Genome-wide placental gene methylations in gestational diabetes mellitus, fetal growth and metabolic health biomarkers in cord blood
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PROVIDER: PRJNA825739 | ENA |
REPOSITORIES: ENA
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Project description:Gestational diabetes mellitus (GDM) “program” an elevated risk of metabolic syndrome in the offspring. Epigenetic alterations are a suspected mechanism. GDM has been associated with placental DNA methylation changes in some epigenome-wide association studies. It remains unclear which genes or pathways are affected, and whether any placental differential gene methylations are correlated to fetal growth or circulating metabolic health biomarkers. In an epigenome-wide association study using the Infinium MethylationEPIC Beadchip, we sought to identify genome-wide placental differentially methylated genes and enriched pathways in GDM, and to assess the correlations with fetal growth and metabolic health biomarkers in cord blood. The study samples were 30 pairs of term placentas in GDM vs. euglycemic pregnancies (controls) matched by infant sex and gestational age at delivery in the Shanghai Birth Cohort. Cord blood metabolic health biomarkers included insulin, C-peptide, proinsulin, IGF-I, IGF-II, leptin and adiponectin. Adjusting for maternal age, pre-pregnancy BMI, parity, mode of delivery and placental cell type heterogeneity, 256 differentially methylated positions (DMPs,130 hypermethylated and 126 hypomethylated) were detected between GDM and control groups accounting for multiple tests with false discovery rate <0.05 and beta-value difference >0.05. WSCD2 was identified as a differentially methylated gene in both site- and region-level analyses. We validated 7 hypermethylated (CYP1A2, GFRA1, HDAC4, LIMS2, NAV3, PAX6, UPK1B) and 10 hypomethylated (DPP10, CPLX1, CSMD2, GPR133, NRXN1, PCSK9, PENK, PRDM16, PTPRN2, TNXB) genes reported in previous epigenome-wide association studies. We did not find any enriched pathway accounting for multiple tests. DMPs in 11 genes (CYP2D7P1, PCDHB15, ERG, SIRPB1, DKK2, RAPGEF5, CACNA2D4, PCSK9, TSNARE1, CADM2, KCNAB2) were correlated with birth weight (z score) accounting for multiple tests. There were no significant correlations between placental gene methylations and cord blood biomarkers. In conclusions, GDM was associated with DNA methylation changes in a number of placental genes, but these placental gene methylations were uncorrelated to the observed metabolic health biomarkers (fetal growth factors, leptin and adiponectin) in cord blood. We validated 17 differentially methylated placental genes in GDM, and identified 11 differentially methylated genes relevant to fetal growth.
2022-06-22 | GSE200659 | GEO
Project description:Gestational diabetes mellitus alters placental structure, efficiency, and plasticity
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Project description:The hemochorial placenta provides a critical barrier at the maternal-fetal interface to modulate maternal immune tolerance and enable gas and nutrient exchange between mother and conceptus. Pregnancy outcomes are adversely affected by gestational diabetes mellitus (GDM); however, the effects of GDM on placental formation, and subsequently fetal development, are not fully understood. In this report, streptozotocin was used to induce hyperglycemia in pregnant rats for the purpose of investigating the impact of GDM on placental formation and fetal development. GDM caused placentomegaly and placenta malformation, decreasing placental efficiency and fetal size. Elevated glucose disrupted rat trophoblast stem (TS) cell differentiation in vitro. Evidence of altered trophoblast differentiation was also observed in vivo, as hyperglycemia affected the junctional zone transcriptome and interfered with intrauterine trophoblast invasion and uterine spiral artery remodeling. When exposed to hypoxia, rats with GDM showed decreased proliferation and ectoplacental cone development on gestation day (gd) 9.5 and complete pregnancy loss by gd 13.5. Furthermore, elevated glucose concentrations inhibited TS cell responses to hypoxia in vitro. Overall, these results indicate that alterations in placental development, efficiency, and plasticity could contribute to the suboptimal fetal outcomes in offspring from pregnancies complicated by GDM.
2020-07-07 | GSE144276 | GEO
Project description:The objective of this study was to investigate whether placental exosomes in gestational diabetes mellitus (GDM) carries a specific set of miRNAs associated with skeletal muscle insulin sensitivity. Exosomes were isolated from chorionic villi-conditioned media and plasma from normal and GDM pregnancies. A specific set of miRNAs was identified to be selectively enriched within exosomes when compared to their cells of origin indicating specific packaging of miRNAs into exosomes. In addition, miRNA expression varies in a consistent pattern in placenta, placental-derived exosomes, circulating exosomes and skeletal muscle in GDM.
2021-03-20 | GSE112168 | GEO
Project description:This study aims to identify genome-wide placental DNA differential methylation positions (DMPs) in fetal overgrowth and the associations with fetal growth factors, leptin and adiponectin. In the Shanghai Birth Cohort, we studied 30 pairs of placentals of large-for-gestational-age (LGA, birth weight>90th percentile, an indicator of fetal overgrowth) and optimal-for-gestational-age (OGA, 25th-75th percentiles, control) newborns matched by sex and gestational age. Placental DNA methylations were measured by the Illumina Infinium Human Methylation-EPIC BeadChip. Cord blood insulin, C-peptide, proinsulin, IGF-1, IGF-2, leptin and adiponectin concentrations were measured. We identified 543 DMPs (397 hypermethylated, 146 hypomethylated) comparing LGA vs. OGA at false discovery rate <5% and absolute methylation difference >0.05 adjusting for placental cell type heterogeneity, maternal age, pre-pregnancy BMI and HbA1c levels during pregnancy. We validated a hyper-methylated gene - cadherin 13 (CDH13) reported in a previous epigenome-wide association study, and validated a newly discovered differentially (hyper-)methylated gene -visual system homeobox 1 (VSX1) in an independent pyrosequencing study sample (47 LGA-control pairs). Pathway analysis did not detect any statistically significant pathway correcting for multiple tests. Adiponectin in cord blood was correlated with its gene methylation in the placenta, while other observed biomarkers were not. Fetal overgrowth was associated with a large number of altered placental gene DNA methylations. The study provides robust evidence suggesting that placental CDH13 and VSX1 genes are hyper-methylated in LGA. Placental gene methylation was correlated with cord blood biomarker for adiponectin, but not for leptin and fetal growth factors.
2022-12-31 | GSE204977 | GEO
Project description:Gestational diabetes mellitus (GDM), one of the most common pregnancy complications, affects approximately 6% of pregnancies. This study attempted to use the data-independent acquisition (DIA) mass spectrometry (MS) to identify the potential protein biomarkers from the placental tissues from the GDM patients and the normal pregnant women.
2021-12-28 | PXD030656 |
Project description:Gestational diabetes mellitus (GDM) "program" an elevated risk of metabolic syndrome in the offspring. Epigenetic alterations are a suspected mechanism. GDM has been associated with placental DNA methylation changes in some epigenome-wide association studies. It remains unclear which genes or pathways are affected, and whether any placental differential gene methylations are correlated to fetal growth or circulating metabolic health biomarkers. In an epigenome-wide association study using the Infinium MethylationEPIC Beadchip, we sought to identify genome-wide placental differentially methylated genes and enriched pathways in GDM, and to assess the correlations with fetal growth and metabolic health biomarkers in cord blood. The study samples were 30 pairs of term placentas in GDM vs. euglycemic pregnancies (controls) matched by infant sex and gestational age at delivery in the Shanghai Birth Cohort. Cord blood metabolic health biomarkers included insulin, C-peptide, proinsulin, IGF-I, IGF-II, leptin and adiponectin. Adjusting for maternal age, pre-pregnancy BMI, parity, mode of delivery and placental cell type heterogeneity, 256 differentially methylated positions (DMPs,130 hypermethylated and 126 hypomethylated) were detected between GDM and control groups accounting for multiple tests with false discovery rate <0.05 and beta-value difference >0.05. WSCD2 was identified as a differentially methylated gene in both site- and region-level analyses. We validated 7 hypermethylated (CYP1A2, GFRA1, HDAC4, LIMS2, NAV3, PAX6, UPK1B) and 10 hypomethylated (DPP10, CPLX1, CSMD2, GPR133, NRXN1, PCSK9, PENK, PRDM16, PTPRN2, TNXB) genes reported in previous epigenome-wide association studies. We did not find any enriched pathway accounting for multiple tests. DMPs in 11 genes (CYP2D7P1, PCDHB15, ERG, SIRPB1, DKK2, RAPGEF5, CACNA2D4, PCSK9, TSNARE1, CADM2, KCNAB2) were correlated with birth weight (z score) accounting for multiple tests. There were no significant correlations between placental gene methylations and cord blood biomarkers. In conclusions, GDM was associated with DNA methylation changes in a number of placental genes, but these placental gene methylations were uncorrelated to the observed metabolic health biomarkers (fetal growth factors, leptin and adiponectin) in cord blood. We validated 17 differentially methylated placental genes in GDM, and identified 11 differentially methylated genes relevant to fetal growth.
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Project description:DNA methylation and gestational diabetes mellitus
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Project description:tsRNA profiles of gestational diabetes mellitus and healthy control groups were generated by deep sequencing using Illumina NextSeq 500.
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Project description:The oligo microarray were used to determine gene expression profile of PBMC from gestational diabetes mellitus (GDM) patients.
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