Valerie A Wagner, Katie L Holl, Karen C Clark, John J Reho, Melinda R Dwinell, Hans-Joachim Lehmler, Hershel Raff, Justin L Grobe, Anne E Kwitek

Environmental bisphenol compounds like bisphenol F (BPF) are endocrine disrupting chemicals (EDC) affecting adipose and classical endocrine systems. Genetic factors that influence EDC exposure outcomes are poorly understood and are unaccounted variables that may contribute to the large range of reported outcomes in the human population. We previously demonstrated that BPF exposure increased body growth and adiposity in male N/NIH Heterogeneous Stock (HS) rats, a genetically heterogeneous outbred population. We hypothesize that the founder strains of the HS rat exhibit EDC effects that were strain- and sex-dependent. Weanling littermate pairs of male and female ACI, BN, BUF, F344, M520, and WKY rats randomly received either vehicle (0.1% EtOH) or 1.125 mg BPF/L in 0.1% EtOH for ten weeks in drinking water. Body weight and fluid intake were measured weekly, metabolic parameters were assessed, and blood and tissues were collected. BPF increased thyroid weight in ACI males, thymus and kidney weight in BUF females, adrenal weight in WKY males, and possibly increased pituitary weight in BN males. BUF females also developed a disruption in activity and metabolic rate with BPF exposure. These sex- and strain-specific exposure outcomes illustrate that HS rat founders possess diverse bisphenol-exposure risk alleles and suggests that BPF exposure may intensify inherent organ system dysfunction existing in the HS rat founders. We propose that the HS rat will be an invaluable model for dissecting gene EDC interactions on health.