Longitudinal effects of developmental bisphenol A and variable diet exposures on epigenetic drift in mice

Reprod Toxicol. 2017 Mar:68:154-163. doi: 10.1016/j.reprotox.2016.07.021. Epub 2016 Aug 2.

Abstract

Environmental factors, including exogenous exposures and nutritional status, can affect DNA methylation across the epigenome, but effects of exposures on age-dependent epigenetic drift remain unclear. Here, we tested the hypothesis that early-life exposure to bisphenol A (BPA) and/or variable diet results in altered epigenetic drift, as measured longitudinally via target loci methylation in paired mouse tail tissue (3 wks/10 mos old). Methylation was quantified at two repetitive elements (LINE-1, IAP), two imprinted genes (Igf2, H19), and one non-imprinted gene (Esr1) in isogenic mice developmentally exposed to Control, Control+BPA (50μg/kg diet), Mediterranean, Western, Mediterranean+BPA, or Western+BPA diets. Across age, methylation levels significantly (p<0.050) decreased at LINE-1, IAP, and H19, and increased at Esr1. Igf2 demonstrated Western-specific changes in early-life methylation (p=0.027), and IAP showed marginal negative modification of drift in Western (p=0.058) and Western+BPA (p=0.051). Thus, DNA methylation drifts across age, and developmental nutritional exposures can alter age-related methylation patterns.

Keywords: Bisphenol A; DNA methylation; Developmental origins of health and disease; Drift; Epigenetics; High fat diet.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds / toxicity*
  • DNA Methylation / drug effects*
  • Diet*
  • Environmental Pollutants / toxicity*
  • Epigenesis, Genetic / drug effects*
  • Female
  • Mice
  • Nutritional Status
  • Phenols / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Prenatal Exposure Delayed Effects / genetics
  • Time Factors

Substances

  • Benzhydryl Compounds
  • Environmental Pollutants
  • Phenols
  • bisphenol A