Perinatal Environmental Exposures: Effects on Metabolic Homeostasis and the Epigenome

Environmental exposures during early development and other critical life stages may induce changes to the epigenome resulting in potentially deleterious phenotypic effects including metabolic disease, cancer, and neurological disorders. The field of epigenetics is experiencing a rapid advancement in technology, methodology, and data acquisition that now allows for the identification of the constellation of genomic loci with altered epigenetic status following dose-dependent exposures. Thus, epigenomic profiling facilitates the identification of biomarkers of exposure, enabling clinicians to identify at-risk individuals prior to disease onset. Utilizing a multi-pronged approach with an in vivo mouse model, human clinical samples, and an ongoing 15-year longitudinal epidemiological study, the overall goal of this presentation is to elucidate the impact of perinatal bisphenol A (BPA) and lead (Pb) exposure on metabolic homeostasis and DNA methylation, and the interplay between the two. Developmental exposure to environmentally relevant levels of BPA has been shown to affect both global and gene-specific DNA methylation patterns in rodents. We now draw upon data from multiple whole-epigenome platforms to show that multiple dose levels of BPA affect DNA methylation in mice and humans and that these epigenetic effects are non-monotonic in dose response. Preliminary studies also indicate that Pb exhibits epigenetic effects that may contribute to its known neurotoxic and obesogenic activities.