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Epigenome analysis of cord blood DNA from infants born into the UPBEAT study

ABSTRACT: Genome-wide DNA methylation profiling of umbilical cord blood buffy coat DNA samples. The Illumina Infinium MethylationEPIC array was used to obtain DNA methylation profiles across approximately 850,000 CpGs. Samples included 557 cord blood samples born to obese women in the UPBEAT trial, with and without gestational diabetes mellitus (GDM), to determine the association between maternal GDM and hyperglycaemia during pregnancy on the methylation in the infant.

ORGANISM(S): Homo sapiens

PROVIDER: GSE141065 | GEO | 2020/11/05

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.

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Epigenome analysis of cord blood DNA from infants born into the UPBEAT study

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