Scrotal heat induced the Nrf2-driven antioxidant response during oxidative stress and apoptosis in the mouse testis.

The aim of the study was to investigate the response of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant system to elevated scrotal temperature in mouse testes. Eight-week-old mice were exposed to a single scrotal heat treatment (42°C for 25 min). The testes displayed severe damage, with multinucleated giant cells, nuclear condensation and germ cell loss in the seminiferous epithelium. Increased malondialdehyde levels and reduced antioxidant enzyme activities were consistent with an acute oxidative stress response. The number of cleaved caspase 3-positive germ cells per tubule was markedly increased. In addition, scrotal heat caused increased expression of Nrf2 mRNA and translocation of Nrf2 protein into interstitial cell nuclei accompanied by elevated mRNA levels for Nrf2-regulated genes. In conclusion, our data demonstrated the time dependent response of the Nrf2-antioxidant system to a single treatment of scrotal heat in the mouse testes, making this pathway a potential target for new drugs designed to prevent oxidative stress-induced male infertility.