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, critical for 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. The involvement of SIRT1 has been documented in multiple key biological processes; however, its role in Sertoli cells remains unknown.

METHODS

This study involved isolation of yak Sertoli cells to examine the impact of SIRT1 on cell viability and its related regulatory mechanisms using RNA interference (RNAi).

RESULTS

The findings revealed that SIRT1 knockdown significantly impaired the viability and function of yak Sertoli cells. Transcriptome sequencing indicated a significant impact on mitochondrial structure following SIRT1 knockdown. Subsequent studies demonstrated that knockdown of SIRT1 in yak Sertoli cells led to significant downregulation of genes related to mitochondrial morphology, a reduction in membrane potential, decreased expression of mitochondrial genes, and a diminished capacity for ATP synthesis. The PGC-1α-NRF-1-TFAM pathway, a key signaling cascade in mitochondrial biogenesis, was inhibited after SIRT1 knockdown. The overexpression of PPARGC1A in SIRT1-knockdown yak Sertoli cells partially rescued the reduction in cell viability and the impairment of mitochondrial biogenesis. These findings indicate that SIRT1 regulates mitochondrial biogenesis in yak Sertoli cells through the activation of the PGC-1α-NRF-1-TFAM signaling pathway, thereby maintaining cellular viability.

CONCLUSION

The present study 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.