差异甲基化区
DNA甲基化
生物
内分泌学
妊娠期糖尿病
表观遗传学
内科学
后代
遗传学
基因
基因表达
怀孕
医学
妊娠期
作者
Sara E. Pinney,Apoorva Joshi,Victoria Yin,So Won Min,Cetewayo S. Rashid,David E. Condon,Paul Zhipang Wang
标识
DOI:10.1210/clinem/dgaa466
摘要
Abstract Context Gestational diabetes (GDM) has profound effects on the intrauterine metabolic milieu and is linked to obesity and diabetes in offspring, but the mechanisms driving these effects remain largely unknown. Alterations in DNA methylation and gene expression in amniocytes exposed to GDM in utero represent a potential mechanism leading to metabolic dysfunction later in life. Objective To profile changes in genome-wide DNA methylation and expression in human amniocytes exposed to GDM. Design A nested case-control study (n = 14 pairs) was performed in amniocytes matched for offspring sex, maternal race/ethnicity, maternal age, gestational age at amniocentesis, and gestational age at birth. Sex-specific genome-wide DNA methylation analysis and RNA-sequencing were completed and differentially methylated regions (DMRs) and gene expression changes were identified. Ingenuity pathway analysis identified biologically relevant pathways enriched after GDM exposure. In silico high-throughput chromosome conformation capture (Hi-C) analysis identified potential chromatin interactions with DMRs. Results Expression of interferon-stimulated genes was increased in GDM amniocytes, accounting for 6 of the top 10 altered genes (q < 0.05). Enriched biological pathways in GDM amniocytes included pathways involving inflammation, the interferon response, fatty liver disease, monogenic diabetes, and atherosclerosis. Forty-two DMRs were identified in male GDM-exposed amniocytes and 20 in female amniocyte analysis (q < 0.05). Hi-C analysis identified interactions between DMRs and 11 genes with significant expression changes in male amniocytes and 9 in female amniocytes (P < .05). Conclusion In a unique repository of human amniocytes exposed to GDM in utero, transcriptome analysis identified enrichment of inflammation and interferon-related pathways and novel DMRs with potential distal regulatory functions.
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