Effects of GDM involves alterations in gene specific DNA methylation
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE65779 | GEO | 2015/02/10
SECONDARY ACCESSION(S): PRJNA274993
REPOSITORIES: GEO
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Project description:Gestational diabetes mellitus(GDM) will bring health issues for offspring. The offspring of diabetic mothers often reveal high birth weight and are prone to have obesity, hypertension and dyslipidemia. It was implied that the phenotype of offspring might be influenced by intrauterine environment and planned in utero already in addition to the genetic influences.M-bM-^@M-^XProgrammingM-bM-^@M-^Y refers to the process whereby a stimulus at a critical window of development has long-term effects. A large body of studies investigated the adverse intrauterine environment was correlated with poor fetal growth and increased risk of Type 2 diabetes in the adulthood. Epigenetic mechanism has been proposed to involve in the link between environmental and nutritional factors and gene expression regulation. DNA methylation is one of the major epigenetic modifications. We hypothesized that DNA methylation changes could participate in the gene expression related to glucose intolerance in the offspring. Furthermore, DNA methylation might also determine the transgenerational disease transmission. comparison of intrauterine hyperglycemia exposed rats vs. control rats for genome-wide DNA methylation changes
2015-02-10 | E-GEOD-65779 | biostudies-arrayexpress
Project description:Objective: To explore the characteristics and underlying molecular mechanisms of genome-scale expression profiles of women with- or without- gestational diabetes mellitus and their offspring. Materials and Methods: We recruited a group of 21 pregnant women with gestational diabetes mellitus (GDM) and 20 healthy pregnant women as controls. For each pregnant women, RRBS were performed using the placenta and paired neonatal umbilical cord blood specimens. Differentially methylated regions (DMRs) were identified. Then, functional enrichment analysis was performed to differential methylated genes (DMGs) separately or interactively in placenta and umbilical cord blood. Results: Through the comparison of GDM and healthy samples, 2779 and 141 DMRs were identified from placenta and umbilical cord blood, respectively. Functional enrichment analysis showed that the placenta methylation and expression profiles of GDM women mirrored the molecular characteristics of “type II diabetes” and “insulin resistance”. Methylation-altered genes in umbilical cord blood were associated with pathways “type II diabetes” and “cholesterol metabolism”. DMGs illustrated significant overlaps among placenta and umbilical cord blood samples, and the overlapping DMGs were associated with cholesterol metabolism. Conclusions: Our research demonstrated the epigenomic alternations of GDM mothers and offspring. Our findings emphasized the importance of epigenetic modifications in the communication between pregnant women with GDM and offspring, and provided reference for the prevention, control, treatment, and intervention of perinatal deleterious events of GDM and neonatal complications.
2022-05-31 | GSE203169 | GEO
Project description:Studies on human and animals suggest associations between gestational diabetes mellitus (GDM) with impaired cognitive performance in offspring. Using a mouse model of diabetes during pregnancy, we found that intrauterine hyperglycemia exposure resulted in memory impairment in both the first filial (F1) males and the second filial (F2) males from the F1 male offspring. The effects of intrauterine hyperglycemia exposure on F1 and F2 hippocampus gene expression were also examined.
2021-08-25 | GSE147039 | GEO
Project description:The prevalence of metabolic syndrome comprising obesity, type 2 diabetes mellitus and cardiovascular disease has been on the rise world-wide in recent years. As non-communicable diseases such as type 2 diabetes mellitus have their roots in prenatal development and conditions such as maternal gestational diabetes (GDM), we aimed to test this hypothesis in primary cells derived from the offspring of GDM mothers compared to control subjects. Methods We have assessed primary umbilical cord derived cells such as human vascular endothelial cells (HUVECs) and Wharton’s jelly derived mesenchymal stem cells (WJMSCs) from both, the offspring of GDM and healthy mothers. We have compared the primary isolates in cell based assays measuring proliferation, mitochondrial oxygen consumption, as well as the ability to support blood vessel growth. We conducted gene expression microarray studies with subsequent pathway analysis and candidate gene validation. Results We observed striking differences between the two groups such as lower metabolic rates and impairment of tube formation in cells with GDM background. HUVECs from subjects with maternal GDM have lower expression of the anti-apoptotic protein BCL-Xl suggesting compromised angiogenic capabilities. Comparative gene expression analysis revealed blood vessel formation as a major pathway enriched in the GDM derived HUVECs with the surface marker CD44 as a significant gene under-expressed in the GDM group. Functional validation of CD44 revealed that it regulates tube formation in HUVECs thereby providing new insights into a novel pathway imprinted in primary umbilical cord derived cells from GDM offspring. Conclusions/interpretation Our data demonstrate that primary cells isolated from the umbilical cord of offspring born to GDM mothers maintain metabolic and molecular imprints of maternal hyperglycemia, which occurred during prenatal development reflecting an enhanced risk for cardiovascular disease later in life.
2016-09-24 | GSE87295 | GEO
Project description:Objective: To explore the characteristics and underlying molecular mechanisms of genome-scale expression profiles of women with- or without- GDM and their offspring. Materials and Methods: We recruited a group of 21 pregnant women with GDM and 20 healthy pregnant women as controls. For each pregnant women, RNA-seq were performed using the placenta and paired neonatal umbilical cord blood specimens. Differentially expressed genes (DEGs) were identified with BMI of pregnant women as covariates. Then, functional enrichment analysis was performed separately or interactively in placenta and umbilical cord blood. Results: Through the comparison of GDM and healthy samples, 1442 and 488 DEGs were identified from placenta and umbilical cord blood, respectively. Functional enrichment analysis showed that the placenta expression profiles of GDM women mirrored the molecular characteristics of type II diabetes and insulin resistance patients. DEGs illustrated significant overlaps among placenta and umbilical cord blood samples, and the overlapping DEGs were associated with endocrine resistance and insulin resistance. Conclusions: Our research demonstrated the transcriptomic alternations of GDM mothers and offspring. Our findings emphasized the importance of epigenetic modifications in the communication between pregnant women with GDM and offspring, and provided reference for the prevention, control, treatment, and intervention of perinatal deleterious events of GDM and neonatal complications.
2022-05-31 | GSE203346 | GEO
Project description:Intrauterine hyperglycemia has been linked to an elevated risk of diabetes in next and further generations. Existing reports about transmission effects of intrauterine hyperglycemia have included both intrauterine and postnatal metabolic exposure factors, the impact of intrauterine hyperglycemia per se has not been separately assessed. To investigate effect of intrauterine hyperglycemia exposure per se on further generations, we selected non-phenotypic F1-GDM and F2-GDM male mice to examin metabolic changes in next generation and performed a methylome on day 13.5 primordial germ cells (PGCs) of F1-GDM male fetus to explore its underlying mechanism. We found that intrauterine hyperglycemia exposure per se resulted in obesity, insulin resistance and/or glucose intolerance in F2 male mice, and no changes in F3 male mice. Methylome of day 13.5 PGCs of F1-GDM male fetus revealed differently methylation genes enriched in obesity and diabetic pathogenesis. Methylation validation of targeted gene Fyn showed consistent hypo-methylation status in F1 PGCs, F1 fetal testis, sperm of F1/N-GDM mice, and somatic cells of F2-GDM male mice. While fetal testis of F2-GDM mice showed no alteration in Fyn methylation. Our data indicates that intrauterine hyperglycemia exposure per se contributes to metabolic changes in F2 but not F3 generation, by altering methylation erasure in PGCs of F1 generation.
2017-12-20 | GSE108319 | GEO
Project description:Context: Context: Gestational diabetes (GDM) has profound effects on the intrauterine metabolic milieu and is linked to obesity and diabetes in offspring, but the mechanisms driving these effects remain largely unknown. Alterations gene expression in amniocytes exposed to GDM in utero may identify potential mechanisms leading to metabolic dysfunction later in life. Objective: Objective: To profile changes in the transcriptome in human amniocytes exposed to GDM Methods: A nested case-control study was performed in second trimeseter amniocytes matched for offspring sex, maternal race/ethnicity, maternal age, gestational age at amniocentesis, gestational age at birth and gestational diabetes status. Sex-specific RNA-sequencing was completed and gene expression changes were identified. Results: Expression of interferon-stimulated genes was increased in GDM amniocytes accounting for 6 of the top 10 altered genes (q<0.05). Enriched biological pathways in GDM anmiocytes included pathways involving inflammation, the interferon response, fatty liver disease, monogenic diabetes and atherosclerosis. Conclusion: In a unique repository of human amniocytes exposed to GDM in utero, trancriptome analysis identified enrichment of inflammation and interferon-related pathways.
2020-05-15 | GSE150621 | GEO
Project description:Background: Intrauterine exposure to gestational diabetes mellitus (GDM) confers a lifelong increased risk for metabolic and other complex disorders to the offspring. GDM-induced epigenetic modifications modulating gene regulation and persisting into later life are generally assumed to mediate these increased disease risks. To identify candidate genes for fetal programming, we compared genome-wide methylation patterns of fetal cord bloods (FCBs) from GDM and control pregnancies. Methods and Results: Using Illumina's 450K methylation arrays and following correction for multiple testing, 65 CpG sites (52 of which are associated with genes) displayed significant methylation differences between GDM and control samples. Three of four candidate genes, ATP5A1, PRKCH, and SLC17A4, from our methylation screen and one, HIF3A, from the literature were validated by bisulfite pyrosequencing. The GDM effect on FCB methylation was more pronounced in women with insulin-dependent GDM who had a more severe metabolic phenotype than women with dietetically treated GDM. However, the effect remained significant after adjustment for the maternal BMI and gestational week in a multivariate regression model. Conclusions: Our study supports an association between maternal GDM and the epigenetic status of the exposed offspring. Consistent with a multifactorial disease model, the observed FCB methylation changes are of small effect size but affect multiple genes/loci. The identified genes are primary candidates for transmitting GDM effects to the next generation. They also may provide useful biomarkers for the diagnosis and prognosis of adverse prenatal exposures and assessing the success of interventions during pregnancy.
2017-03-29 | GSE88929 | GEO
Project description:Gestational diabetes mellitus (GDM) affects approximately 18% of pregnancies in the United States and increases the risk of adverse health outcomes in the offspring. These adult disease propensities may be set by anatomical and molecular alterations in the placenta associated with GDM. To assess the mechanistic aspects of fetal programming, we measured genome-wide methylation (Infinium HumanMethylation450 Beadchips) and expression (Affymetrix Transcriptome Microarrays) in placental tissue of 41 GDM cases and 41 matched pregnancies without maternal complications from the Harvard Epigenetic Birth Cohort. Specific transcriptional and epigenetic perturbations associated with GDM status included alterations in the major histocompatibility complex (MHC) region, which were validated in an independent cohort, the Rhode Island Child Health Study. Gene ontology enrichment among gene regulation influenced by GDM revealed an over-representation of immune response pathways among differential expression, reflecting these coordinated changes in the MHC region. Our study represents the largest investigation of transcriptomic and methylomic differences associated with GDM, providing comprehensive insight into the molecular basis of GDM induced fetal (re)programming. Bisulphite converted DNA extracted from the placentas (maternal-side) of 41 clinically-confirmed cases of GDM and 41 pregnancies without maternal complications were hybridised to the Illumina Infinium HumanMethylation450 Beadchips
2015-08-03 | E-GEOD-70453 | biostudies-arrayexpress
Project description:Gestational diabetes mellitus (GDM) exposure and obesity are strong risk factors for type 2 diabetes development; however, the connections between GDM exposure, postnatal diet and islet dysfunction in offspring metabolic health remain unclear. Reduced glucose-stimulated insulin secretion was observed in islets isolated from 15-week-old offspring prenatally exposed to GDM, which was exacerbated by postnatal HFS consumption. In the HFS-fed offspring of Lean dams, islet size and number increased, an adaptation that was not observed in the HFS-fed offspring of GDM dams. Islets from GDM exposed offspring revealed upregulation of 102 genes (e.g. Sod2, Il1b) and 13 downregulated genes. In the GDM offspring that consumed a postnatal HFS-diet, 126 genes were significantly upregulated (e.g. Ccl2, Rps14, Atp5f1) and 17 genes were downregulated (e.g. Hnf1a, Slc2a2). These results demonstrate that GDM exposure induced changes in gene expression in the young adult rat offspring that worsen islet function and whole-body glucose homeostasis.
2019-12-31 | GSE116663 | GEO