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: 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.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.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.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
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