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

Endocrinology. 2003 Jul;144(7):3206-15. doi: 10.1210/en.2002-0198.


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 prostatic tissue, evaluation of estrogen receptor-alpha (ERalpha) and ERbeta mRNA 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 cellular proliferation compared with controls. Decreased expression of both androgen receptor in prostatic stromal cells and prostatic acid phosphatase in epithelial cells was observed only on d 30 in BPA-exposed males. BPA did not alter POA ERalpha mRNA expression, whereas a 4-fold increase in POA ERbeta mRNA expression was observed on both d 30 and 120. No alterations were observed in either ERalpha or ERbeta expression 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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds
  • Cell Division / physiology
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Estrogens, Non-Steroidal / pharmacology*
  • Female
  • Hypothalamo-Hypophyseal System / drug effects*
  • Hypothalamo-Hypophyseal System / embryology
  • Luteinizing Hormone / blood
  • Male
  • Phenols / pharmacology*
  • Phenotype
  • Pituitary-Adrenal System / drug effects*
  • Pituitary-Adrenal System / embryology
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Preoptic Area / embryology
  • Preoptic Area / physiology
  • Prolactin / blood
  • Prostate / cytology
  • Prostate / drug effects*
  • Prostate / embryology
  • RNA, Messenger / analysis
  • Rats
  • Rats, Wistar
  • Receptors, Estrogen / genetics
  • Stromal Cells / cytology
  • Testosterone / blood


  • Benzhydryl Compounds
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Estrogens, Non-Steroidal
  • Phenols
  • RNA, Messenger
  • Receptors, Estrogen
  • Testosterone
  • Prolactin
  • Luteinizing Hormone
  • bisphenol A