Growth differentiation factor 9 is antiapoptotic during follicular development from preantral to early antral stage
Growth differentiation factor 9 is antiapoptotic during follicular development from preantral to early antral stage
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DOI：
10.1210/me.2005-0357
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发表时间：
2006-10-01
影响因子：
--
通讯作者：
Tsang, Benjamin K.
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文献类型：
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作者：
Orisaka, Makoto;Orisaka, Sanae;Tsang, Benjamin K.
卵巢卵泡闭锁代表了一个选择过程，确保在排卵期间只释放健康和有活力的卵母细胞。就促性腺激素依赖性和卵泡命运（存活/生长vs.闭锁）而言，从窦前期到早期窦期的过渡是发育的倒数第二个阶段。我们研究了卵母细胞衍生的生长分化因子9（GDF-9）和FSH是否以及如何调节卵泡发育和闭锁在窦前到早期窦过渡，通过一种新的组合，在体外基因操作（即卵母细胞内注射GDF-9反义寡核苷酸）和窦前卵泡培养。在体外，注射GDF-9反义抑制基础和FSH诱导的腔前卵泡生长，而添加GDF-9增强基础和FSH诱导的卵泡发育。GDF-9反义激活caspase-3并诱导培养的腔前卵泡凋亡，外源性GDF-9减弱了这种反应。GDF-9增加早期窦卵泡颗粒细胞磷酸化Akt含量。虽然神经酰胺诱导的颗粒细胞凋亡被GDF-9的存在所减弱，但GDF-9的这种保护作用被磷脂酰肌醇3-激酶抑制剂LY 294002和Akt的显性负性形式所阻止。注射GDF-9反义降低了培养卵泡中FSH受体mRNA的水平，这种反应可通过外源性GDF-9的存在来预防。这些数据表明，GDF-9在腔前卵泡中具有抗凋亡作用，并通过激活磷脂酰肌醇3-激酶/Akt途径保护颗粒细胞免于凋亡。卵泡FSH受体mRNA表达需要足够水平的GDF-9。GDF-9通过抑制颗粒细胞凋亡和卵泡闭锁促进窦前至早期窦过渡期间的卵泡存活和生长。
Ovarian follicular atresia represents a selection process that ensures the release of only healthy and viable oocytes during ovulation. The transition from preantral to early antral stage is the penultimate stage of development in terms of gonadotropin dependence and follicle destiny (survival/growth vs. atresia). We have examined whether and how oocyte-derived growth differentiation factor 9 (GDF-9) and FSH regulate follicular development and atresia during the preantral to early antral transition, by a novel combination of in vitro gene manipulation (i.e. intraoocyte injection of GDF-9 antisense oligos) and preantral follicle culture. Injection of GDF-9 antisense suppressed basal and FSH- induced preantral follicle growth in vitro, whereas addition of GDF-9 enhanced basal and FSH-induced follicular development. GDF-9 antisense activated caspase-3 and induced apoptosis in cultured preantral follicles, a response attenuated by exogenous GDF-9. GDF-9 increased phospho-Akt content in granulosa cells of early antral follicles. Although granulosa cell apoptosis induced by ceramide was attenuated by the presence of GDF-9, this protective effect of GDF-9 was prevented by the phosphatidylinositol 3-kinase inhibitor LY294002 and a dominant negative form of Akt. Injection of GDF-9 antisense decreased FSH receptor mRNA levels in cultured follicles, a response preventable by the presence of exogenous GDF-9. The data suggest that GDF-9 is antiapoptotic in preantral follicles and protects granulosa cells from undergoing apoptosis via activation of the phosphatidylinositol 3-kinase/Akt pathway. An adequate level of GDF-9 is required for follicular FSH receptor mRNA expression. GDF-9 promotes follicular survival and growth during the preantral to early antral transition by suppressing granulosa cell apoptosis and follicular atresia.