Cross-talk between autophagy and apoptosis regulates testicular injury/recovery induced by cadmium via PI3K with mTOR-independent pathway

Autophagy and apoptosis are two major modes of cell death. A balanced interplay between both is vital for phagocytic clearance of apoptotic testicular cells. Here, generating a SD rats model-treated with cadmium (Cd) to mimic environmental exposure on human, we show that autophagy and apoptosis present synchronous change trends in Cd-induced testicular injury/self-recovery. Further, the cross-talk of autophagy and apoptosis is investigated in four testicular cell lines (GC-1/GC-2/TM3/TM4 cells) respectively. Results reveal that Cd-exposure for five consecutive weeks induces reproductive toxicity in male rats. After one cycle of spermatogenesis within 8 weeks without Cd, toxic effects are ameliorated significantly. In vitro, we find that PI3K inhibitor 3-MA regulates apoptosis by inhibiting autophagy with mTOR-independent pathway in Cd-treated testicular cells. Conclusively, cross-talk between autophagy and apoptosis regulates testicular injury/recovery induced by Cd via PI3K with mTOR-independent pathway.