| First Author | Wen J | Year | 2019 |
| Journal | BMC Biol | Volume | 17 |
| Issue | 1 | Pages | 23 |
| PubMed ID | 30866939 | Mgi Jnum | J:291552 |
| Mgi Id | MGI:6444924 | Doi | 10.1186/s12915-019-0641-9 |
| Citation | Wen J, et al. (2019) GSK-3beta protects fetal oocytes from premature death via modulating TAp63 expression in mice. BMC Biol 17(1):23 |
| abstractText | BACKGROUND: Female mammals have a limited reproductive lifespan determined by the size of the primordial follicle pool established perinatally. Over two thirds of fetal oocytes are abolished via programmed cell death during early folliculogenesis. However, the underlying mechanisms governing fetal oocyte attrition remain largely elusive. RESULTS: Here, we demonstrate that glycogen synthase kinase-3 beta (GSK-3beta) is indispensable for fetal oocyte maintenance during meiotic prophase I in mice. In vitro inhibition of GSK-3beta activity or in vivo conditional deletion of Gsk-3beta in the germline led to a dramatic loss of fetal oocytes via apoptosis, which subsequently resulted in a reduced capacity of the primordial follicle pool. Inhibition of GSK-3beta also impeded meiotic progression in fetal oocytes and led to a deficiency in DNA double-strand break (DSB) repair associated with premature upregulation of Tap63, the major genome guardian of the female germline, following GSK-3beta inhibition in fetal ovaries. Mechanistically, we demonstrated that aberrant nuclear translocation of beta-catenin was responsible for the abnormal expression of TAp63 and global fetal oocyte attrition following GSK-3beta inhibition. CONCLUSIONS: In summary, GSK-3beta was essential for sustaining fetal oocyte survival and folliculogenesis via fine-tuning the cytoplasmic-nuclear translocation of beta-catenin, which in turn modulates timely TAp63 expression during meiotic prophase I in mice. Our study provides a perspective on the physiological regulatory role of DNA damage checkpoint signaling in fetal oocyte guardianship and female fertility. |
