Nickel induces blood-testis barrier damage through ROS-mediated p38 MAPK pathways in mice
Yuxin Zeng,
Qing Yang,
Yujuan Ouyang,
Yanbin Lou,
Hengmin Cui,
Huidan Deng,
Yanqiu Zhu,
Yi Geng,
Ping Ouyang,
Lian Chen,
Zhicai Zuo,
Jing Fang,
Hongrui Guo
Affiliations
Yuxin Zeng
College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, PR China
Qing Yang
College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, PR China
Yujuan Ouyang
College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, PR China
Yanbin Lou
College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, PR China
Hengmin Cui
College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, PR China; Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu, 611130, PR China
Huidan Deng
College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, PR China; Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu, 611130, PR China
Yanqiu Zhu
College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, PR China
Yi Geng
College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, PR China
Ping Ouyang
College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, PR China
Lian Chen
College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, PR China; Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu, 611130, PR China
Zhicai Zuo
College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, PR China; Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu, 611130, PR China; Corresponding author. College of Veterinary Medicine Sichuan Agricultural University Chengdu, Sichuan, 625014, China.
Jing Fang
College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, PR China; Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu, 611130, PR China; Corresponding author. College of Veterinary Medicine Sichuan Agricultural University Chengdu, Sichuan, 625014, China.
Hongrui Guo
College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, PR China; Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu, 611130, PR China; Corresponding author. College of Veterinary Medicine Sichuan Agricultural University Chengdu, Sichuan, 625014, China.
Nickel (Ni) is an essential common environmental contaminant, it is hazardous to male reproduction, but the precise mechanisms are still unknown. Blood-testis barrier (BTB), an important testicular structure consisting of connections between sertoli cells, is the target of reproductive toxicity caused by many environmental toxins. In this study, ultrastructure observation and BTB integrity assay results indicated that NiCl2 induced BTB damage. Meanwhile, BTB-related proteins including the tight junction (TJ), adhesion junction (AJ) and the gap junction (GJ) protein expression in mouse testes as well as in sertoli cells (TM4) were significantly decreased after NiCl2 treatment. Next, the antioxidant N-acetylcysteine (NAC) was co-treated with NiCl2 to study the function of oxidative stress in NiCl2-mediated BTB deterioration. The results showed that NAC attenuated testicular histopathological damage, and the expression of BTB-related proteins were markedly reversed by NAC co-treatment in vitro and vivo. Otherwise, NiCl2 activated the p38 MAPK signaling pathway. And, NAC co-treatment could significantly inhibit p38 activation induced by NiCl2 in TM4 cells. Furthermore, in order to confirm the role of the p38 MAPK signaling pathway in NiCl2-induced BTB impairment, a p38 inhibitor (SB203580) was co-treated with NiCl2 in TM4 cells, and p38 MAPK signaling inhibition significantly restored BTB damage induced by NiCl2 in TM4 cells. These results suggest that NiCl2 treatment destroys the BTB, in which the oxidative stress-mediated p38 MAPK signaling pathway plays a vital role.
