Cytotoxicity and DNA Damage Caused from Diazinon Exposure by Inhibiting the PI3K-AKT Pathway in Porcine Ovarian Granulosa Cells

Organophosphorus insecticide diazinon (DZN) is diffusely used in agriculture, home gardening and crop peats. Much work so far has focused on the link between DZN exposure and the occurrence of neurological diseases, while, it is little-known that reproductive toxicological assessment on DZN exposure. This research aimed to investigate the underlying mechanisms of toxic hazard for DZN exposure on the cultured porcine ovarian granulosa cells. We analyzed the oxidative stress, energy metabolism, DNA damage, apoptosis and autophagy by using high-throughput RNA-seq, immunofluorescence, western blotting and real-time PCR. The combined data demonstrated that DZN exposure could cause excessive ROS and DNA damage, which induced apoptosis and autophagy by inhibiting the PI3K-AKT pathway. The down-regulated CYP19A1 protein and granulosa cells death increase the risk for developing the premature ovarian failure and the follicular atresia. In conclusion, DZN exposure has obvious reproductive toxicity by induction of granulosa cell death through pathways connected to DNA damage and oxidative stress by inhibiting the PI3K-AKT pathway.