Sex and Dose-Dependent Effects of Developmental Exposure to Bisphenol A on Anxiety and Spatial Learning in Deer Mice (Peromyscus maniculatus bairdii) Offspring

摘要

Bisphenol A (BPA) is a widely produced, endocrine disrupting compound that is pervasive in the environment. Data suggest that developmental exposure to BPA during sexual differentiation of the brain leads to later behavioral consequences in offspring. Outbred deer mice (Peromyscus maniculatus bairdii) are an excellent animal model for such studies as they exhibit well-defined sex- and steroid-dependent behaviors. Here, dams during gestation and lactation were fed a phytoestrogen-free control diet, the same diet supplemented with either ethinyl estradiol (0.1 parts per billion), or one of three doses of BPA (50 mg, 5 mg, 50 μg/kg feed weight). After weaning, pups were maintained on control diet until they reached sexually maturity and then assessed for both spatial learning capabilities and anxiety-like and exploratory behaviors. Relative to controls, males exposed to the two upper but not the lowest dose of BPA demonstrated similar impairments in spatial learning, increased anxiety and reduced exploratory behaviors as ethinyl estradiol-exposed males, while females exposed to ethinyl estradiol, but not to BPA, exhibited masculinized spatial abilities. We also determined whether dams maintained chronically on the upper dose of BPA contained environmentally relevant concentrations of BPA in their blood. While serum concentrations of unconjugated BPA in controls were below the minimum level of detection, those from dams on the BPA diet were comparable (5.48 ± 2.07ng/ml) to concentrations observed that have been observed in humans. Together, these studies demonstrate that developmental exposure to environmentally relevant concentrations of BPA can disrupt adult behaviors in a dose- and sex-dependent manner.