Beclin1 Regulates Sertoli Cell Function to Maintain Mouse Spermatogenesis

Besides providing nutrients, Sertoli cells support spermatogenic cells development by maintaining seminiferous epithelial polarity, forming the blood-testis barrier (BTB), and phagocytosing residual bodies. Beclin1, a core component of the autophagy initiation complex, is critical for autophagic flux in many cell types. However, its role in Sertoli cells remains unclear. Here, we generated a Sertoli cell-specific Becn1 knockout (cKO) mouse model and found that 9-week-old male cKO mice exhibited reduced fertility with decreased sperm quality and vacuolated seminiferous tubules, and became completely infertile by 12 weeks of age. These defects were associated with disrupted BTB integrity and reduced expression of Claudin-11 in the testes. Further analysis revealed that loss of Beclin1led to impaired autophagosome formation, evidenced by reduced LC3-II/LC3-I ratio. In summary, these findings demonstrate that Beclin1 in Sertoli cells is vital for spermatogenesis and male fertility.