| Endocrine disrupting compounds (EDCs) are exogenous chemicals that interfere with the endocrine system and hormone action. EDC action, particularly on sex hormones, indicates that they may participate in the aberrant organization or activation of sex differences within the brain. Bisphenol A (BPA) is one such EDC and has previously reported to affect sex-specific neuroendocrine physiology, estrogen signaling, and behavior. The mechanisms underlying these brain and behavior outcomes are largely unknown and defining them would allow for determination of their human relevance and potential contribution to human disease, such as neuropsychiatric disorders. This work investigates the potential for BPA to act on neuroendocrine physiology and behavior in three ways: (1) neonatal alteration of estrogen receptor expression by prenatal exposure to BPA, (2) juvenile and adult alteration of estrogen receptor expression by subchronic exposure to BPA, and (3) juvenile and adult alteration of anxiety and activity behavior by perinatal exposure to BPA. Sprague Dawley rats were gavaged on gestational days 6--21 for neonatal and perinatal exposures, and further dosed until postnatal day 90 for subchronic exposures, with vehicle, 2.5 to 2700 mug/kg bw/day BPA, or 0.5, 5, or 10 mug/kg bw/day ethinyl estradiol. Estrogen receptor expression in the hypothalamus and amygdala was investigated using in situ hybridization, while behavior was evaluated using a battery of behavioral tests including the elevated plus maze, open field and zero maze. Significant effects of BPA were observed in the neonate on estrogen receptor expression in the mediobasal hypothalamus and amygdala in both sexes. In the juvenile and adult, effects of BPA on estrogen receptor expression were primarily seen in subregions of the preoptic area of female rats. Finally, there were no consistent effects of BPA on anxiety or activity behaviors, however study limitations limit the ability make resolute conclusions on BPA's potential to alter affective behaviors. These results indicate that estrogen receptor expression in the neonatal, juvenile and adult brain can be altered by BPA and may be one mechanism by which BPA can alter brain and behavior outcomes. |
