Immune, metabolic, and renal effects of post-wean BPF exposure in BUF/Mna female rats

Exposure to endocrine-disrupting chemicals (EDCs) increases the risk of obesity and related cardiometabolic disorders. Bisphenol F (BPF), an EDC that affects the thyroid, reproductive health, and immune cell function, is a common substitute for bisphenol A (BPA) and is used in manufacturing polycarbonates and consumer products. EDC exposure effects likely vary in the population, indicating gene x EDC interactions; however, genetic risk factors interacting with EDCs are unknown. In vivo toxicity studies performed in isogenic or genetically undefined outbred models may obscure or overemphasize exposure outcomes and do not address significant variability in population-level effects. These limitations can be avoided by studying the N/NIH Heterogeneous Stock (HS) rats, an outbred population derived from eight founder inbred strains readily amenable to genetic study. We hypothesize that BPF-induced metabolic disease has underlying genetic risk, which can be identified using HS rats and their founding inbred strains. We previously demonstrated that post-wean BPF exposure increases body growth and adiposity in male HS rats. We evaluated the metabolic impact of post-weaning BPF exposure in BUF/Mna rats, one of the HS-founding inbred strains that has genetic risks for thymic hyperplasia and focal segmental glomerulosclerosis. Weanling littermate pairs of male and female BUF rats were randomly exposed to either vehicle (0.1% EtOH) or 1.125 mg BPF/L in 0.1% EtOH for 10 weeks in drinking water. Metabolic measures, tissues, urine, and feces were taken. Males exposed to BPF did not differ from vehicle control. In females, BPF exposure did not change body composition or body weight gain; however, examination of two metabolic cage time points found that BPF females had decreased energy efficiency (weight gained/calorie absorbed) compared to vehicle control. There was an energy balance disruption in BPF females with increased 24 hr distance traveled and decreased resting metabolic rate compared to vehicle females. Also, BPF females had increased thymus and kidney mass compared to vehicle females. Our preliminary data indicate that post-wean BPF exposure affects immune, metabolic, and renal phenotypes in BUF rats in a sex-specific manner. These results suggest that BPF exacerbates inherent organ dysfunction in a genetically susceptible HS-founding inbred strain. This work supports BPF exposure as a metabolic disease risk factor and indicates that the HS rat will be a useful model for dissecting gene x BPF interactions on metabolic health. NIH T32 GM008629, NIH P30 ES005605, NIH R24 OD024617. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.