Gestational diabetes exposure induces an altered cardiac transcriptome that is associated with impaired cardiac function in the rat offspring
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE136737 | GEO | 2021/07/31
REPOSITORIES: GEO
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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: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: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:Here we investigated the degree by which epigenetic signatures in children from mothers with obesity or gestational diabetes mellitus are influenced by environmental factors. We profiled the DNA methylation signature of whole blood from lean, obese and gestational diabetes mellitus mothers and their respective newborns. DNA methylation profiles of mothers showed high similarity across groups, while on the contrary, newborns from GDM mothers showed a marked distinct epigenetic profile compared to newborns of both lean and obese mothers. Analysis of variance in DNA methylation levels between newborns showed higher variance in the GDM group. Our work suggest that environmental factors, rather than direct transmission of epigenetic marks from the mother, are involved in establishing the epigenetic signature associated with GDM.
2019-08-22 | GSE128289 | GEO
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
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:Objectives To perceive the temporal features of breast milk proteome between women with gestational diabetes mellitus (GDM) and healthy controls across various lactation periods, as well as to explore the potential impacts of these differences on the growth of offspring.
Methods The study cohort included twenty mothers with GDM and twenty healthy mothers. Human milk samples were obtained at four distinct time points: colostrum (4-6 days postpartum), transitional milk (12-14 days postpartum), early mature milk (42 days postpartum) and mature milk (4 months postpartum). Shotgun proteomics with label free quantification was applied to analyze the milk proteome. Gene Ontology (GO) enrichment analysis, alongside other bioinfomatic tools were conducted to elucidate the function of differentially expressed proteins. Subsequently, a random forest model was utilized to discern proteins that could reliably differentiate milk samples from mothers with gestational diabetes mellitus (GDM) from those of healthy counterparts. Furthermore, correlative analysis was employed to investigate the association between these proteins and the anthropometric indices of infants.
Results Principal coordinate analysis (PCoA) revealed distinct separations in the milk proteome of GDM and healthy mothers during the initial lactation stages, with these differences diminishing over time. The up-regulated proteins in GDM were predominantly associated with the innate immune system, complement and coagulation cascades, cellular secretion, enzymatic and binding activity, and platelet activation. Six proteins were identified as effective markers for distinguishing milk samples from the two groups, with an average area under the curve (AUC) value of 0.91. Twenty-eight proteins exhibited consistent changes between GDM and healthy groups across at least two lactation stages, many of which were significantly correlated to the anthropometric indices of the offsprings.
Conclusions GDM significantly influences the milk proteome, with the extent of alteration diminishing as lactation progresses into the mature milk phase.
| MSV000095983 | MassIVE
Project description:Genomic expression profiles of blood and placenta reveal significant immune-related pathways and categories in Chinese women with Gestational Diabetes Gestational diabetes mellitus (GDM) is a complex metabolic disease which occurs in pregnancy with high prevalence, and its pathogenesis remains elusive. Thus far, there has been no comprehensive gene expression profiling in Chinese women with GDM. In this study, we attempt to define the genes and/or pathways that are involved in GDM with Chinese ethnicity, by the Illumina microarray technique. We found 5,197 and 243 genes with significantly altered expression due to GDM in blood and placenta tissues, respectively. Previously known genes (such as TNF, IL1B, LEP, IFNG, and HLA-G) with altered gene expression in GDM were also validated here. In addition, we identified undescribed genes VAV3, PTPN6, CD48 and IL15, in which expression was related to GDM by microarray and Q-RT-PCR assays. To identify GDM-associated pathways, we used analyses with integrated functional annotation (i.e. KEGG) and extracted two significant pathways, which were Natural killer cell mediated cytotoxicity (hsa04650; FDR = 7.10E-09) in blood and Cytokine-cytokine receptor interaction (hsa04060; FDR = 1.07E-03) in placenta tissues. Immune system process (GO: 0002376) was identified by GO analysis with FDR P-value = 7.01E-60 in blood and FDR P-value = 3.57E-08 in placenta tissues, indicating the importance of immunological and inflammatory categories in GDM. Furthermore, despite differences in the quantity of gene expression, we observed a similar functional distribution between expression of blood and placenta tissues in GDM under the categories of immunity. These newly identified key genes and pathways may provide valuable information for the pathogenesis of GDM and advance disease diagnosis, prevention, medication design, and clinical treatment of the disease. One individual GDM blood tissue sample and one pooled GDM blood tissue sample were compared to one pooled healthy blood tissue sample. One pooled GDM placenta tissue sample was compared to one pooled healthy placenta tissue sample.
2010-12-23 | E-GEOD-19649 | biostudies-arrayexpress
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) 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. RNA extracted from the placentas (maternal-side) of 30 clinically-confirmed cases of GDM and 25 pregnancies without maternal complications was hybridised to the GeneChip® Human Transcriptome Array 2.0 (Affymetrix). Four samples were run in triplicate.
2015-08-03 | E-GEOD-70493 | biostudies-arrayexpress