BACKGROUND: Bisphenol 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.
METHODS: Adult 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.
RESULTS: The 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.