ATP alleviates heat stress-induced suppression of proliferation and enhancement of apoptosis by inhibiting the activation of AMPK/mTORC1 signaling in the Sertoli cells of dairy bulls.

Sertoli cells (SCs), as essential somatic cells in the testes of dairy bulls, offer both structural and nutrient assistance to developing germ cells while interacting directly with them to regulate spermatogenesis. AMP-activated protein kinase (AMPK) functions as an essential regulator of energy metabolism in the testis. However, the regulatory function of AMPK in maintaining SC viability during heat stress conditions is unclear. Recent research has focused on the protective function of ATP in the modulation of SC enhancement of apoptosis and suppression of proliferation under heat stress conditions through AMPK/mTORC1 signaling. The present study demonstrated that heat stress significantly suppressed cell proliferation and increased apoptosis in SCs. ATP pretreatment also prevented heat stress-related decreases in the mitochondrial membrane potential and mRNA expression levels of PCNA and KI67 (both are markers of cell proliferation and indicate the proliferation status of cells through different mechanisms). Moreover, ATP treatment reversed the effects of heat stress on cell proliferation and apoptosis, and ATP treatment increased cell viability by alleviating the expression of the AMPK/mTORC1 signaling-related components in heat stress-induced SCs. In summary, these findings indicate that AMPK/mTORC1 signaling is involved in the regulation of apoptosis and proliferation in SCs during heat stress and that the protective effects of ATP therapy on SCs provide a theoretical basis for preventing heat stress injury in the testes of dairy bulls.