Toxic effects and possible mechanisms following malathion exposure in porcine granulosa cells.

Malathion is a wide spectrum organophosphorothionate insecticide that is frequently found in drinking water, food and foodstuffs. Ovarian granulosa cells modulate oogenesis by providing metabolic nutrients to oocytes. They can decide the fate of folliculogenesis and oocyte maturation by supplying regulatory cues that help in reproduction. However, little is known about the underlying mechanisms of malathion as a reproductive toxicant in porcine granulosa cells. In the present study, we found that malathion has obvious toxic effects on cultured porcine granulosa cells in a dose-dependent manner. Malathion exposure resulted in significantly increased oxidative stress levels and DNA damage response, which was measured by the mRNA expression levels of homologous recombination (HR) pathway and non-homologous end-joining (NHEJ) pathway-related genes. Subsequently, it was found that malathion exposure could induce apoptosis and autophagy by qRT-PCR and fluorescence intensity analysis. In conclusion, malathion is a reproductive toxicant by inhibiting granulosa cell proliferation by multiple pathways connected to oxidative stress, DNA damage, apoptosis and autophagy.