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

Abstract

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 little is known on the reproductive toxicological assessment on DZN exposure. This research aimed to investigate the underlying mechanisms of toxic hazards for DZN exposure on 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 cell deaths increase the risk for developing premature ovarian failure and 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.

Small extracellular vesicles derived from embryonic stem cells restore ovarian function of premature ovarian failure through PI3K/AKT signaling pathway

“…In addition, the PI3K/AKT pathway participates in oocyte growth, primordial follicular development, and granulosa cell proliferation and apoptosis. In previous studies, cytotoxic drugs were found to lead to apoptosis of granulosa cells and increase the risk of developing POF by significantly inhibiting the PI3K/AKT signaling pathway [24]. However, whether PI3K/AKT signaling is involved in ESCs-sEVs treatment for POF remained to be further explored.…”

Roles of Resveratrol in Improving the Quality of Postovulatory Aging Oocytes In Vitro

“…Oocytes were processed by using the oxidation-sensitive fluorescent probe at 37 °C for 30 min according to the Reactive Oxygen Species Assay Kit (Beyotime Institute of Biotechnology, Shanghai, China). To detect the fluorescent intensity of ROS, the confocal system was used with the same scanning settings [27].…”

Berberine Supplement and Resistance Training May Ameliorate Diazinon Induced Neural Toxicity in Rat Hippocampus Via the Activation of the TrkB and ERK Signaling Pathway

“…5,35,36 In other tissues, Wang and colleagues showed that cytotoxicity and DNA damage were caused by diazinon exposure through inhibiting the PI3K-AKT pathway in porcine ovarian granulosa cells. 37 Therefore, it seems that in the brain tissue, diazinon with increasing oxidative stress affected PI3K, CKD1, ERK and TRKB and reduction in these factors increases susceptibility of the brain to degenerative disease. Using herbal supplements can reduce the destructive effects of the ROS.…”