Tert-butylhydroquinone attenuates scrotal heat-induced damage by regulating Nrf2-antioxidant system in the mouse testis

• tBHQ induced mild oxidative stress in mouse testis.
• tBHQ inhibited testosterone synthesis.
• Both tBHQ and scrotal heat activated Nrf2-antioxidant system.
• Pretreated tBHQ attenuated scrotal heat-induced damage.

Tert-butylhydroquinone (tBHQ), a widely used nuclear factor erythroid 2-related factor 2 (Nrf2) activator, was always employed to investigate the potential protective role of Nrf2 activation. In this study, to elucidate the effect of tBHQ on scrotal heat-induced damage and Nrf2-antioxidant system in mouse testes, eight-week-old mice were administrated with or without dietary tBHQ (1% w/w) for 1 week and afterward subjected to a single scrotal heat treatment (42 °C for 25 min). Trunk blood and testes were collected 3 h or 1, 2, or 7 days later. Mice displayed less germ cell loss in testes, higher relative testis weight and lower testosterone concentration on day 2 in tBHQ treatment group. Before heat treatment, there were significant increases in malondialdehyde (MDA) concentration in tBHQ treatment group. After heat treatment, mice in tBHQ treatment group showed lower MDA concentration than those in non-tBHQ treatment group. In addition, both tBHQ pretreatment and scrotal heat treatment induced markedly increased Nrf2 protein expression in cytoplasm and nuclei of interstitial cells, accompanying with elevated mRNA expression of Nrf2 and Nrf2-regulated genes in mice testes. Our data indicated that pretreatment to tBHQ induced a mild oxidative stress, and further enhanced the cellular antioxidative ability to protect testicular cells against scrotal heat-induced damage via a mechanism that might involve the Nrf2-antioxidant system in mice testes.