SIRT1 plays a critical role in maintaining the viability of Yak Sertoli cells by regulating mitochondrial biogenesis via activating the PGC-1α-NRF-1-TFAM pathway

Objective: Sertoli cells are somatic cells located within the seminiferous tubules that play a critical role in spermatogenesis through various mechanisms, such as paracrine signaling and the formation of the blood-testis barrier. Sirtuin 1 (SIRT1), a member of the evolutionarily conserved sirtuin family, is an NAD⁺-dependent class III histone deacetylase. SIRT1 involvement has been documented in multiple key biological processes; however, its role in Sertoli cells remains unknown. Methods: In this study, yak Sertoli cells were isolated, and the impact of SIRT1 on cell viability and its related regulatory mechanisms was investigated using RNA interference (RNAi). Results: The findings revealed that after SIRT1 knockdown, the viability and function of yak Sertoli cells were significantly impaired. Transcriptome sequencing revealed a significant impact on mitochondrial structure following SIRT1 knockdown. Further studies demonstrated that knockdown of SIRT1 in yak Sertoli cells led to significant downregulation of genes related to mitochondrial morphology, reduced membrane potential, decreased mitochondrial gene expression, and diminished ATP synthesis capacity. The PGC-1α-NRF-1-TFAM pathway, a key signaling cascade in mitochondrial biogenesis, was inhibited after SIRT1 knockdown. Overexpression of PGC-1α in SIRT1-knockdown yak Sertoli cells rescued the decline in cell viability and impaired mitochondrial biogenesis to some extent. These findings indicate that SIRT1 regulates mitochondrial biogenesis in yak Sertoli cells by activating the PGC-1α-NRF-1-TFAM signaling pathway, thereby maintaining cellular viability. Conclusion: The present study preliminarily elucidates the regulatory role and mechanism of SIRT1 in yak Sertoli cells, providing fundamental data and new insights for further research on the function of SIRT1 in reproductive regulation in yaks.