Exposure to bisphenol A disrupts meiotic progression during spermatogenesis in adult rats through estrogen-like activity.

C Liu,M Zhong,Z Yu,Y Zhang,S Xu,W Duan,C Chen,X Luo,Z Zhou,R Li,H Pi,L Zhang,M He,H Wu,Y Lu

doi:10.1038/cddis.2013.203

Abstract

The effect of bisphenol A (BPA) on the reproductive system is highly debated but has been associated with meiotic abnormalities. However, evidence is lacking with regard to the mechanisms involved. In order to explore the underlying mechanisms of BPA-induced meiotic abnormalities in adult male rats, we exposed 9-week-old male Wistar rats to BPA by gavage at 0, 2, 20 or 200 μg/kg body weight (bw)/day for 60 consecutive days. 17β-Estradiol (E2) was administered at 10 μg/kg bw/day as the estrogenic positive control. Treatments with 200 μg/kg bw/day of BPA and E2 significantly decreased sperm counts and inhibited spermiation, characterized by an increase in stage VII and decrease in stage VIII in the seminiferous epithelium. This was concomitant with a disruption in the progression of meiosis I and the persistence of meiotic DNA strand breaks in pachytene spermatocytes,and the ataxia–telangiectasia-mutated and checkpoint kinase 2 signal pathway was also activated; Eventually, germ cell apoptosis was triggered as evaluated by terminal dUTP nick-end labeling assay and western blot for caspase 3. Using the estrogen receptor (ER) antagonist ICI 182780, we determined that ER signaling mediated BPA-induced meiotic disruption and reproductive impairment. Our results suggest that ER signaling-mediated meiotic disruption may be a major contributor to the molecular events leading to BPA-related male reproductive disorders. These rodent data support the growing association between BPA exposure and the rapid increase in the incidence of male reproductive disorders.

Highlights

In 480% of sterile women, lower antral follicle counts and a smaller ovarian volume have been associated with higher levels of Bisphenol A (BPA) in urine.[7]
After 60 consecutive days of exposure, treatment with 200 mg/kg/d of BPA and 17b-estradiol (E2) significantly reduced the epididymal sperm counts; the effect of BPA was reversed by ICI pretreatment (Figure 1a)
A histological examination showed fewer sperm in the cauda epididymal ducts following BPA treatment at 200 mg/kg/d compared with the control group, which was abolished by ICI pretreatment (Figures 1e–l)

Summary

Introduction

In 480% of sterile women, lower antral follicle counts and a smaller ovarian volume have been associated with higher levels of BPA in urine.[7]. Growing evidences show that BPA has the capacity to disrupt meiotic events and subsequently impair reproductive function; BPA exposure has been reported to impair chromosome synapsis and homologous chromosome segregation,[14] induce synaptic defects, such as end-to-end chromosome associations and asynapsis,[9] and delay meiotic progression.[15]. Recent studies have demonstrated that BPA exposure inhibits meiotic double-strand break repair,[14] induces meiotic aneuploidy,[16] and eventually causes meiotic arrest[17] or chromosomal abnormalities.[18] most of these studies were performed in females, and evidence is lacking with regard to the effect of BPA exposure on meiosis in males. We performed an in vivo study to evaluate the possible effects of BPA on reproductive function and the

Methods

Results

Conclusion