Orisaka Makoto, Jiang Jin-Yi, Orisaka Sanae, Kotsuji Fumikazu, Tsang Benjamin K
Department of Obstetrics and Gynaecology, Reproductive Biology Unit and Division of Reproductive Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Endocrinology. 2009 Jun;150(6):2740-8. doi: 10.1210/en.2008-1536. Epub 2009 Feb 12.
The transition from preantral to early antral stage is the penultimate stage of ovarian follicular development in terms of gonadotropin dependence and follicle destiny. Although oocyte-somatic cell communication is important in early follicular development, our knowledge of the precise role of the oocyte-derived growth differentiation factor (GDF)-9 during preantral follicle growth is incomplete. We examined whether and by what means oocyte-derived GDF-9 controls follicular development and steroidogenesis during the preantral to early antral transition, by a combination of in vitro gene manipulation (i.e. intraoocyte injection of GDF-9 antisense oligos) and preantral follicle culture. Intraoocyte injection of GDF-9 antisense suppressed rat preantral follicle growth in vitro, whereas GDF-9 enhanced follicular development. GDF-9 augmented testosterone production in preantral follicles. GDF-9 antisense suppressed androgen production and CYP17A1 mRNA expression in cultured follicles, a response attenuated by exogenous GDF-9. The nonaromatizable androgen 5alpha-dihydrotestosterone rescued the follicular growth arrest caused by GDF-9 down-regulation. The specific androgen receptor antagonist flutamide suppressed GDF-9-induced preantral follicle growth in vitro. The data suggest that GDF-9 plays an important role in promoting preantral follicle growth by up-regulating follicular androgen biosynthesis. GDF-9 is essential for CYP17A1 expression during follicular development from the preantral to the early antral stage.
从窦前卵泡向早期窦状卵泡的转变，就促性腺激素依赖性和卵泡命运而言，是卵巢卵泡发育的倒数第二个阶段。尽管卵母细胞 - 体细胞通讯在卵泡早期发育中很重要，但我们对卵母细胞衍生的生长分化因子（GDF）-9在窦前卵泡生长过程中的确切作用的了解并不完整。我们通过体外基因操作（即向卵母细胞内注射GDF-9反义寡核苷酸）和窦前卵泡培养相结合的方法，研究了卵母细胞衍生的GDF-9在窦前卵泡向早期窦状卵泡转变过程中是否以及通过何种方式控制卵泡发育和类固醇生成。向卵母细胞内注射GDF-9反义寡核苷酸可在体外抑制大鼠窦前卵泡的生长，而GDF-9则可促进卵泡发育。GDF-9可增加窦前卵泡中睾酮的产生。GDF-9反义寡核苷酸可抑制培养卵泡中的雄激素产生和CYP17A1 mRNA表达，外源性GDF-9可减弱这种反应。不可芳香化的雄激素5α-二氢睾酮可挽救由GDF-9下调引起的卵泡生长停滞。特异性雄激素受体拮抗剂氟他胺可在体外抑制GDF-9诱导的窦前卵泡生长。数据表明，GDF-9通过上调卵泡雄激素生物合成在促进窦前卵泡生长中起重要作用。GDF-9对于从窦前卵泡到早期窦状卵泡发育过程中的CYP17A1表达至关重要。
