Dysregulation of NrF2 expression mediates testicular injury and infertility in 3-monochloro-1,2-propandiol-intoxicated rats with special reference to accessory gland-related pathology.

3-Monochloropropane-1,2-diol (3-MCPD) is a food contaminant formed during acid hydrolysis of vegetable proteins. The toxicological evaluation of smaller doses of 3-MCPD is essential for safety evaluation of this compound. The present study investigates the toxicologic potential of 3-MCPD on male genital organs of rats, applies a correlation between the induced infertility and developed lesions in testes, epididymis, and accessory glands and study the possible mechanisms of 3-MCPD-induced male infertility. Forty rats were randomly divided into four main groups of ten animals each: the control untreated group and three treated groups that were orally administered 3-MCPD at different doses (3, 7.5 and 15 mg/kg b.w) daily via stomach intubation for five successive days per week. Five rats from each group were euthanized after 30 days. The remaining rats were euthanized after 90 days to establish subacute and chronic toxicity studies. Oxidative stress markers, Nrf2 gene expression, semen analysis, and histopathological examination were performed at the end of each experimental period. Results indicated that 3-MCPD induces infertility in male rat via disruption of Nrf2 expression in the testicular tissue with subsequent increased oxidative stress indicators in the testis that affect spermatogenesis and induced testicular degeneration, in addition, induction of epididymal lesions that affect sperm motility and concentration and finally possible development of hyperplastic tissue reactions in accessory glands of intoxicated rats predicting the carcinogenic potential of this compound.