CK1α in Sertoli cells is essential for testicular development and spermatogenesis in mice

Male infertility represents a significant global public health issue, with the etiology remaining unidentified in nearly half of the cases. Protein kinase CK1α (CK1α) is a pivotal kinase involved in regulating cell cycle progression, pre-mRNA processing and associated with a complex that contained certain splicing factors. Our recent study indicated that CK1α is expressed in both germ cells and somatic cells within the mouse testes, exerting regulatory control over spermatogenesis. However, the physiological roles and mechanism of CK1α action in mouse Sertoli cell remain elusive. Here, we found that CK1α was highly expressed in Sertoli cells and the conditional knockout of CK1α in murine Sertoli cells resulted in severe testicular atrophy and infertility. The above phenotype was characterized by rapid depletion of Sertoli cells and dysfunction of spermatogenesis. Our findings suggest that CK1α plays a crucial role in regulating the fate determination of fetal and neonatal Sertoli cells in mice. At molecular levels, we found CK1α interacted with a splicing factor ZRSR1 to regulate the apoptosis of Sertoli cells. These findings offer novel insights into the roles of CK1α in alternative splicing (AS) and male reproduction, which are crucial for comprehending the regulatory mechanisms underlying testicular development and male reproductive processes.