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

Male infertility constitutes a major global public health concern, with the underlying etiology remaining unidentified in nearly half of the diagnosed cases. Protein kinase CK1α (CK1α) functions as a pivotal regulator of cell cycle progression, pre-mRNA processing, and spliceosome-associated pathways through interactions with specific splicing factors. Comprehensive analyses revealed CK1α expression in both germ cells and somatic cells of mouse testes, implicating its involvement in spermatogenic regulation. However, the physiological roles and mechanistic basis of CK1α function in Sertoli cells remain unclear. In this study, CK1α was highly expressed in Sertoli cells, and conditional knockout of CK1α in murine Sertoli cells induced profound testicular atrophy and complete infertility. This phenotype was characterized by rapid depletion of Sertoli cells and spermatogenic dysfunction. Subsequent analyses demonstrated that CK1α regulated the fate determination of fetal and neonatal Sertoli cells in mice. At the molecular level, CK1α promoted Sertoli cell survival through interaction with the splicing factor ZRSR1 to modulate apoptosis. Collectively, these findings establish CK1α as a key regulator of alternative splicing and male reproduction, providing critical insights into the molecular mechanisms underlying testicular development and reproductive function.