Neonatal genistein or bisphenol-A exposure alters sexual differentiation of the AVPV

There is growing concern that naturally occurring and chemically manufactured endocrine-active compounds (EACs) may disrupt hormone-dependent events during central nervous system development. We examined whether postnatal exposure to the phytoestrogen genistein (GEN) or the plastics component bisphenol-A (BIS) affected sexual differentiation of the anteroventral periventricular nucleus of the hypothalamus (AVPV) in rats. The AVPV is sexually differentiated in rodents. The female AVPV is larger than the male AVPV and contains a higher number of cells expressing tyrosine hydroxylase (TH). Sexual differentiation of the AVPV results from exposure of the male nervous system to estrogen aromatized from testicular testosterone secreted in the first few days after birth. Thus, we hypothesized that exposure to EACs during this critical period could alter the sexually dimorphic expression of TH and the overall expression of estrogen receptor alpha (ERα) in the AVPV. Animals were given 4 subcutaneous injections of sesame oil (control), 50 μg 17β-estradiol (E₂), 250 μg GEN, or 250 μg BIS at 12-h intervals over postnatal days (PND) 1 and 2 and sacrificed on PND 19. E ₂ treatment masculinized TH immunoreactivity (TH-ir) in the female AVPV while exposure to GEN or BIS demasculinized TH-ir in the male AVPV. In addition, we identified a population of neurons co-expressing TH and ERα located primarily in the medial region of the AVPV. Normally, females have nearly three times as many double-labeled cells as males, but their numbers were defeminized by E₂, GEN or BIS treatment. These results suggest that acute exposure to EACs during a critical developmental period alters AVPV development.