| First Author | Wang ZP | Year | 2014 |
| Journal | J Biol Chem | Volume | 289 |
| Issue | 12 | Pages | 8299-311 |
| PubMed ID | 24515103 | Mgi Jnum | J:212442 |
| Mgi Id | MGI:5581399 | Doi | 10.1074/jbc.M113.532952 |
| Citation | Wang ZP, et al. (2014) Transforming growth factor-beta signaling participates in the maintenance of the primordial follicle pool in the mouse ovary. J Biol Chem 289(12):8299-311 |
| abstractText | Physiologically, only a few primordial follicles are activated to enter the growing follicle pool each wave. Recent studies in knock-out mice show that early follicular activation depends on signaling from the tuberous sclerosis complex, the mammalian target of rapamycin complex 1 (mTORC1), phosphatase and tensin homolog deleted on chromosome 10, and phosphatidylinositol 3-kinase (PI3K) pathways. However, the manner in which these pathways are normally regulated, and whether or not TGF-beta acts on them are poorly understood. So, this study aims to identify whether or not TGF-beta acts on the process. Ovary organ culture experiments showed that the culture of 18.5 days post-coitus (dpc) ovaries with TGF-beta1 reduced the total population of oocytes and activated follicles, accelerated oocyte growth was observed in ovaries treated with TGF-betaR1 inhibitor 2-(5-chloro-2-fluorophenyl)pteridin-4-yl]pyridin-4-yl-amine (SD208) compared with control ovaries, the down-regulation of TGF-betaR1 gene expression also activated early primordial follicle oocyte growth. We further showed that there was dramatically more proliferation of granulosa cells in SD208-treated ovaries and less proliferation in TGF-beta1-treated ovaries. Western blot and morphological analyses indicated that TGF-beta signaling manipulated primordial follicle growth through tuberous sclerosis complex/mTORC1 signaling in oocytes, and the mTORC1-specific inhibitor rapamycin could partially reverse the stimulated effect of SD208 on the oocyte growth and decreased the numbers of growing follicles. In conclusion, our results suggest that TGF-beta signaling plays an important physiological role in the maintenance of the dormant pool of primordial follicles, which functions through activation of p70 S6 kinase 1 (S6K1)/ribosomal protein S6 (rpS6) signaling in mouse ovaries. |
