Abstract P177: Sex- And Strain- Specific Metabolic Effects Of Postnatal Bpf Exposure In Heterogeneous Stock Rat Founding Inbred Strains

Abstract

Bisphenol F (BPF) is increasing substituting bisphenol A (BPA), an endocrine disruptor associated with cardiometabolic disease, in manufacturing polycarbonates and consumer products. Interindividual variation in bisphenol levels suggests that gene x environment (GxE) interactions influence cardiometabolic disease risk from bisphenol exposure. Studies show that BPF is a potent endocrine disruptor with effects on thyroid, reproductive health, and neuroendocrine functions. Traditional in vivo toxicity studies are performed in isogenic or genetically undefined outbred rodents, leading to conflicting results possibly due to GxE interactions. The N/NIH Heterogeneous Stock (HS) rats are a genetically heterogeneous population amenable to genetic study. Our overall study hypothesis is that BPF-induced cardiometabolic disease has underlying genetic risk, which can be identified using the HS rat and its founding inbred strains. We previously demonstrated that five weeks of postnatal BPF exposure significantly impacts body growth and adiposity in male HS rats. The goal of this project was to evaluate the metabolic health impact of postnatal BPF exposure in HS founding inbred strains. Weanling littermate pairs of male and female ACI/EurMcwi (ACI), BN/NHsdMcwi (BN), F344/Stm (F344), and WKY/NCrl (WKY) rats were randomly exposed to either vehicle (0.1% EtOH) or 1.125 mg BPF/L in 0.1% EtOH for ten weeks in drinking water. Cardiometabolic measures, tissues, urine, and feces were taken. Our studies determined BPF exposure in ACI female rats significantly increased feeding efficiency (0.54 ± 0.07 vs 0.62 ± 0.06 vs, p=0.04), suggesting a possible decrease in metabolic rate. BPF exposure impacted males more often than females, with ACI males showing significantly increased thyroid mass (0.045 ± 0.004 mg/g vs 0.051 ± 0.003 mg/g, p<0.01), BN males showing a trend in increased pituitary mass (0.026 ± 0.003 mg/g vs 0.029 ± 0.001 mg/g, p=0.07), and WKY males showing increased adrenal mass (0.164 ± 0.010 mg/g vs 0.176 ± 0.005 mg/g, p<0.01). Our preliminary data suggests that the ACI strain and male BN and WKY are susceptible to metabolic effects of BPF exposure. This work indicates that the HS rat will be a useful model for dissecting GxBPF interactions on metabolic health.