104 Epigenetic Changes Due to Environmental Toxicants: An Animal Health Concern

Abstract

Abstract Endocrine disrupting chemicals (EDCs) mimic natural hormones in the body, but they are not subject to normal homeostatic regulatory mechanisms. One such EDC that is particularly important in animal and human health is bisphenol A (BPA) that is an industrial chemical used to harden plastic, and thus, it is prevalent in many common household items. Notably, BPA, and likely other EDCs, persist in the environment. Besides binding to steroid and non-steroid receptors, BPA and other EDCs may induce epigenetic changes directly or by affecting gut bacteria that can promote such host changes. The objective of current studies was to determine whether developmental exposure to BPA and/or genistein, a phytoestrogen, induce persistent epigenetic and transcriptomic changes in various brain regions and the placenta. Additionally, the ability of these chemicals to alter gut microbiota and gut metabolites that may trigger such epigenetic alterations were investigated. Animal models used to examine for such effects included California mice (Peromyscus californicus), deer mice (Peromyscus maniculatus), laboratory mice (Mus musculus), and eastern painted turtles (Chrysemys picta). To link these ‘omics changes to actual phenotypic modifications, several behavioral domains were assessed in these species following developmental exposure to these compounds. Results across taxa clearly show that BPA and genistein leads to behavioral deficits, including cognitive and social impairments, anxiogenic behaviors, and reduced voluntary physical activity. Correspondingly, both chemicals transformed the epigenome and transcriptome in key brain regions and the placenta. Gut dysbiosis and stimulation of harmful bacterial metabolites ensued following early EDC exposure, and such effects persisted through adulthood. By using a one health medicine approached that evaluated various vertebrate animal species, there is solid evidence that perinatal exposure to BPA and genistein reprograms the epigenome and thereby lead to longstanding health consequences. Such findings have important veterinary and human health ramifications.