参与调控始基卵泡激发过程的细胞信号通路  

Cell signaling pathways involved in the regulation of primordial follicle stimulating processes

作　　者：王凤伟[1] 王静芬[1] 徐键[1] 

机构地区：[1]浙江大学医学院附属妇产科医院,杭州310006

出　　处：《生殖与避孕》2016年第3期208-213,239,共7页Reproduction and Contraception

基　　金：国家科技支撑计划项目(No.2012BAI32B00);国家自然科学基金项目(No.81270663);浙江省中医药重点研究项目(No.2014ZZ008)

摘　　要：始基卵泡占卵巢所有卵泡的99%以上,人卵巢组织中最后一批由初级卵母细胞分化形成的始基卵泡的寿命可长达50余年。始基卵泡的有序激活受多种信号通路的调控作用。许多细胞因子可以通过PI3K-AKT信号通路,激活叉头蛋白转录因子O3a(Fox O3a),促进始基卵泡的启动,而该作用可以被抑癌基因PTEN编码的蛋白所抑制;结节性硬化综合征(TSC)蛋白能够负向调节哺乳动物雷帕霉素靶蛋白复合体1(m TORC1),在始基卵泡保持静止状态的过程中发挥重要作用;转化生长因子-β(TGF-β)家族成员众多,对始基卵泡的激活作用存在争议,主要通过蛋白分子Smads控制靶基因的转录;近期有研究表明,Hippo信号通路在卵泡激活调节过程中有重要作用,对卵巢组织进行机械切割,可以抑制Hippo信号通路,促进卵泡激活。上述不同的信号通路之间存在频繁的交叉对话。对多种信号通路之间进行联系,能够为整体理解始基卵泡的激活机制提供新的思路。Primordial follicle accounts for more than 99% of all ovarian follicles. The last batch of primordial follicles formed by primary oocytes can survive more than 50 years. Multiple signaling pathways regulate the orderly activation of primordial follicles. Many cytokines can activate forkhead box group O3a （FoxO3a） via PI3K-AKT signaling pathway and promote the activation of primordial follicles. This effect can be inhibited by phosphatase and tensin homolog （PTEN）. The tumor suppressor tuberous sclerosis complex 1 （Tsc1）, which negatively regulates mammalian target of rapamycin complex 1 （mTORC 1）, functions in oocytes to maintain the quiescence of primordial follicles. Transforming growth factor beta （TGF-β） super family includes many family members, which can control the transcription of target genes through protein Smads. Its role in follicle stimulation is controversial. The recent studies have shown that mechanical cutting of ovarian tissue can inhibit the Hippo signal pathway and promote follicular activation. There are frequent cross talks between the different signal pathways. The link between multiple signaling pathways can provide a new train of thought for us to overall understand the primordial follicle activation mechanism.

关 键 词：卵泡激发 PTEN/PI3K/AKT信号通路 TSC/mTORC1信号通路 转化生长因子(TGF)-γ信号通路 Hippo信号通路 

分 类 号：R339.22[医药卫生—人体生理学]