Offspring Sex Impacts DNA Methylation and Gene Expression in Placentae from Women with Diabetes during Pregnancy
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PROVIDER: PRJNA433053 | ENA |
REPOSITORIES: ENA
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Project description:Offspring Sex Impacts DNA Methylation and Gene Expression in Placentae from Women with Diabetes during Pregnancy
| PRJNA433054 | ENA
Project description:Maternal obesity in pregnancy is associated with increased birth-weight, obesity and premature mortality in adult offspring. The Effect of Metformin on Maternal and Fetal Outcomes in Pregnant Obese Women (EMPOWaR) trial was a randomised, double-blind, placebo-controlled trial carried out to determine whether exposure to Metformin would affect the offspring birth-weight centile. Obese women exposed to Metformin had increased insulin sensitivity at 36 weeks of pregnancy, but there were no differences in offspring birthweight. We obtained the placentas from these women to determine whether there were differences in expression of genes regulating fetal growth and metabolism. In a complementary study we investigated DNA methylation in the same samples.
2019-01-31 | E-MTAB-6418 | biostudies-arrayexpress
Project description:Maternal obesity in pregnancy is associated with increased birth-weight, obesity and premature mortality in adult offspring. The Effect of Metformin on Maternal and Fetal Outcomes in Pregnant Obese Women (EMPOWaR) trial was a randomised, double-blind, placebo-controlled trial carried out to determine whether exposure to Metformin would affect the offspring birth-weight centile. Obese women exposed to Metformin had increased insulin sensitivity at 36 weeks of pregnancy, but there were no differences in offspring birthweight. We obtained the placentas from these women to determine whether there were differences in DNA methylation of genes regulating fetal growth and metabolism. In a related study we investigated the gene expression in the same samples.
2018-11-01 | E-MTAB-6421 | biostudies-arrayexpress
Project description:AIMS/HYPOTHESIS: Pregnancies complicated by diabetes have a higher risk of adverse outcomes for mothers and children, including predisposition to disease later in life, such as metabolic syndrome and hypertension. We hypothesized that adverse outcomes from diabetic pregnancies may be linked to compromised placental function. Our goal in this study was to identify cellular and molecular abnormalities in diabetic placenta. METHODS: Using a mouse model of diabetic pregnancy, placental gene expression was assayed at midgestation and cellular composition was analyzed at various stages. Genome-wide expression profiling was validated by quantitative PCR, and tissue localization studies were performed to identify cellular correlates of altered gene expression in diabetic placenta. RESULTS: We detected significantly altered gene expression in diabetic placenta for genes expressed in the maternal as well as those in the embryonic compartments. We also found altered cellular composition of the decidual compartment. Furthermore, the junctional and labyrinth layers were reduced in diabetic placenta, accompanied by aberrant differentiation of spongiotrophoblast cells. CONCLUSIONS/INTERPRETATION: Diabetes during pregnancy alters transcriptional profiles in the murine placenta, affecting cells of both embryonic and maternal origin, and involving several genes not previously implicated in diabetic pregnancies. The molecular changes and abnormal differentiation of multiple cell types precede impaired growth of junctional zone and labyrinth, and placenta overall. Whether these changes represent direct responses to hyperglycaemia or physiological adaptations, they are likely to play a role in pregnancy complications and outcomes, and have implications for developmental origins of adult disease. The STZ diabetic mouse model was used to investigate gene expression changes in diabetic placentae at E10.5. Placentae were dissected from 5 different FVB dams at embryonic day 10.5 under diabetic conditions and from 5 control dams. Gene expression profiles from five individual placentae from independent pregnancies per group were compared.
2011-06-01 | E-GEOD-28277 | biostudies-arrayexpress
Project description:Aims/hypothesisWe hypothesized that diabetes during pregnancy (DDP) alters genome-wide DNA methylation in placenta resulting in differentially methylated loci of metabolically relevant genes and downstream changes in RNA and protein expression.MethodsWe mapped genome-wide DNA methylation with the Infinium 450K Human Methylation Bead Chip in term fetal placentae from Native American and Hispanic women with DDP using a nested case-control design (n = 17 pairs). RNA expression and protein levels were assayed via RNA-Seq and Western Blot.ResultsGenome-wide DNA methylation analysis revealed 465 CpG sites with significant changes for male offspring, 247 for female offspring, and 277 for offspring of both sexes (p<0.001). Placentae from female offspring were 40% more likely to have significant gains in DNA methylation compared with placentae from male offspring exposed to DDP (p<0.001). Changes in DNA methylation corresponded to changes in RNA and protein levels for 6 genes: PIWIL3, CYBA, GSTM1, GSTM5, KCNE1 and NXN. Differential DNA methylation was detected at loci related to mitochondrial function, DNA repair, inflammation, oxidative stress.Conclusions/interpretationThese findings begin to explain mechanisms responsible for the increased risk for obesity and type 2 diabetes in offspring of mothers with DDP.
| S-EPMC5823368 | biostudies-literature
Project description:Purpose: to determine whether exposure to chronic low dose dioxin impacts pancreas physiology during pregnancy (dams) and/or pancreas development (offspring)
2023-02-04 | GSE144793 | GEO
Project description:Gestational diabetes (GDM) is a distinctive form of diabetes that first presents in pregnancy. While most women return to normoglycemia after delivery, they are predisposed to an accelerated development of type 2 diabetes. Current prevention strategies remain limited due to our incomplete understanding of the early underpinnings of progression. We therefore examined the protein profiles of women shortly after a GDM pregnancy (using a nested case-control study design within the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy) for a comprehensive mechanistic inquiry. At 6-9 weeks postpartum (baseline), differences between women who later developed diabetes (case group) and those who did not (control group) were detected. Notably, protein profiles comprised protease inhibitors, extracellular matrix components, and lipoprotein molecules involved in inflammation. We also identified co-expression networks of differentially altered triglycerides and protein involved in wound healing, highlighting the interplay between dyslipidemia and inflammation. Overall, our findings warrant earlier intervention than previously thought, as defects in postpartum wound healing after a GDM pregnancy, in association with dysmetabolism and insulin resistance, may accelerate type 2 diabetes progression.
2024-09-04 | PXD041243 | Pride
Project description:Pregnancy loss is the most common complication of human pregnancy. Recurrent early pregnancy loss (REPL) has multiple etiologies, including endometrial dysregulation leading to “suboptimal” implantation. Although the implantation process is tightly regulated in Eutherian (placental) mammals, the molecular factors contributing to dysregulated endometrial gene expression patterns in women with REPL are largely unknown. We hypothesized that genes that gained novel expression in the endometria of mammals that evolved in the Eutherian stemlineage, coincident with the evolution of pregnancy, are likely essential for establishment and maintenance of normal pregnancy and are, therefore, good candidates for genes whose expression may be dysregulated in disorders such as REPL. To test this hypothesis, we took an evolutionary forward genomics approach to characterize gene expression profiles of midsecretory endometria from women with REPL associated with abnormal endometria based either on histology or molecular expression of cyclin E. We identified 58 genes that were differentially expressed (P<0.001) between women with out-of-phase histological dating vs normal histology, and 81 genes that were differentially expressed (P<0.001) between women with abnormally elevated cyclin E levels vs normal cyclin E. Remarkably, genes that were recruited into endometrial expression during the evolution of pregnancy in Eutherian mammals were significantly enriched for dysregulated genes (P=0.002 for histology, P=0.021 for cyclin E), as well as for immune and signaling pathways with essential roles in endometrial biology. Thus, our novel evolutionary-based forward genomics approach identified genes whose dysregulation during the mid-secretory phase likely contributes to the molecular etiologies of recurrent early pregnancy loss. Total RNA obtained from mid luteal phase endometrium (two replicates per biopsy) from women with recurrent early pregnancy loss (REPL). Endometrial gene expression levels were compared 1) between women with out-of-phase (n=10) and normal histological dating (n=22), 2) between women with abnormally elevated (n=9) and normal (n=23) cyclin E levels. For 5 additional women with abnormally high cyclin E levels, biopsy samples were collected before and after progesterone treatment to investigate the gene expression profiles in response to progesterone.
2014-12-06 | E-GEOD-63901 | biostudies-arrayexpress
Project description:Pregnancy loss is the most common complication of human pregnancy. Recurrent early pregnancy loss (REPL) has multiple etiologies, including endometrial dysregulation leading to “suboptimal” implantation. Although the implantation process is tightly regulated in Eutherian (placental) mammals, the molecular factors contributing to dysregulated endometrial gene expression patterns in women with REPL are largely unknown. We hypothesized that genes that gained novel expression in the endometria of mammals that evolved in the Eutherian stemlineage, coincident with the evolution of pregnancy, are likely essential for establishment and maintenance of normal pregnancy and are, therefore, good candidates for genes whose expression may be dysregulated in disorders such as REPL. To test this hypothesis, we took an evolutionary forward genomics approach to characterize gene expression profiles of midsecretory endometria from women with REPL associated with abnormal endometria based either on histology or molecular expression of cyclin E. We identified 58 genes that were differentially expressed (P<0.001) between women with out-of-phase histological dating vs normal histology, and 81 genes that were differentially expressed (P<0.001) between women with abnormally elevated cyclin E levels vs normal cyclin E. Remarkably, genes that were recruited into endometrial expression during the evolution of pregnancy in Eutherian mammals were significantly enriched for dysregulated genes (P=0.002 for histology, P=0.021 for cyclin E), as well as for immune and signaling pathways with essential roles in endometrial biology. Thus, our novel evolutionary-based forward genomics approach identified genes whose dysregulation during the mid-secretory phase likely contributes to the molecular etiologies of recurrent early pregnancy loss.
2014-12-06 | GSE63901 | GEO
Project description:The mechanisms controlling genome methylation during human embryogenesis remain largely unknown. Here we provide evidence that maternal age at pregnancy permanently alters the epigenetic profile of offspring. We measured DNA methylation in blood at over 450,000 CpGs across the epigenome in 890 newborns.
2016-06-08 | GSE82273 | GEO