Bisphenol A induces both transient and permanent histofunctional alterations of the hypothalamic-pituitary-gonadal axis in prenatally exposed male rats

RAMOS JG; VARAYOUD J; KASS L; RODRÍGUEZ HA; COSTABEL L; MUÑOZ-DE-TORO M; LUQUE EH

ENDOCRINOLOGY

Año: 2003 vol. 144 p. 3206 - 3215

0013-7227

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 therat prostate and the effects of BPA on the male hypothalamicpituitary-gonadal axis. This was achieved by exposing rats to BPA in utero, followed by immunohistochemistry and morphometric analysis of prostatic tissue, evaluation of estrogen receptor-alpha (ERa) and ERbmRNA expression in both the preoptic area (POA) and medial basal hypothalamus, and determination of PRL, LH, and testosterone serum levels. On d 30 (peripubertal period), the prostatic periductal stroma of BPA exposed rats demonstrated a significantly larger layer of fibroblasts than that of controls, whereas on d 120 (adulthood) no significant differences were observed. Moreover, BPA exposed rats on d 15 exhibited an increase in stromal cellularproliferation compared with controls. Decreased expression of both androgen receptor in prostatic stromal cells and prostatic acid phosphatase in epithelial cells was observed only ond 30 in BPA-exposed males. BPA did not alter POA ERmRNA expression, whereas a 4-fold increase in POA ERmRNA expression was observed on both d 30 and 120. No alterationswere observed in either ERor ERexpression in the medial basal hypothalamus. BPA-exposed males exhibited increased PRL levels only on d 30, whereas a transient increase in serum testosterone levels was observed on d 15. These results supportthe hypothesis that prenatal exposure to environmental doses of BPA induces both transient and permanent agedependent alterations in the male reproductive axis at different levels.