Lineage and life history: Synchronicity of ancestral vinclozolin exposure and adolescent stress on gene expression and global methylation patterns

Endocrine-disrupting chemicals (EDCs) are compounds that alter normal endocrine function. EDCs are subject to bioaccumulation due to their inherent stability. The body burden of EDCs in animal populations poses an evolutionary threat, as epigenetic modifications to germ line cells affect subsequent generations. Vinclozolin is an anti-androgenic EDC that is used in the agricultural industry as a fungicide. Prenatal vinclozolin exposure leads to a variety of disease states that proliferate through the germ line. In the current study, I combined a germline-dependent epigenetic modification, vinclozolin exposure administered 3 generations previously, with a context-dependent epigenetic modification, chronic restraint stress (CRS) during adolescence of the F3 generation. The combination of these two epigenetic modifications allows for a better recreation of real world events experienced by animals. The expression of 48 genes across six brain nuclei was analyzed using real-time PCR on Taqman Low Density Arrays (TLDAs) in male adult rats. Global methylation levels were analyzed using 5-methylCytosine ELISA assays for all six nuclei. Vinclozolin and CRS led to unique gene expression and global methylation patterns seen in essential nuclei to the neural circuits modulating the stress response, sexual behavior, and physiology. When compared to control, nonstressed animals, individuals exposed to both treatments display a unique phenotype distinct from either of the treatments alone.