Oxidative stress‐mediated apoptosis is involved in bisphenol S‐induced reproductive toxicity in male C57BL/6 mice

The reproductive toxicity of bisphenol S (BPS) in male mammals and its possible mechanism are not clear. We investigated the effects and possible mechanism of action of BPS on adult male C57BL/6 mice. We found that exposure to 200‐mg/kg BPS resulted in a significant decrease in the sperm count in the caput/corpus and cauda epididymis, significantly decreased sperm motility, and significantly increased the sperm deformity. Histological evaluation revealed that BPS exposure caused a decrease of spermatozoa in the lumen of seminiferous tubules and a reduction in the proportion of Stage VII or VIII seminiferous tubules in the BPS‐treated groups. Furthermore, ultrastructure analysis revealed BPS‐induced mitochondrial damage and apoptosis in spermatogenic cells. Moreover, BPS exposure‐induced oxidative stress in testicular tissues. Further, dUTP‐biotin nick end labeling (TUNEL) assay showed that BPS induced the apoptosis of spermatogenic cells in a dose‐dependent manner. BPS also significantly upregulated cleaved caspase‐8, cleaved caspase‐9, cleaved caspase‐3, Fas, and FasL and significantly downregulated the Bcl‐2/Bax ratio. These results suggest that BPS‐induced oxidative stress in the testis and spermatogenic cell apoptosis potentially impairs spermatogenesis and sperm function, which may be the mechanism of the reproductive toxicity of BPS. The Fas/FasL and mitochondrial signal pathways may be involved in BPS‐induced oxidative stress‐related apoptosis. These results suggest that BPS‐induced oxidative stress in the testis and spermatogenic cell apoptosis potentially impairs spermatogenesis and sperm function, which may be the mechanism of the reproductive toxicity of BPS. The Fas/FasL and mitochondrial signal pathways may be involved in BPS‐induced oxidative stress‐related apoptosis. Bisphenol S (BPS) decreased sperm count and increased sperm deformity rate significantly in the epididymis. BPS resulted in decrease of spermatozoa in the lumen of seminiferous tubules and a reduction in the proportion of Stage VII or VIII seminiferous tubules. The Fas/FasL and mitochondrial signal pathways may be involved in BPS‐induced oxidative stress‐related apoptosis in the testis.