Sex-specific Esr2 mRNA expression in the rat hypothalamus and amygdala is altered by neonatal bisphenol A exposure

Abstract

Perinatal life is a critical window for sexually dimorphic brain organization, and profoundly influenced by steroid hormones. Exposure to endocrine-disrupting compounds may disrupt this process, resulting in compromised reproductive physiology and behavior. To test the hypothesis that neonatal bisphenol A (BPA) exposure can alter sex-specific postnatalEsr2(Erβ) expression in brain regions fundamental to sociosexual behavior, we mappedEsr2mRNA levels in the principal nucleus of the bed nucleus of the stria terminalis (BNSTp), paraventricular nucleus (PVN), anterior portion of the medial amygdaloid nucleus (MeA), super optic nucleus, suprachiasmatic nucleus, and lateral habenula across postnatal days (PNDs) 0–19. Next, rat pups of both sexes were subcutaneously injected with 10 μg estradiol benzoate (EB), 50 μg/kg BPA (LBPA), or 50 mg/kg BPA (HBPA) over the first 3 days of life andEsr2levels were quantified in each region of interest (ROI) on PNDs 4 and 10. EB exposure decreasedEsr2signal in most female ROIs and in the male PVN. In the BNSTp,Esr2expression decreased in LBPA males and HBPA females on PND 10, thereby reversing the sex difference in expression. In the PVN,Esr2mRNA levels were elevated in LBPA females, also resulting in a reversal of sexually dimorphic expression. In the MeA, BPA decreasedEsr2expression on PND 4. Collectively, these data demonstrate that region- and sex-specificEsr2expression is vulnerable to neonatal BPA exposure in regions of the developing brain critical to sociosexual behavior in rat.