Mutual promotion of apoptosis and autophagy in prepubertal rat testes induced by joint exposure of bisphenol A and nonylphenol

Abstract

BPA and NP are both typical endocrine disruptors, the exposed populations are widespread, and the health risks mustn't be ignored. However, the interactions between them on spermatogenesis are rarely mentioned. And the underlying mechanism is unclear yet. In the present study, prepubertal SD rats were exposed to different low doses of BPA and NP separately or jointly for 4 weeks. The results indicate that the joint exposure induced excessive apoptosis and autophagy in the testes, as proved by a series of characteristics such as chromatin condensation and autophagosomes formation. Besides, endocrine disorders and oxidative stress were also caused by the exposure. Apoptosis was mediated by the mitochondrial apoptosis pathway, since the Bax and Caspase-3 gene expressions significantly increased with a prominent decrease of Bcl-2. While autophagy was caused by the inhibition of the Akt/mTOR pathway, as the expressions of the downstream genes Beclin-1, Atg5, Atg12 and the split of LC3 protein increased altogether. Worse yet, autophagy and apoptosis might reinforce each other and make the situation more severe in the joint group. What's more, remarkable histopathological changes such as spermatogenic epithelium atrophy, germ cell loss, and various ultrastructural modifications were strongly related to the apoptosis and autophagy. In aggregate, this study shows the enormous risk on male reproductive system brought by the interactions between BPA and NP. The findings provide a broader vision to understand the roles of apoptosis and autophagy induced by the joint exposure in the aggravation of spermatogenesis impairment, which could be a reference for the situation of complex EDCs exposure-induced male reproductive toxicity, and possibly inspire us to find new ideas for preventive and therapeutic treatments.