Perfluorooctanoic acid exposure disrupt the mitochondrial electron transport chain of granulosa cells leads to defect in follicular development

Perfluorooctanoic acid (PFOA) is a kind of perfluorinated alkyl substances (PFASs), commonly used in daily life as a surfactant, which persists in soil and water, finally enters and accumulates in the organisms through food and drinking water. It has been reported that PFOA can accumulate in human ovarian follicle and impar the ovarian function as an environmental disturbance. However, the detailed mechanism of PFOA interfering ovarian function is far from being elucidated and there are few effective treatments. Here, we established a PFOA exposure mouse model by drinking water intake and found that the follicle development of mice were impaired with increased apoptosis of granulosa cells (GCs). We introduced an in vitro 3D follicle culture system to simulate PFOA exposure in vivo, and the results also confirmed that PFOA hinder the normal development of follicles. Further RNA-seq analysis showed that oxidative phosphorylation is significantly impaired in PFOA exposure ovary due to disruption of the mitochondrial electron transport chain. The mitochondrial membrane potential of isolated GCs or KGN cell line were impaired, and the level of mitochondrial reactive oxygen species (mtROS) was increased. In addition, mitochondrial nutrient supplement, CoQ10 can improve cellular mitochondrial function and restore normal follicular development. In summary, our results indicated that PFOA exposure impair the mitochondrial function of GCs and increase the level of mtROS, thus affecting the development of follicle. CoQ10 can restore normal follicular development during PFOA exposure.