Human Feto-placental Arterial and Venous Endothelial Cells are Differentially Programmed by Gestational Diabetes Mellitus Resulting in Cell-specific Barrier Function Changes

We performed genome-wide methylation analysis of primary feto-placental arterial and venous endothelial cells from healthy (AEC and VEC) and GDM complicated pregnancies (dAEC and dVEC). Parallel transcriptome analysis identified variation in gene expression linked to GDM-associated DNA methylation, implying a direct functional link. Pathway analysis found that genes altered by exposure to GDM clustered to functions associated with ’Cell Morphology’ and ’Cellular Movement’ in both AEC and VEC. Further functional analysis demonstrated that GDM exposed cells have altered actin organization and barrier function. Our data indicate that exposure to GDM programs atypical morphology and barrier function in feto-placental endothelial cells by DNA methylation and gene expression change. The effects differ between AEC and VEC, indicating a stringent cell-specific sensitivity to adverse exposures associated with developmental programming in utero. Primary human feto-placental endothelial cells form arteries (AEC) and veins (VEC) were isolated after healthy pregnancy (AEC, VEC) and after a pregnancy complicated by Gestational Diabetes Mellitus (dAEC, dVEC). Total RNA was isolated and subjected to microarray analysis.