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

  • Cell Death Dis. 2020 Jan 22;11(1):46. doi: 10.1038/s41419-020-2246-1.
Mei Wang  1  2  3 ,  Xiao-Fei Wang  1 ,  Ya-Min Li  1 ,  Na Chen  1 ,  Yan Fan  1 ,  Wen-Kai Huang  4 ,  Shi-Fu Hu  1 ,  Meng Rao  5 ,  Yuan-Zhen Zhang  6 ,  Ping Su  7  8
Affiliations
  • 1. Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, P.R. China.
  • 2. Department of Obstetrics and Gynecology/Reproductive Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan, 430071, Hubei, P.R. China.
  • 3. Harvard Reproductive Endocrine Science Center and Reproductive Endocrine Unit of the Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
  • 4. Reproductive Medicine Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, P.R. China.
  • 5. Department of Reproduction and Genetics, The First Affiliated Hospital of Kunming Medical University, Kunming, 650000, Yunnan, P.R. China.
  • 6. Department of Obstetrics and Gynecology/Reproductive Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan, 430071, Hubei, P.R. China. [email protected].
  • 7. Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, P.R. China. [email protected].
  • 8. Reproductive Medicine Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, P.R. China. [email protected].
PMID: 31969557 DOI: 10.1038/s41419-020-2246-1
Abstract

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.

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