Bisphenol A Induces Both Transient and Permanent Histofunctional Alterations of the Hypothalamic-Pituitary-Gonadal Axis in Prenatally Exposed Male Rats

Abstract

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.

Perinatal exposure to low-dose bisphenol A affects the neuroendocrine stress response in rats

“…Nonetheless, to exclude the possibility that the detected BPA effects on HPA axis reflect alterations in gonadal steroids of the exposed animals, we have previously (Poimenova et al 2010) determined the circulating levels of progesterone and testosterone in mid-pubertal BPA-exposed rats treated under the same protocol. No differences were found between BPA-exposed and control animals, in compliance with previous studies (Ramos et al 2003, Muñoz-de-Toro et al 2005. In addition, in this study, monitoring of the estrous cycle also did not reveal differences between control and BPA-treated females that could possibly influence stress responses.…”

NTP‐CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A

“…Ramos et al (2003), supported by the Argentine Ministry of Health, Argentine National Agency for the Promotion of Science and Technology, and the National University of Litoral, examined the effects of bisphenol A exposure on the prostate and the hypothalamic-pituitarygonadal axis in Wistar rats. Rats were housed in stainless steel cages and 7-9/group were administered DMSO vehicle or bisphenol A at 0.025 or 0.250 mg/kg bw/day by s.c. pump on GD 8-23 (GD 1 5 day of vaginal sperm).…”

The estrogen receptor α Σ3 mRNA splicing variant is differentially regulated by estrogen and progesterone in the rat uterus

“…Reverse transcription and PCR amplification were performed following the technique previously described by Ramos et al (2003) with minor modifications. Total RNA was isolated from frozen uterine tissue using Trizol reagent (Life Technologies).…”

“…All linear correlation coefficients were greater than 0·97. Based on these results, and in accordance with our previously published protocols (Ramos et al 2003, Kass et al 2004, we have chosen 30 and 28 cycles for ER and GAPDH respectively, using separate reactions for each target gene. Representative ethidium bromide-stained images of ER and GADPH mRNA by RT-PCR analysis are shown in Fig.…”