| First Author | Zhang D | Year | 2024 |
| Journal | Biol Reprod | Volume | 110 |
| Issue | 2 | Pages | 246-260 |
| PubMed ID | 37944068 | Mgi Jnum | J:345641 |
| Mgi Id | MGI:7610343 | Doi | 10.1093/biolre/ioad144 |
| Citation | Zhang D, et al. (2024) CK1alpha deficiency impairs mouse uterine adenogenesis by inducing epithelial cell apoptosis through GSK3beta pathway and inhibiting Foxa2 expression through p53 pathway. Biol Reprod 110(2):246-260 |
| abstractText | Uterine glands and their secretions are crucial for conceptus survival and implantation in rodents and humans. In mice, the development of uterine gland known as adenogenesis occurs after birth, whereas the adenogenesis in humans initiates from fetal life and completed at puberty. Uterine adenogenesis involves dynamic epithelial cell proliferation, differentiation, and apoptosis. However, it is largely unexplored about the mechanisms governing adenogenesis. CK1alpha plays important roles in regulating cell division, differentiation, and death, but it is unknown whether CK1alpha affects adenogenesis. In the current study, uterus-specific CK1alpha knockout female mice (Csnk1a1d/d) were infertile resulted from lack of uterine glands. Subsequent analysis revealed that CK1alpha deletion induced massive apoptosis in uterine epithelium by activating GSK3beta, which was confirmed by injections of GSK3beta inhibitor SB216763 to Csnk1a1d/d females, and the co-treatment of SB216763 and CK1 inhibitor d4476 on cultured epithelial cells. Another important finding was that our results revealed CK1alpha deficiency activated p53, which then blocked the expression of Foxa2, an important factor for glandular epithelium development and function. This was confirmed by that Foxa2 expression level was elevated in p53 inhibitor pifithrin-alpha injected Csnk1a1d/d mouse uterus and in vitro dual-luciferase reporter assay between p53 and Foxa2. Collectively, these studies reveal that CK1alpha is a novel factor regulating uterine adenogenesis by inhibiting epithelial cell apoptosis through GSK3beta pathway and regulating Foxa2 expression through p53 pathway. Uncovering the mechanisms of uterine adenogenesis is expected to improve pregnancy success in humans and other mammals. |
