTHFR 677 (p = 0.019) and TCN2 776 (p = 0.017) in relation to SGA: MTHFR 1298 CC variant non-FAS users had an increased likelihood [Odds Ratio (OR) = 2.91 (95% Confidence Interval (CI) = 1.52, 5.60] compared with wild-type (MTHFR 1298 AA) FAS users. MTHFR 677 variant allele carrier (MTHFR 677 CT + MTHFR 677 TT) non-FAS users had an increased likelihood [OR = 1.87 (95% CI = 1.21, 2.88)] compared to wild-type (MTHFR 677 CC) FAS users. TCN2 776 variant (TCN2 776 GG) non-FAS users had an increased likelihood [OR = 2.16 (95% CI = 1.26, 3.71)] compared with wild type homozygote + heterozygote (TCN2 776 CC + TCN2 776 CG) FAS users. No significant interactions were observed for MTHFD1 1958, MTR 2756 or MTRR 66 (p 0.05). We observed an overall pattern of FAS attenuating differences in the likelihood of SGA seen between genotype groups in FAS non-users. Future research should focus on how intake of other one-carbon nutrients might mediate these gene-nutrient interactions.
Increased methylation and decreased expression of homeobox genes TLX1, HOXA10 and DLX5 in human placenta are associated with trophoblast differentiation
Publisher: Springer Science and Business Media LLC
Date: 03-07-2017
DOI: 10.1038/S41598-017-04776-5
Abstract: Homeobox genes regulate embryonic and placental development, and are widely expressed in the human placenta, but their regulatory control by DNA methylation is unclear. DNA methylation analysis was performed on human placentae from first, second and third trimesters to determine methylation patterns of homeobox gene promoters across gestation. Most homeobox genes were hypo-methylated throughout gestation, suggesting that DNA methylation is not the primary mechanism involved in regulating HOX genes expression in the placenta. Nevertheless, several genes showed variable methylation patterns across gestation, with a general trend towards an increase in methylation over gestation. Three genes ( TLX1, HOXA10 and DLX5 ) showed inverse gains of methylation with decreasing mRNA expression throughout pregnancy, supporting a role for DNA methylation in their regulation. Proteins encoded by these genes were primarily localised to the syncytiotrophoblast layer, and showed decreased expression later in gestation. siRNA mediated downregulation of DLX5 , TLX1 and HOXA10 in primary term villous cytotrophoblast resulted in decreased proliferation and increased expression of differentiation markers, including ERVW-1 . Our data suggest that loss of DLX5, TLX1 and HOXA10 expression in late gestation is required for proper placental differentiation and function.
Author response to: Cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: systematic review and meta-analysis
Publisher: Cambridge University Press (CUP)
Date: 04-04-2022
DOI: 10.1017/S2040174422000174
Abstract: This commentary is an author response to Yu and colleagues regarding the manuscript entitled ‘ Cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: Systematic review and meta-analysis’. We address their concern regarding minor errors in our manuscript, our search strategy and assessment of heterogeneity.
Is the US failing women?
Publisher: Elsevier BV
Date: 2021
Author response to: Cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: systematic review and meta-analysis – ERRATUM
Publisher: Cambridge University Press (CUP)
Date: 21-06-2022
Remodelling of the bovine placenta: Comprehensive morphological and histomorphological characterization at the late embryonic and early accelerated fetal growth stages
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.PLACENTA.2017.04.009
Abstract: Placental function impacts growth and development with lifelong consequences for performance and health. We provide novel insights into placental development in bovine, an important agricultural species and biomedical model. Concepti with defined genetics and sex were recovered from nulliparous dams managed under standardized conditions to study placental gross morphological and histomorphological parameters at the late embryo (Day48) and early accelerated fetal growth (Day153) stages. Placentome number increased 3-fold between Day48 and Day153. Placental barrier thickness was thinner, and volume of placental components, and surface areas and densities were higher at Day153 than Day48. We confirmed two placentome types, flat and convex. At Day48, there were more convex than flat placentomes, and convex placentomes had a lower proportion of maternal connective tissue (P < 0.01). However, this was reversed at Day153, where convex placentomes were lower in number and had greater volume of placental components (P < 0.01- P < 0.001) and greater surface area (P < 0.001) than flat placentomes. Importantly, embryo (r = 0.50) and fetal (r = 0.30) weight correlated with total number of convex but not flat placentomes. Extensive remodelling of the placenta increases capacity for nutrient exchange to support rapidly increasing embryo-fetal weight from Day48 to Day153. The cellular composition of convex placentomes, and exclusive relationships between convex placentome number and embryo-fetal weight, provide strong evidence for these placentomes as drivers of prenatal growth. The difference in proportion of maternal connective tissue between placentome types at Day48 suggests that this tissue plays a role in determining placentome shape, further highlighting the importance of early placental development.
Relative importance of metabolic syndrome components for developing gestational diabetes
Publisher: Springer Science and Business Media LLC
Date: 16-10-2022
DOI: 10.1007/S00404-021-06279-1
Abstract: To assess the independent and joint contribution of the in idual components of metabolic syndrome, and known risk factors for gestational diabetes (GDM), on risk of GDM. Two thousand nine hundred and fifteen women from Australia and New Zealand, who participated in The Screening for Pregnancy Endpoints Study (SCOPE), were included. Using the SCOPE clinical data set and biomarkers obtained at 14-16 weeks' gestation, a logistic regression model was fitted to the binary outcome GDM, with in idual metabolic syndrome components (waist circumference, blood pressure, glucose, HDL-C, triglycerides), recruitment site, and other established factors associated with GDM. Hierarchical partitioning was used to assess the relative contribution of each variable. Of the 2915 women, 103 women (3.5%) developed GDM. The deviance explained by the logistic regression model containing all variables was 18.65% and the AUC was 0.809. Seventy percent of the independent effect was accounted for by metabolic syndrome components. The highest independent relative contribution to GDM was circulating triglycerides (17 ± 3%), followed by waist circumference (13 ± 3%). Glucose and maternal BMI contributed 12 ± 2% and 12 ± 3%, respectively. The remaining factors had an independent relative contribution of < 10%. Triglyceride concentrations had the highest independent relative importance for risk of GDM. Increased focus for lowering triglycerides as an important risk factor for GDM is warranted.
Use of Matrigel in culture affects cell phenotype and gene expression in the first trimester trophoblast cell line HTR8/SVneo
Publisher: Elsevier BV
Date: 07-2012
DOI: 10.1016/J.PLACENTA.2012.04.003
Abstract: There is inconsistent use of Matrigel for experiments with the HTR8/SVneo first trimester trophoblast and other cell lines. We quantified the effects of Matrigel on the expression of genes considered to be markers of extravillous cytotrophoblast (EVT) differentiation and invasive potential. Culture on Matrigel promoted formation of "endothelial-like" tubes and reduced mRNA expression of matrix metalloproteinase 2 (MMP2), cytokeratin 7 (KRT7) and integrin alpha 1 (ITGA1), while increasing VE-cadherin (CDH5) expression consistent with a vascular phenotype. This process may constitute part of the endothelial cell mimicry exhibited by endovascular EVTs invading the maternal spiral arteries. HTR8/SVneo appears to be phenotypically polymorphic and adopt endovascular morphology on Matrigel.
Risk Factors for Preterm Birth in an International Prospective Cohort of Nulliparous Women
Publisher: Public Library of Science (PLoS)
Date: 16-07-2012
Vascular endothelial growth factor family gene polymorphisms in preeclampsia in Sinhalese women in Sri-Lanka
Publisher: Informa UK Limited
Date: 21-11-2012
DOI: 10.3109/14767058.2012.743520
Abstract: To investigate the association of polymorphisms in the vascular endothelial growth factor (VEGF) family genes (VEGFA rs699947, VEGFA rs3025039, PGF rs1042886, KDR rs2071559 and KDR rs2305948) with preecl sia in Sinhalese women in Sri-Lanka. We conducted a case-control study where 175 nulliparous Sinhalese women with preecl sia and 171 normotensive women matched for age, ethnicity, parity and BMI were recruited in tertiary care maternity hospitals in Sri-Lanka. Preecl sia was diagnosed using international guidelines. DNA extracted from peripheral venous blood and was genotyped using the Sequenom MassARRAY system. χ(2)-test was used to compare the distribution of allele and genotype frequencies between the cases and the control subjects. The frequency of PGF rs1042886 variant allele (odds ratio (OR) 1.5, 95% confidence interval (CI) 1.1-2.1) and dominant genotype model (aOR 1.6, 95% CI 1.0-2.4) were increased in preecl tic women compared to controls. VEGFA rs699947, VEGFA rs3025039, KDR rs2071559, and KDR rs2305948 polymorphisms were not associated with preecl sia. Maternal PGF rs1042886 polymorphism is associated with preecl sia in Sinhalese women in Sri-Lanka.
Antiserum to the egg coats of the fat-tailed dunnart (Marsupialia, Dasyuridae) cross-reacts with egg coats of other marsupial and eutherian species
Publisher: Wiley
Date: 15-06-1997
DOI: 10.1002/(SICI)1097-010X(19970615)278:3<133::AID-JEZ2>3.0.CO;2-P
Abstract: We are examining the extracellular coats of the brush-tailed possum as a possible target for an immunocontraceptive vaccine for biocontrol of this pest species in New Zealand. In this study we have compared the composition of the extracellular coats of the fat-tailed and stripe-faced dunnarts, brush-tailed possum, domestic rabbit, and laboratory mouse using histochemistry, immunocytochemistry, and immunofluorescence. The histochemistry of the luminal epithelium of the oviduct and mucoid coats of the marsupials and rabbit indicated that they contain acidic glycoproteins. Immunofluorescence showed that polyclonal antiserum raised against the extracellular coats of the oocyte and early embryo of the fat-tailed dunnart, cross-reacted with the extracellular coats of the oocytes of all five species. These results suggest that there are common epitopes on the extracellular coats of oocytes and early embryos of distinctly related therian species. Further work to characterise these proteins is required to determine whether there is close homology between the oviductal glycoproteins of these species.
Autonomic control of the pulmonary surfactant system and lung compliance inl the lizard
Publisher: University of Chicago Press
Date: 07-1997
DOI: 10.1086/515847
Abstract: An increase in body temperature in the bearded dragon, Pogona vitticeps, is accompanied by an increase in the amount of pulmonary surfactant, a mixture of proteins and lipids, with the latter consisting predominantly of phospholipid and cholesterol. This increase may result from a temperature-induced change in autonomic input to the lungs, as perfusing the isolated lungs of P. vitticeps with either acetylcholine or adrenaline increases surfactant phospholipid release. However, whether acetylcholine acts via intrapulmonary sympathetic ganglia or directly on alveolar Type II cells is unknown. Moreover, the relative importance of circulating catecholamines and pulmonary sympathetic nerves on the control of the surfactant system is also obscure. Here, we describe the mechanism of the modulation of the surfactant system and the effect of this modulation on lung compliance. The role of acetylcholine was determined by perfusing isolated lungs with acetylcholine, acetylcholine and the ganglionic antagonist hexamethonium, or acetylcholine, hexamethonium, and the muscarinic antagonist atropine. Perfusing with acetylcholine significantly increased phospholipid release but did not affect cholesterol release. While histological examination of the lung revealed the presence of a large autonomic ganglion at the apex, blocking sympathetic ganglia with hexamethonium did not prevent the acetylcholine-mediated increase in phospholipid. However, the increase was inhibited by blocking muscarinic receptors with atropine, which indicates that acetylcholine acts on muscarinic receptors to stimulate phospholipid release. By increasing pulmonary smooth muscle tone, acetylcholine decreased opening pressure and increased static inflation pressures. Plasma levels of noradrenaline and adrenaline increased with increasing temperature and were accompanied by a greater surfactant content in the lungs. While surfactant content was also higher in animals that exercised, plasma levels of adrenaline, noradrenaline, and dopamine were not elevated following exercise. Hence, surfactant release in the lizard lung may increase in response to an increase in plasma catecholamine levels. Acetylcholine, and hence the parasympathetic nervous system, may act to stimulate surfactant release but does not act via pulmonary sympathetic ganglia. We conclude that promoting surfactant secretion via an increase in circulating catecholamines may be inappropriate for a cold lizard with a requirement to conserve energy. As body temperature decreases, release of surfactant via nonadrenergic mechanisms, including cholinergic stimulation, may become increasingly important.
Pregnancy Complications Are Associated with Premature Coronary Artery Disease
Publisher: Mary Ann Liebert Inc
Date: 10-10-2023
Early pregnancy cardio metabolic risk factors and the prevalence of metabolic syndrome 10 years after the first pregnancy
Publisher: Public Library of Science (PLoS)
Date: 20-01-2023
DOI: 10.1371/JOURNAL.PONE.0280451
Abstract: We aimed to compare risk factors for CVD 10 years postpartum among women who had ≥ 1 compared to no cardio metabolic risk factor in early first pregnancy. Women of the SCOPE (Screening fOr Pregnancy Endpoints) study from Adelaide, South Australia were invited to participate in a cardiovascular risk assessment 10 years after the delivery of the first child. Data from 141 women who completed all the assessments are included in the analyses. Compared to women who did not have any cardio metabolic risk factor at 15 ± 1 weeks’ gestation during the first pregnancy, those who had ≥ 1 risk factor were 5.5 times more likely to have metabolic syndrome 10 years postpartum (aOR = 5.5, 95% CI 1.8–17.3, p = 0.004). Women who had ≥ 1cardio metabolic risk factor during the first pregnancy were more likely to be obese (p = 0.001), have high total cholesterol levels (p .001) or have increased insulin resistance (p .001) 10 years later compared to women who had no risk factor during the first pregnancy. 63.5% of the women with no cardio metabolic risk factor compared to 39% of women who had ≥ 1 risk factor in first pregnancy, had neither a complicated first pregnancy nor was diagnosed with MetS 10 years postpartum (p = 0.023). Cardio metabolic risk factors at the booking visit in the first pregnancy may be useful in identifying young women at risk of future CVD.
Protective Influence of Breastfeeding on Cardiovascular Risk Factors in Women With Previous Gestational Diabetes Mellitus and Their Children: A Systematic Review and Meta-Analysis
Publisher: SAGE Publications
Date: 05-10-2022
DOI: 10.1177/08903344211034779
Abstract: There is evidence that breastfeeding may provide protection against cardiovascular risk factors in mothers with a history of gestational diabetes mellitus and their children who were exposed in utero. To perform a systematic review and meta-analysis of observational studies to ascertain the effects of breastfeeding on cardiovascular risk factors in women with previous gestational diabetes mellitus and their children exposed in utero. Studies assessing conventional cardiovascular risk factors in women with previous gestational diabetes mellitus and children exposed in utero stratified by breastfeeding/no breastfeeding or breastfed/not breastfed were included. Gestational diabetes mellitus was defined based on the International Association of Diabetes in Pregnancy Study Group definition or previous accepted definitions. Breastfeeding was defined as reported in each study. The literature search yielded 260 titles, of which 17 studies were selected to be in the review. Women with previous gestational diabetes mellitus who did not breastfeed had higher blood glucose ( SMD: 0.32, 95% CI [0.12, 0.53]) and a greater risk of developing Type 2 diabetes mellitus ( RR: 2.08 95% CI [1.44, 3.00]) compared to women with no history. There were not enough studies to conduct a meta-analysis on the effects of breastfeeding on risk factors for cardiovascular disease among children exposed to gestational diabetes mellitus in utero. Breastfeeding appears to be protective against cardiovascular risk factors among women who experience gestational diabetes mellitus.
Effect of Birth Weight and Early Pregnancy BMI on Risk for Pregnancy Complications
Publisher: Wiley
Date: 19-12-2018
DOI: 10.1002/OBY.22375
Abstract: This study investigated the influence of birth weight on the risk of pregnancy complications, including preecl sia (PE), gestational hypertension (GH), small for gestational age (SGA) pregnancy, spontaneous preterm birth, and gestational diabetes mellitus (GDM), and assessed the effect of early pregnancy BMI on this relationship. A total of 5,336 nulliparous women from the SCreening fOr Pregnancy Endpoints (SCOPE) study were included. Women's birth weights were self-reported and confirmed via medical records when possible. A birth weight of 3,000 to 3,499 g was considered the reference. After adjusting for confounders, birth weight < 2,500 g was associated with increased risk of GH (adjusted odds ratio [aOR] = 2.2, 95% CI = 1.3-3.7), PE (aOR = 1.7, 95% CI = 1.0-2.9), small for gestational age (aOR = 1.9, 95% CI = 1.1-3.2), and GDM (aOR = 2.4, 95% CI = 1.0-5.8) compared with the referent. Women born with birth weight < 2,500 g and who subsequently developed overweight or were diagnosed with obesity were at increased risk of GH (aOR = 2.2, 95% CI = 1.1-4.5), PE (aOR = 2.3, 95% CI = 1.2-4.5), and GDM (aOR = 3.2, 95% CI = 1.1-9.5) compared with women with birth weight ≥ 2,500 g and remained lean. Women who were born with a low birth weight are at increased risk of pregnancy complications. Those born small may have undergone "programming" in response to unfavorable intrauterine conditions. In such women, the physiological demands of pregnancy may act as a "second hit," leading to pregnancy complications.
The Insulin-like Growth Factor System in Mammalian Pregnancy—A Workshop Report
Publisher: Elsevier BV
Date: 04-2004
Embryo number and periconceptional undernutrition in the sheep have differential effects on adrenal epigenotype, growth, and development
Publisher: American Physiological Society
Date: 15-07-2014
DOI: 10.1152/AJPENDO.00051.2012
Abstract: Exposure to poor maternal nutrition around the time of conception results in an early prepartum activation of the fetal pituitary-adrenal axis and in increased adrenal growth and stress response after birth associated with epigenetic changes in a differentially methylated region (DMR) of adrenal IGF2/H19. We have determined the effects of maternal undernutrition during the periconceptional period (PCUN: 70% of control intake from 60 days before until 6 days after conception) and early preimplantation period (PIUN: 70% of control intake for 6 days after conception) on fetal plasma ACTH and cortisol concentrations and fetal adrenal ACTHR, StAR, 3βHSD, CYP11B, CYP17, TGFβ1, IGF1, IGF1R, IGF2, and IGF2R mRNA expression and the methylation level of sites within the DMRs of IGF2/H19 and IGF2R in the adrenal of twin and singleton fetuses at 136–138 days gestation. Being a twin resulted in a delayed prepartum increase in fetal ACTH and in a lower cortisol response to CRH in the control but not PCUN and PIUN groups. PCUN, but not PIUN, resulted in an increase in adrenal weight and CYP17 expression in singletons, a decrease in adrenal IGF2 expression in singletons, and an increase in adrenal IGF2R expression in both twins and singletons. IGF2/H19 and IGF2R DMR methylation levels and ACTHR expression were lower in the twin adrenal. Thus, exposure of the oocyte and embryo to maternal undernutrition or to the environment of a twin pregnancy have differential effects on epigenetic and other factors that regulate fetal adrenal growth and IGF2 and IGF2R expression.
Young-Onset Gastrointestinal Adenocarcinoma Incidence and Survival Trends in the Northern Territory, Australia, with Emphasis on Indigenous Peoples
Publisher: MDPI AG
Date: 10-06-2022
Abstract: Background and Aims: A concerning rise in incidence of young-onset cancers globally led to the examination of trends in incidence and survival of gastrointestinal (GI) adenocarcinomas in the Northern Territory (NT), Australia, over a 28-year period, with a special emphasis on Indigenous peoples. Methods: This cross-sectional analysis of a prospective longitudinal database, NT Cancer Registry (1990–2017), includes all reported cases of GI (oesophagus, gastric, small intestinal, pancreas, colon, and rectum) adenocarcinomas. Poisson regression was used to estimate incidence ratio ratios, and survival was modelled using Cox proportional hazard models separately for people aged 18–50 years and years. Results: A total of 1608 cases of GI adenocarcinoma were recorded during the time of the study. While the overall incidence in people 18–50 years remained unchanged over this time (p = 0.51), the rate in in iduals aged years decreased (IRR = 0.65 (95% CI 0.56–0.75 p 0.0001)). Incidence rates were significantly less in females years (IRR = 0.67 95% CI 0.59–0.75 p 0.0001), and their survival was significantly better (HR = 0.84 (95%CI 0.72–0.98 p 0.03)) compared to males. Overall survival across all GI subsites improved in both age cohorts, especially between 2010 and 2017 (HR = 0.45 (95%CI 0.29–0.72 p 0.0007) and HR = 0.64 (95%CI 0.52–0.78 p 0.0001), respectively) compared to 1990–1999, driven by an improvement in survival in colonic adenocarcinoma alone, as the survival remained unchanged in other GI subsites. The incidence was significantly lower in Indigenous patients compared to non-Indigenous patients, in both age cohorts (18–50 years IRR = 0.68 95% CI 0.51–0.91 p 0.009 and years IRR = 0.48 95% CI 0.40–0.57 p 0.0001). However, Indigenous patients had worse survival rates (18–50 years HR = 2.06 95% CI 1.36–3.11 p 0.0007 and years HR = 1.66 95% CI 1.32–2.08 p 0.0001). Conclusions: There is a trend towards an increased incidence of young-onset GI adenocarcinomas in the NT. Young Indigenous patients have lower incidence but worse survival across all GI subsites, highlighting significant health inequities in life expectancy. Targeted, culturally safe Indigenous community-focussed programs are needed for early detection and patient-centred management of GI adenocarcinomas.
Growth and function of the normal human placenta
Publisher: Elsevier BV
Date: 2004
DOI: 10.1016/J.THROMRES.2004.06.038
Abstract: The placenta is the highly specialised organ of pregnancy that supports the normal growth and development of the fetus. Growth and function of the placenta are precisely regulated and coordinated to ensure the exchange of nutrients and waste products between the maternal and fetal circulatory systems operates at maximal efficiency. The main functional units of the placenta are the chorionic villi within which fetal blood is separated by only three or four cell layers (placental membrane) from maternal blood in the surrounding intervillous space. After implantation, trophoblast cells proliferate and differentiate along two pathways described as villous and extravillous. Non-migratory, villous cytotrophoblast cells fuse to form the multinucleated syncytiotrophoblast, which forms the outer epithelial layer of the chorionic villi. It is at the terminal branches of the chorionic villi that the majority of fetal/maternal exchange occurs. Extravillous trophoblast cells migrate into the decidua and remodel uterine arteries. This facilitates blood flow to the placenta via dilated, compliant vessels, unresponsive to maternal vasomotor control. The placenta acts to provide oxygen and nutrients to the fetus, whilst removing carbon dioxide and other waste products. It metabolises a number of substances and can release metabolic products into maternal and/or fetal circulations. The placenta can help to protect the fetus against certain xenobiotic molecules, infections and maternal diseases. In addition, it releases hormones into both the maternal and fetal circulations to affect pregnancy, metabolism, fetal growth, parturition and other functions. Many placental functional changes occur that accommodate the increasing metabolic demands of the developing fetus throughout gestation.
Mechanistic Insight into Long Noncoding RNAs and the Placenta
Publisher: MDPI AG
Date: 27-06-2017
DOI: 10.3390/IJMS18071371
Origin of the oocyte shell membrane of a dasyurid marsupial: An immunohistochemical study
Publisher: Wiley
Date: 11-1994
Abstract: Polyclonal antibodies were raised against the extracellular coats (mucoid and shell membrane) of unfertilized oocytes and early embryos of a dasyurid marsupial, the fat-tailed dunnart (Sminthopsis crassicaudata). Indirect immunofluorescence was used to test the specificity of the antibodies to the shell membrane. Streptavidin/biotin immunoperoxidase cytochemistry revealed that precursors of the tertiary egg membranes are secreted by the luminal epithelium of the ulla, isthmus (including the crypts), utero-tubal junction, and adjacent endometrial glands. Histochemistry distinguished between the sites of mucoid and shell membrane precursor secretion. The mucoid coat stained positively with Alcian blue at pH 1.0 and 2.5, with Alcian blue at pH 0.2 after performic acid oxidation, and with PAS which was amylase resistant. Some of the luminal epithelial cells of the ulla and isthmus, as well as its crypts, also stained positively by these histochemical methods but the luminal epithelium of the utero-tubal junction and endometrial glands were negative for all methods. The shell membrane did not stain with any of the above methods nor with dihydroxy-dinapthyl-disulphide (DDD) or ferric ferricyanide but it was eosinophilic and stained positively with the red cytoplasmic stain of Masson's trichrome. Therefore, it is concluded that shell membrane precursors are secreted by the luminal epithelium of the utero-tubal junction, adjacent glands, and by scattered glands in the anterior region of the uterus but not by any cell population of the oviduct.
Placental transcriptome co-expression analysis reveals conserved regulatory programs across gestation.
Publisher: Springer Science and Business Media LLC
Date: 03-01-2017
IFPA Meeting 2012 Workshop Report II: Epigenetics and imprinting in the placenta, growth factors and villous trophoblast differentiation, role of the placenta in regulating fetal exposure to xenobioti
Publisher: Elsevier BV
Date: 03-2013
The effect of Vdr gene ablation on global gene expression in the mouse placenta
Publisher: Elsevier BV
Date: 12-2015
Cultural adaptation of an Aboriginal and Torres Strait Islanders maternal and child mobile health intervention: Protocol for a co-design and adaptation research study. (Preprint)
Publisher: JMIR Publications Inc.
Date: 23-10-2023
Author response: cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: systematic review and meta-analysis
Publisher: Cambridge University Press (CUP)
Date: 13-04-2020
DOI: 10.1017/S2040174420000185
Abstract: This commentary is an author response to Lu and Wang, regarding the manuscript entitled ‘Cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: Systematic review and meta-analysis’. We address their concern regarding duplication of studies in the meta-analysis and the quality of included studies.
Effect of culturing mouse embryos under different oxygen concentrations on subsequent fetal and placental development.
Publisher: Wiley
Date: 28-03-2006
Vitamin D levels in an Australian and New Zealand cohort and the association with pregnancy outcome
Publisher: Springer Science and Business Media LLC
Date: 20-06-2018
Urinary angiotensinogen excretion in Australian Indigenous and non-Indigenous pregnant women
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.
IFPA Award in Placentology Lecture: Complicated interactions between genes and the environment in placentation, pregnancy outcome and long term health
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.PLACENTA.2010.01.001
Abstract: Most research on the developmental origins of health and disease has implicated poor nutrition in the fetus, most often conferred by deficiencies in maternal nutrition, as an important causal factor that programmes offspring physiology for adult disease. Emerging evidence implicates interactions between genes and the environment that may help to explain why poor growth before birth is associated with a variety of adult onset diseases that appear in different in iduals of the same birthweight. However, it is underappreciated that the placenta, particularly trophoblast invasion, is key to health of both the mother and child in both the short and long term and that the role of the father is more important than perhaps ever expected. Intrauterine growth restriction (IUGR) is but one of a continuum of several pregnancy complications that may be related and that may reflect the long term health of both parents and offspring. These include preecl sia, pre-term birth and gestational diabetes, as well as IUGR. Polymorphisms in genes that regulate how the placenta invades maternal tissues, differentiates and functions and how the mother adapts to pregnancy have been identified as candidates that confer risk to pregnancy success. Potentially, pregnancy provides a window that gives clues to modifiable risk factors that should be addressed early to ameliorate late adult disease. Placentation and trophoblast invasion and its inhibitors in other species may provide new ideas for understanding what goes wrong in human pregnancy. Placentologists and clinicians may usefully collaborate to identify factors that predict risk for pregnancy complications and poor health later in life.
Seasonality of hypertensive disorders of pregnancy – A South Australian population study
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.PREGHY.2018.04.006
Abstract: To investigate the seasonal variation of hypertensive disorders of pregnancy (HDP) in South Australia. Retrospective population study including all 107,846 liveborn singletons during 2007-2014 in South Australia. Seasonality in incidence of HDP in relation to estimated date of conception (eDoC) and date of birth (DoB) were examined using Fourier series analysis. Seasonality of HDP in relation to eDoC and DoB. During 2007-2014, the incidence of HDP was 7.1% (n = 7,612). Seasonal modeling showed a strong relationship between HDP and eDoC (p < .001) and DoB (p < .001). Unadjusted and adjusted models (adjusted for maternal age, body mass index, ethnicity, parity, type of health care, smoking and gestational diabetes mellitus) demonstrated the presence of a peak incidence (7.8%, 7.9% respectively) occurring among pregnancies with eDoC in late Spring (November) and a trough (6.4% and 6.3% respectively) among pregnancies with eDoC in late Autumn (May). Both unadjusted and adjusted seasonal modelling showed a peak incidence of HDP for pregnancies with DoB in August (8.0%, 8.1% respectively) and a nadir among pregnancies with eDoB in February (6.2%). The highest incidence of HDP was associated with pregnancies with eDoC during late spring and summer and birth in winter, while the lowest incidence of HDP was associated with pregnancies with eDoC during late autumn and early winter and birth in summer. Nutrient intake, in particular vitamin D, sunlight exposure and physical activity may affect maternal, fetal and placental adaptation to pregnancy and are potential contributors to the seasonal variation of HDP.
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Discovery Projects - Grant ID: DP0453363
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End Date: 10-2007
Amount: $240,000.00
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View Funded ActivityResearch Networks - Grant ID: RN0457079
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End Date: 08-2009
Amount: $1,500,000.00
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