PM2.5 induces male reproductive toxicity via mitochondrial dysfunction, DNA damage and RIPK1 mediated apoptotic signaling pathway.

Recent years, air pollution has been a serious problem, and PM2.5 is the main air particulate pollutant. Studies have investigated that PM2.5 is a risky factor to the deterioration of semen quality in males. But, the related mechanism is still unclear. To explore the effect of PM2.5, Sprague Dawley (SD) rats were exposed to PM2.5 (0, 1.8, 5.4 and 16.2mg/kg.bw.) through intratracheal instillation. The exposure was performed once every 3days and continued for 30days. In vitro, GC-2spd cells were treated using 0, 50, 100, 200μg/mL PM2.5 for 24h. The data showed that sperm relative motility rates and density were remarkably decreased, while sperm malformation rates were significantly increased with exposure to the PM2.5. The expression of Fas/FasL/RIPK1/FADD/Caspase-8/Caspase-3 and the level of 8-OHdG expression in testes were significantly increased after exposure to PM2.5. Additionally, in vitro the results showed that PM2.5 inhibited cell viability, increased the release of lactate dehydrogenase (LDH) by increasing reactive oxygen species (ROS) level. And ROS induced-DNA damage led to cell cycle arrest at G0/G1 phases and proliferation inhibition. Similar to the vivo study, the expressions of Fas/FasL/RIPK1/FADD/Caspase-8/Caspase-3 in GC-2spd cells were significantly increased after exposure to PM2.5 for 24-h. In addition, PM2.5 decreased the levels of ATP by impairing mitochondria structures, which led to energy metabolism obstruction resulted in the decrease of sperm motility. The above three aspects together resulted in the decrease in sperm quantity and quality.