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

Abstract

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 induces oxidative stress‐mediated impairment of testosterone synthesis by inhibiting the Nrf2/HO‐1 signaling pathway

“…Our early research indicated that BPS can cause a reduction in SOD and GSH‐Px activities as well as glutathione levels in the testis of mice, which is accompanied by an increase in the end product of lipid peroxide malondialdehyde. [ 20 ] This observation suggests the induction of oxidative stress by BPS in mouse testicular tissue. Here, we further investigated whether BPS could induce oxidative stress in testicular tissue by inhibiting the Nrf2/HO‐1 signaling pathway.…”

“…The dose chosen was based on our previous study. [ 20 ] The mice from each group were killed on the 29th day after treatment. The blood was collected and centrifuged at 1000 g for 10 min; then, the serum was stored at −20°C until enzyme‐linked immunosorbent assay (ELISA).…”

“…Accordingly, there may be a relationship between oxidative stress occurring and testosterone synthesis impairment in Leydig cells. [ 19 ] BPS can also induce oxidative stress in the testis of mice, [ 20 ] but whether BPS disrupts steroid hormone synthesis by directly changing the levels of enzymes in the hormone biosynthesis pathway through oxidative stress is still unclear.…”

Di(2‐ethylhexyl) phthalate and microplastics cause necroptosis and apoptosis in hepatocytes of mice by inducing oxidative stress

“…The intrinsic pathway proapoptotic proteins Bcl‐2‐associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (Caspase3) lie upstream of mitochondrial oxidative stress‐inducing activity, and also play a vital role in the generation of oxidative stress in adult mouse organs 21 . Bisphenol S exposure can cause oxidative stress and apoptosis in spermatogenic cells 22 . Oxidative stress‐induced cardiomyocyte apoptosis through abnormalities in the Akt/p53 signaling pathway 23 .…”

“…21 Bisphenol S exposure can cause oxidative stress and apoptosis in spermatogenic cells. 22 Oxidative stress-induced cardiomyocyte apoptosis through abnormalities in the Akt/p53 signaling pathway. 23 The research by Ren et al has shown that oxidative stress can induce apoptosis by destroying mitochondrial structure, and the onset of type 2 diabetes is related to its damage to the normal function of islet β cells.…”