Involvement of NRF2 in Perfluorooctanoic Acid-Induced Testicular Damage in Male Mice1

Perfluorooctane acid (PFOA) is a hazardous environmental pollutant that has been reported to exert adverse effects on animal and human health. In this study, male mice were orally administered different concentrations of PFOA (2.5, 5, or 10 mg/kg/day) to evaluate the reproductive toxicity. Exposure to PFOA for 14 consecutive days obviously disrupted seminiferous tubules and reduced sperm count. The highest concentration of PFOA (10 mg/kg/day) caused growth retardation and diminished absolute testis weight. Furthermore, PFOA treatment significantly increased the generation of oxidative stress indicators malondialdehyde and hydrogen peroxide, decreased the expression of transcription factor NRF2, and inhibited the activities of antioxidant enzymes superoxide dismutase and catalase in the testis. Moreover, PFOA exposure up-regulated p-p53 and BAX expression and down-regulated BCL-2 expression in the testis. These results indicated that PFOA-induced male reproductive disorders might be involved in developmental impairment and inhibition of NRF2-mediated antioxidant response in the testis of mice.