Casein kinase 1 alpha regulates murine spermatogenesis via p53-Sox3 signaling

Casein kinase 1 alpha (CK1 alpha), acting as one member of the beta-catenin degradation complex, negatively regulates the Wnt/beta-catenin signaling pathway. CK1 alpha knockout usually causes both Wnt/beta-catenin and p53 activation. Our results demonstrated that conditional disruption of CK1 alpha in spermatogonia impaired spermatogenesis and resulted in male mouse infertility. The progenitor cell population was dramatically decreased in CK1 alpha conditional knockout (cKO) mice, while the proliferation of spermatogonial stem cells (SSCs) was not affected. Furthermore, our molecular analyses identified that CK1 alpha loss was accompanied by nuclear stability of p53 protein in mouse spermatogonia, and dual-luciferase reporter and chromatin immunoprecipitation assays revealed that p53 directly targeted the Sox3 gene. In addition, the p53 inhibitor pifithrin alpha (PFT alpha) partially rescued the phenotype observed in cKO mice. Collectively, our data suggest that CK1 alpha regulates spermatogenesis and male fertility through p53-Sox3 signaling, and they deepen our understanding of the regulatory mechanism underlying the male reproductive system.