Insulin desensitization and cell senescence induced by heat stress in pig testicular cell model

Thermostatic animals need to maintain a stable body temperature. A high-temperature environment can cause body temperature to exceed the range of tolerance of the organism, resulting in a heat stress response. The reproductive organs (such as the testes) are more sensitive to temperature due to their special anatomical location. However, to date, the effect of heat stress on the biological function of insulin in testicular cells has not been revealed. Therefore, the current study established a testis cell model to study the effect of heat stress on the biological activity of insulin. The results showed significant alterations in the insulin-induced intracellular signaling under heat stress conditions. Moreover, the IR-mediated intracellular signaling pathway was significantly downregulated under heat stress conditions. Further studies demonstrated that heat stress led to senescence of testicular cells by Sa-β-gal staining. Furthermore, the expression of senescence markers (p16 and p21) was increased under heat stress. In addition, heat stress was found to cause oxidative stress in testicular cells, which may be the underlying molecular mechanism by which heat stress changes the signaling properties of insulin. Collectively, the current study showed that heat stress caused alterations in insulin-induced intracellular signaling. Heat stress also induced testicular cell senescence.