Adverse Maternal Metabolic Intrauterine Environment and Placental Epigenetics: Implications for Fetal Metabolic Programming.

Abstract

Herein, we summarize existent epidemiological studies relating adverse maternal metabolic environments of maternal obesity and gestational diabetes and placental DNA methylation. Multiple studies have evaluated associations between intrauterine exposure to gestational diabetes and/or maternal glucose levels and DNA methylation at candidate metabolic genes as well as in epigenome-wide studies. Some of the genomic regions more consistently associated include lipid-related genes (LPL and PPARGC1A), the major histocompatibility complex (MHC), and imprinted genes. Studies solely focused on maternal obesity influences on the placental epigenome are scarce. Understanding the placental mechanisms involved in fetal metabolic programming could lead to discovery of placental biomarkers at birth that predict later-life metabolic risk. Moving forward is important to standardize methods utilized in epigenetics research; consistent methodology can help interpret disparate findings. Larger studies with longitudinal follow-up are needed to address future challenges in fetal programming research.