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[摘要] 抑制素(inhibin,INH)是转化生长因子β超家族成员之一,有抑制素A(INH-A)和抑制素B(INH-B)两种形式。在女性,INH-B由卵巢中、小窦卵泡颗粒细胞产生,具有反馈性抑制垂体卵泡刺激素(FSH)分泌和调节生殖细胞发育的重要功能,可直接反映卵巢储备。抑制素B的监测在女性生殖及辅助生殖技术中的应用有重要意义。
[关键词] 抑制素B;卵巢储备;辅助生殖技术;女性生殖
[中图分类号] R711[文献标识码] A [文章编号] 1673-9701(2010)04-45-02
近20年来,对INH在生殖内分泌领域的作用有了日益深入的认识,INH-B由生殖细胞分泌产生,与生殖能力有密切关系,参与女性卵泡发育调控及男性精子的发生,本文现对INH-B与女性生殖的关系作一综述。
1INHB概述
抑制素(inhibin,inh)是生殖细胞分泌的糖蛋白激素,属于转化生长因子β家族,主要包括INHA和INH-B(分别由α和βA或βB亚基构成)。女性体内INH-B在窦前卵泡期即开始分泌,主要由中、小窦卵泡的颗粒细胞合成,颗粒细胞呈脉冲式(60～70min/次)分泌的INH-B进入卵泡液发挥自分泌和旁分泌作用,并由卵巢静脉进入循环。INH-B的分泌主要受FSH的调节,FSH促进颗粒细胞分泌INH-B,另外胰岛素样生长因子I(IGF-I)、激活素能上调INH-B的分泌;而表皮生长因子(EGF)、转化生长因子α(TGF-α)、IGF-II和卵泡抑素(follistatin,FS)则抑制INH-B的分泌[1]。在女性月经周期的卵泡期中,除E2起关键作用外,孕酮和INHB也分别控制着LH及FSH的分泌[2],INH-B的主要生理作用是反馈性抑制垂体FSH的分泌,并通过旁分泌/自分泌调节作用增加E2底物的产生,从而调节E2的分泌。
女性正常月经周期中,血清INH-B水平在早卵泡期缓慢而稳定的上升,卵泡中期达到高峰,然后于卵泡晚期和排卵前开始下降。排卵后由于卵泡破裂INH-B释放入血再次出现高峰,之后迅速下降,于整个黄体期持续低水平[3]。
2抑制素B与女性生殖
2.1INH-B与卵巢储备
卵巢储备能力是指卵巢皮质区卵泡生长、发育、形成可受精的卵母细胞的能力,是由卵巢内存留的卵泡数量和质量决定的,反映女性生育能力。目前用于评价卵巢储备功能的指标有年龄、基础FSH、基础E2、FSH/LH比值、克罗米芬刺激试验、GnRH-a刺激试验、外源性FSH刺激试验以及基础卵巢体积、基础窦卵泡数、抗苗勒管激素等。INH水平与卵巢储备功能的关系已越来越受到关注。Seifer等[4]认为,卵巢窦卵泡颗粒细胞分泌的INH-B可作为卵巢储备功能的直接指标,而垂体分泌的FSH仅为间接指标,对109例非卵巢因素不孕者和47例卵巢储备功能下降者研究发现,卵巢储备功能减退妇女的月经第3天血清INH-B下降先于FSH升高,因此可以通过月经第3天血清INH-B浓度的变化来判断有无卵巢储备功能减退。评价卵巢储备下降的基础INH-B值目前尚无统一标准,文献报道大多为40IU/L、E214mm)取卵数、受精率高度相关。认为INH-B对促排卵效果具有预测价值。Eldar-Geva等[17]发现INH-B与取卵数呈正相关,推论在采用固定剂量FSH促排卵的早期测定血清INH-B,能较早推测募集卵泡中长至成熟卵泡的数目。
众多研究表明,基础INHB水平与成熟卵泡数目高度相关,还能预测IVF获卵数目,与受精率高度相关。在促排卵早期就可根据INHB的变化预计该周期获卵情况,及时调整Gn用量。
2.3.3INH-B与IVF结局Urbancsek等[18]对110名接受IVF或ICSI助孕的患者进行病例对照研究,认为促排卵日INH-B不是一个较好的预测IVF结局的指标,取卵日高INH-B是独立于年龄、E2峰、获卵数和胚胎数的较好的预测临床妊娠的指标。而Hall等[19]认为年龄和获卵数是妊娠的最强预测指标,INH-B值在妊娠和非妊娠组有较大重叠,只能反映卵巢储备,不能作为预测妊娠的独立指标,只有较低的基础FSH和较高的基础INH-B结合起来,才对妊娠有预测价值。另有学者将使用Gn3d后INHB与月经周期第二天INHB的差值作为ΔINH-B,发现早在促排卵3d,ΔINHB即与获卵数呈线性正相关,当ΔINH-B 总之,由颗粒细胞分泌的INH-B直接反应着卵巢的储备功能,参与了女性生殖过程的精确调控,动态监测INH-B水平,对明确女性生殖相关疾病的发生发展,对接受ART治疗患者的用药指导、改善妊娠结局等有重要作用。
[参考文献]
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(收稿日期:2009-12-04)
