Chronic exposure of BPA impairs male germ cell proliferation and induces lower sperm quality in male mice

Abstract

BackgroundBisphenol A (BPA) is a well-known endocrine disruptor that affects male fertility. However, the main biological events through which BPA affects spermatogenesis remain to be identified. MethodsAdult male mice were treated by feeding with drinking water containing BPA (0.2 μg/ml, 20 μg/ml, 200 μg/ml, respectively) for two months. Testes were collected for protein extraction or for immunohistochemical analysis. Epididymal spermatozoa were collected for sperm quality evaluation and male fertility assay by in vitro fertility (IVF). Serums were collected for detection of testosterone levels. Proteins associated with germ cell proliferation, meiosis, blood-testis barrier, and steroidogenesis production were examined in BPA-treated and control mice testes. CCK8 assay was used to detect the effect of BPA on the proliferation of GC-1 and GC-2 cells. ResultsThe BPA-treated mice were characterized by decreased sperm quality, serum testosterone levels and, sub-fertile phenotype characterizing with low pregnancy rates and reduced fertilization efficiency. In lower BPA (0.2 μg/ml) treatment, PCNA and PLZF were down-expressed that indicated impaired germ cell proliferation. SYCP3 was down-expressed in BPA-treated mice, but expressions of other proteins associated with meiosis and blood-testis barrier were not significantly altered. CYP11A1 and HSD3B1 were down-expressed in BPA-treated mice that demonstrated reduced steroidogenesis activity. BPA has a concentration-dependent inhibition effect on the proliferation of GC-1 and GC-2 cells. Conclusively, low doses BPA exposure reduced mice sperm quality mainly by impairing germ cell proliferation, leading to reduced male fertility. The study would provide relevant information for investigation on molecular mechanisms and protective strategy on male production.