Bisphenol A exposure decreases sperm production and male fertility through inhibition PCBP2 expression

Abstract

Growing evidence suggests that exposure of Bisphenol A (BPA), an endocrine disruptor that commonly presence in the environment, can impair reproduction. However, con icting results have been reported and the underling mechanism have not been fully understood. In this study, 3 weeks old male mice were exposed to 50mg/kg/d BPA or equivalent corn oil for 28 days. Their testis and epididymis were then collected for morphology examination by HE stains. The number of sperm were counted, and the morphology was analyzed by PNA and pap staining. Fertilization capacity and successful rate was analyzed after mating with wide type females. Spermatid DNA damage and apoptosis were evaluated by DFI, γH2AX stain and TUNEL assay. RNA-seq analysis was conducted to identify differentially expressed genes in testicular tissue of mice exposed to BPA. RNA interference was used to verify the regulatory mechanism of BPA exposure on gene expression in GC-2 cells. Our data showed that total number of sperm was decreased and the morphology was impaired in BPA-exposed mice. In addition, the serum testosterone level and fertilization e ciency were also reduced. Mechanism studies showed that BPA could suppress the expression of PCBP2, a key regulatory gene in spermatid development, by activating the EZH2/H3K27me3. In conclusion, we found that BPA exposure can impair spermatid development via affecting key gene expression that at least partially due to epigenetic modi cation.