Chlorpyrifos inhibits sperm maturation and induces a decrease in mouse male fertility

Pesticides, especially organophosphorus pesticides such as chlorpyrifos (CPF), play an important role in modern agriculture. Studies have shown that pesticide residues are an important cause of male reproductive injury in mammal. The aim of this study was to evaluate the reproductive damage caused by CPF in male mice and investigate the underlying mechanisms. In vivo, C57BL/6 mice (6–8 weeks old) were treated with CPF for 14, 70, and 80 days by intraperitoneal injection, intragastric administration, and dietary supplementation, respectively. Then, sperm from the cauda epididymidis was cultured in vitro to confirm the deleterious effects of CPF. The in vivo results indicated that, after treatment with CPF by dietary supplementation and intraperitoneal injection, the expression of reproduction-related genes in the mouse testes was altered, although the mice were fertile and the testes presented no morphological abnormalities. Notably, mating experiments revealed that the fertility of male mice was decreased following CPF administration by gavage. Sperm motility within the cauda epididymidis declined significantly after CPF treatment, which was accompanied by a decrease in sperm density, upregulation of relative reactive oxygen species (ROS) levels, and downregulation of glutathione reductase activity. In vitro incubation experiments showed that sperm rapidly lost their capacity for linear movement; the relative ROS levels also increased significantly, while the mitochondrial membrane potential (MMP) showed a significant decrease. However, the integrity of the plasma membrane was not affected by CPF administration. The above data indicated that exposure to CPF reduces sperm motility by disrupting mitochondrial function and increasing the level of oxidative stress during sperm maturation, thereby reducing the fecundity of male mice.