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Title: Offspring sex impacts DNA methylation and gene expression in placentae from women with diabetes during pregnancy.

Authors: Alexander, Jacqueline; Teague, April M; Chen, Jing; Aston, Christopher E; Leung, Yuet-Kin; Chernausek, Steven; Simmons, Rebecca A; Pinney, Sara E

Published In PLoS One, (2018)

Abstract: AIMS/HYPOTHESIS: We hypothesized that diabetes during pregnancy (DDP) alters genome-wide DNA methylation in placenta resulting in differentially methylated loci of metabolically relevant genes and downstream changes in RNA and protein expression. METHODS: We mapped genome-wide DNA methylation with the Infinium 450K Human Methylation Bead Chip in term fetal placentae from Native American and Hispanic women with DDP using a nested case-control design (n = 17 pairs). RNA expression and protein levels were assayed via RNA-Seq and Western Blot. RESULTS: Genome-wide DNA methylation analysis revealed 465 CpG sites with significant changes for male offspring, 247 for female offspring, and 277 for offspring of both sexes (p<0.001). Placentae from female offspring were 40% more likely to have significant gains in DNA methylation compared with placentae from male offspring exposed to DDP (p<0.001). Changes in DNA methylation corresponded to changes in RNA and protein levels for 6 genes: PIWIL3, CYBA, GSTM1, GSTM5, KCNE1 and NXN. Differential DNA methylation was detected at loci related to mitochondrial function, DNA repair, inflammation, oxidative stress. CONCLUSIONS/INTERPRETATION: These findings begin to explain mechanisms responsible for the increased risk for obesity and type 2 diabetes in offspring of mothers with DDP.

PubMed ID: 29470513 Exiting the NIEHS site

MeSH Terms: Adult; Case-Control Studies; CpG Islands; DNA Methylation*; Diabetes Mellitus, Type 2/etiology; Female; Gene Expression*; Humans; Infant, Newborn; Male; Obesity/etiology; Placenta/metabolism*; Pregnancy; Pregnancy in Diabetics/genetics*; Pregnancy in Diabetics/metabolism*; Prenatal Exposure Delayed Effects/genetics; Prenatal Exposure Delayed Effects/metabolism; RNA, Messenger/genetics; RNA, Messenger/metabolism; Sex Factors; Young Adult

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