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  2. Co-exposure of microcystin and nitrite enhanced spermatogenic disorders: The role of mtROS-mediated pyroptosis and apoptosis

Co-exposure of microcystin and nitrite enhanced spermatogenic disorders: The role of mtROS-mediated pyroptosis and apoptosis

  • Environ Int. 2024 May 22:188:108771. doi: 10.1016/j.envint.2024.108771.
Haohao Liu 1 Xingde Du 2 Zongxin Zhang 2 Kangfeng Ge 2 Xinghai Chen 3 Michael D Losiewicz 3 Hongxiang Guo 4 Huizhen Zhang 5
Affiliations

Affiliations

  • 1 College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China; Department of Public Health, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450001, Henan, China.
  • 2 College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China.
  • 3 Department of Chemistry and Biochemistry, St Mary's University, San Antonio, TX, USA.
  • 4 College of Life Sciences, Henan Agricultural University, Zhengzhou, 450002 Henan, China. Electronic address: guohongxiang06@126.com.
  • 5 College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China. Electronic address: huizhen18@126.com.
Abstract

Microcystins (MCs) and nitrites are coexisted in the environment and have reproductive toxicity. The combined toxic effect and mechanism of MCs and nitrite on spermatogenesis remain largely unclear. In the present study, co-exposure to microcystin-leucine arginine (MC-LR) and sodium nitrite (NaNO2) aggravated testicular damage of Balb/c mice and mitochondrial impairment of spermatogonia, Sertoli cells, and sperm. Furthermore, MC-LR and NaNO2 reduced sperm density with a synergistic effect. In addition, MC-LR and NaNO2 synergistically induced oxidative stress in the reproductive system by decreasing superoxide dismutase (SOD) activity and glutathione (GSH) levels and increasing levels of mitochondrial Reactive Oxygen Species (mtROS) and Reactive Oxygen Species (ROS). More importantly, mitoquidone mesylate (MitoQ), an inhibitor of mtROS, blocked MC-LR and NaNO2-induced spermatogonia and Sertoli cell Apoptosis by inhibiting high expression of Bax, Fadd, Caspase-8, and cleaved-Caspase-3. On the other hand, MitoQ suppressed Pyroptosis of Sertoli cells by inhibiting the expression of NLRP3, N-GSDMD, and cleaved-Caspase-1. Additionally, MitoQ alleviated co-exposure-induced sperm density reduction and organ index disorders in F1 generation mice. Together, co-exposure of MC-LR and NaNO2 can enhance spermatogenic disorders by mitochondrial oxidative impairment-mediated germ cell death. This study emphasizes the potential risks of MC-LR and NaNO2 on reproduction in realistic environments and highlights new insights into the cause and treatment of spermatogenic disorders.

Keywords

Microcystins; Mitochondrial oxidative impairment; Nitrite; Reproductive toxicity; Spermatogenic disorders.

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