Diazinon induces testicular dysfunction and testicular cell damage through increased reactive oxygen species...

Diazinon (DZN) is an organophosphorus compound used as a pesticide and is an environmentally hazardous substance to which the human body is commonly exposed. In this study, we evaluated the toxicity of DZN to the male reproductive in mice. For in vivo experiments, mice were intraperitoneally injected with 30 mg/kg DZN for 35 days. Microscopic analysis revealed that the diameter of the spermatogonia in the testes decreased, and the number of differentiating germ cells decreased. Sperm motility in mice injected with DZN was reduced, and slow motility was observed. The rate of neck deformation in the sperm increased in DZN-treated mice. The number of germ and Sertoli cells decreased, and the levels of serum testosterone and steroidogenesis markers also decreased in DZN-treated mice. In addition, DZN-induced oxidative stress in the testes. For in vitro experiments, DZN was toxic to GC-1 spermatogonia and TM4 and TM3 cells derived from mouse testes. DZN generated reactive oxygen species (ROS) and induced mitochondrial dysfunction, suggesting a molecular mechanism underlying ROS-induced cell death. DZN upregulated BAD, cleaved-caspase 3, and phospho-p53 at the cellular level. We also found that this toxicity could be mitigated by N-acetyl-l-cysteine, an ROS inhibitor.