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Reduced representation bisulfite sequencing (RRBS) methylation profiles of placenta and umbilical cord blood with or without gestational diabetes mellitus (GDM)

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE203169 | GEO | 2022/05/31

REPOSITORIES: GEO

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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.

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.

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Reduced representation bisulfite sequencing (RRBS) methylation profiles of placenta and umbilical cord blood with or without gestational diabetes mellitus (GDM)

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