These authors contributed equally to this work

Exposure to bisphenol A (BPA) in utero has been shown to induce alterations in the prostate of 30 d-old Wistar rats. Herein, we examine both the time course of BPA action on the rat prostate and the effects of BPA on the male hypothalamic-pituitary-gonadal axis. This was achieved by exposing rats to BPA in utero, followed by immunohistochemistry and morphometric analysis of the prostatic tissue, evaluation of ER and ER mRNA expression in both the preoptic area (POA) and medial basal hypothalamus (MBH), and by determination of prolactin, LH and testosterone serum levels. At d 30 (peripubertal period), the prostatic periductal stroma of BPA-exposed rats demonstrated a significantly larger layer of fibroblasts than controls, whereas on d 120 (adulthood) no significant differences were observed. Moreover, BPA-exposed rats at d 15 exhibited an increase in stromal cellular proliferation in comparison to controls. Decreased expression of both androgen receptor in prostatic stromal cells and prostatic acid phosphatase in epithelial cells was observed only at d 30 in BPA-exposed males. BPA did not alter POA ER mRNA expression, whereas a 4-fold increase in POA ER mRNA expression was observed at both d 30 and d 120. No alterations were observed in either ER or ER expression in the MBH. BPA-exposed males exhibited increased prolactin levels only at d 30, while a transient increase in testosterone serum levels was observed at d 15. These results support the hypothesis that prenatal exposure to environmental doses of BPA induces both transient and permanent age-dependent alterations in the male reproductive axis at different levels.