Abstract: PP27-4

Intrauterine Exposure to Maternal Diabetes Alters DNA Methylome Profiling in Fetal Vascular Endothelial Cells

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Abstract


Epidemiological and animal studies have illustrated that abnormal intrauterine environment of Gestational diabetes mellitus (GDM) has long-term adverse impacts on the cardiovascular system of GDM children and adolescents. Endothelial cells, function as primary regulator and effector in cardiovascular dysfunction, are good candidates for studying the pathogenesis of vascular dysfunction in GDM offspring. view more

Epidemiological and animal studies have illustrated that abnormal intrauterine environment of Gestational diabetes mellitus (GDM) has long-term adverse impacts on the cardiovascular system of GDM children and adolescents. Endothelial cells, function as primary regulator and effector in cardiovascular dysfunction, are good candidates for studying the pathogenesis of vascular dysfunction in GDM offspring. The purpose of the present study was to perform a genome-wide analysis of the DNA methylation profile to evaluate the epigenetic change of endothelial cells in GDM offspring and the potential mechanisms as well as the impacts on the cardiovascular system. Primary endothelial cells from human umbilical veins of 6 GDM and 6 matched normal pregnancies were used for Illumina Human Methylation 450k BeadChip assays. A total of 3,363 differentially methylated sites (p<0.01) were revealed between the two groups. After validating the microarray results, differentially methylated genes were analyzed by bioinformatics and the Ingenuity Pathway Analysis (IPA) software. Functional analysis indicated that the differential genes of endothelial cells from GDM offspring are significantly enriched in cell-cell adhesion, cell migration and vasculogenesis. Differential methylation of STAB2,WASF2,FOXF1 and BMP7 were involved in endothelial cell impairment of GDM offspring.The functional characteristics were assessed by transwell with primary human endothylial cells from 25 GDM and 25 normal pregnancies.And the impairment of cell migration and cell proliferation were found in GDM. This is the first research about the genome-wide DNA methylation profile analysis of primary endothelial cells of human umbilical vein of GDM offspring. Our data and phenotypic results figured out that the children exposed to abnormal environment of GDM might display vascular endothelium dysfunction by DNA methylation alterations.The impaired endothelial cell migration under hypoxia could be one of the potential mechanisms.

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