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

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 (50 μg/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.