title: Transforming growth factor-β signaling participates in the maintenance of the primordial follicle pool in the mouse ovary.
abstract: 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-β acts on them are poorly understood. So, this study aims to identify whether or not TGF-β acts on the process. Ovary organ culture experiments showed that the culture of 18.5 days post-coitus (dpc) ovaries with TGF-β1 reduced the total population of oocytes and activated follicles, accelerated oocyte growth was observed in ovaries treated with TGF-βR1 inhibitor 2-(5-chloro-2-fluorophenyl)pteridin-4-yl]pyridin-4-yl-amine (SD208) compared with control ovaries, the down-regulation of TGF-βR1 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-β1-treated ovaries. Western blot and morphological analyses indicated that TGF-β 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-β 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.
authors: From the State Key Laboratory of Agro-Biotechnology, College of Biological Science, China Agricultural University, Beijing 100193, People's Republic of China.
authors: Zheng-Pin
authors: ZP
authors: Wang
authors: Xin-Yi
authors: XY
authors: Mu
authors: Meng
authors: M
authors: Guo
authors: Yi-Jing
authors: YJ
authors: Wang
authors: Zhen
authors: Z
authors: Teng
authors: Guan-Ping
authors: GP
authors: Mao
authors: Wan-Bao
authors: WB
authors: Niu
authors: Li-Zhao
authors: LZ
authors: Feng
authors: Li-Hua
authors: LH
authors: Zhao
authors: Guo-Liang
authors: GL
authors: Xia
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism; D009865:Oocytes / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D009924:Organ Culture Techniques; D006080:Ovarian Follicle / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D010053:Ovary / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000076222:Mechanistic Target of Rapamycin Complex 1; D017346:Protein Serine-Threonine Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; D000077293:Receptor, Transforming Growth Factor-beta Type I
keywords: Cell Growth; Mouse; Oocyte; Ovary; Transforming Growth Factor-β (TGFβ)