Oocyte Casein kinase 1α deletion causes defects in primordial follicle formation and oocyte loss by impairing oocyte meiosis and enhancing autophagy in developing mouse ovary

Abstract Casein kinase1α is a member of CK1 family, which is ubiquitously expressed and plays multiple functions, including its potential roles in regulating cell division. But the functions of CK1α in mammalian oogenesis and folliculogenesis remain elusive. In this study, we firstly assayed the cell type of CK1α expression in the developing mouse ovary and confirmed that CK1α highly expressed in oocyte. The oocyte-specific CK1α knockout (cKO) mouse model was then established by crossing Ddx4-Cre mice with Csnk1a1-floxp mice, and the effects of CK1α deletion on oogenesis and folliculogenesis were identified. The results showed that oocyte CK1α deletion impaired the progression of oocyte meiosis and primordial follicle formation during meiotic prophase I, which subsequently causes oocyte loss and mouse infertility. Further, the in vivo CK1α deletion and in vitro CK1α activity inhibition resulted in the defects of DNA double-strand break (DSB) repair, whereas the apoptosis and autophagy were enhanced in the developing ovary. These may contribute to the oocyte loss and infertility in cKO mouse. It is thus concluded that CK1α is an essential factor for mouse oogenesis and folliculogenesis by involving in regulating the processes of oocyte meiosis and DNA DSB repair during meiotic prophase I of oocytes, although the related signaling pathway and the molecular mechanism need to be elucidated further.