Transforming growth factor-ß signaling participates in the maintenance of the primordial follicle pool in the mouse ovary.

The Journal of biological chemistry

PubMedID: 24515103

Wang ZP, Mu XY, Guo M, Wang YJ, Teng Z, Mao GP, Niu WB, Feng LZ, Zhao LH, Xia GL. Transforming growth factor-ß signaling participates in the maintenance of the primordial follicle pool in the mouse ovary. J Biol Chem. 2014;.
Physiologically, only a few primordial follicles are activated to enter the growing follicle pool each wave. Recent studies in knockout mice show that early follicular activation depends on signaling from the tuberous sclerosis complex (TSC), the mammalian target of rapamycin complex 1 (mTORC1), phosphatase and tensin homolog deleted on chromosome 10 (PTEN), and phosphatidylinositol 3 kinase (PI3K) pathways. However, the manner in which these pathways are normally regulated, and whether or not TGF-ß acts on them are poorly understood. So, this study aims to identify whether or not TGF-ß acts on the process. Ovary organ culture experiments showed that the culture of 18.5-days post-coitus (dpc) ovaries with TGF-ß1 reduced the total population of oocytes and activated follicles, accelerated oocyte growth was observed in ovaries treated with TGF-ßR1 inhibitor 2-(5-Chloro-2-fluorophenyl)pteridin-4-yl]pyridin-4-yl-amine (SD208) compared to control ovaries, the downregulation of TGF-ßR1 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-ß1-treated ovaries. Western blot and morphological analyses indicated that TGF-ß signaling manipulated primordial follicle growth through TSC/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-ß 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.