Associations between Early Pregnancy Maternal Body Mass Index (BMI) and Offspring Sex with Placental DNA Methylation at Term

Abstract

BackgroundThe placenta serves as the definitive maternal‐fetal interface and mediates exchange of nutrients, gases, and waste between mother and the developing fetus. The placenta integrates signals from both mother and baby, coordinating maternal nutrient supply with fetal demand and development. In epidemiological studies, maternal obesity and obesogenic diets are associated with fetal overgrowth and greater risk of obesity and metabolic dysfunction in later‐life. Animal and human studies have shown maternal obesity‐associated alterations in placental gene expression, as well as sex‐dependent structural and functional placental differences. Whether maternal obesity and offspring sex are important contributors to placental epigenetic alterations is yet to be determined.HypothesisWe hypothesized that placental epigenetic patterns are associated with maternal early pregnancy body composition (BMI or percent body fat) and offspring sex.MethodsUsing Reduced Representation Bisulfite Sequencing (RRBS), we assessed genome scale DNA methylation at approximately 300,000 CpGs in 150 placenta from uncomplicated full‐term pregnancies (N=72 normal weight mothers, N=78 overweight/obese mothers). Maternal BMI and percent body fat were assessed at <10 weeks of gestation.ResultsIn multivariable linear regression models adjusted for multiple testing (q<0.2) and covariates (maternal age at delivery, infant sex, and delivery mode), maternal early pregnancy BMI was significantly associated with placental DNA methylation of 54 specific CpGs while maternal early pregnancy body fat percentage was significantly associated with methylation of 1 CpG. Likewise, in multivariable linear regression, male infant sex was significantly associated with methylation of 34 specific CpGs. Of the 54 CpGs significantly associated with maternal early pregnancy BMI, gene‐set enrichment analysis of the proximal genes associated with these differentially‐methylated CpGs showed biological processes related to lipid metabolism, DNA repair, and vesicle exocytosis to be differentially methylated. Of the 34 CpGs significantly associated with male offspring sex, gene‐set enrichment analysis of the proximal genes associated with these differentially‐methylated CpGs showed biological processes related to corticotropin secretion and protein localization to the nucleolus to be differentially methylated.ConclusionsThese data suggest that maternal obesity, as assessed by early pregnancy BMI, and male offspring sex have modest but unique effects on placental DNA methylation patterns.Support or Funding InformationThis work was supported by USDA ARIS Project 6026‐51000‐010‐05S.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.