始基卵泡激活调控的研究进展  

Research progress on the regulation of primordial follicle activation

作　　者：潘静 于潇 刘金星[2] 刘鹏飞 PAN Jing;YU Xiao;LIU Jinxing;LIU Pengfei(The First Clinical College,Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong,China;Gynecology Department,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong,China)

机构地区：[1]山东中医药大学第一临床医学院,山东济南250014 [2]山东中医药大学附属医院妇科,山东济南250014

出　　处：《山东大学学报（医学版）》2024年第8期74-92,100,共20页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金项目(82104917);山东省自然科学基金(ZR2021MH079)。

摘　　要：以早发性卵巢功能不全(premature ovarian insufficiency,POI)为代表的卵巢功能减退性疾病发生的本质是卵巢中卵泡数量的减少或(和)卵泡质量的降低,严重影响女性的生殖健康。卵巢功能减退患者的卵巢中仍然存在部分始基卵泡(primordial follicles,PFs),激活剩余的PFs,使其发育为成熟卵泡,可作为改善卵巢功能的途径之一。PFs是卵泡发育的起点,其休眠和激活的调节是女性维持生育力的重要基础。因此,本文从分子水平探讨PFs激活相关因子及信号通路对卵巢功能的作用机制,重点围绕维持PFs休眠状态的叉头框转录因子O3a(forkhead box O3a,FOXO3a)、叉头框转录因子L2(forkhead box L2,FOXL2)、生殖系α因子(factor in the germline alpha,FIGLA)、LIM同源盒基因8(LIM homeobox 8,LHX8)、精卵发生特异性HLH转录因子1/2(spermatogenesis and oogenesis specific basi chelix-loop-helix transcription factor 1/2,SOHLH1/2)、细胞周期蛋白依赖性激酶抑制物1B(cyclin-dependent kinase inhibitor 1B,CDKN1B)、促进PFs激活的新生儿卵巢同源盒蛋白(newborn ovary homeobox gene,NOBOX)、生长分化因子9(growth differentiation factor 9,GDF9)、骨形态发生蛋白15(bone morphogenetic protein 15,BMP15)、碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)、白血病抑制因子(leukemia inhibitory factor,LIF),以及参与PFs激活调控的PI3K/AKT/FOXO3a、mTOR、Hippo、TGF-β、AMPK、Notch、cAMP和Wnt等信号通路进行系统性总结和阐述,以期为卵巢功能减退性疾病的预防和治疗提供理论依据及潜在药物靶点。Ovarian hypofunction diseases,represented by premature ovarian insufficiency(POI),occurs when the number or/and the quality of the follicles in the ovaries decrease,which seriously affects womens reproductive health.Some primordial follicles(PFs)still exist in the ovaries of patients with hypofunction diseases,and activation of the remaining PFs to mature follicles can be one of the ways to improve ovarian function.PFs are the starting point of follicular development,and the regulation of their dormancy and activation is an important basis for the maintenance of female fertility.This article systematically reviews and elucidates the molecular mechanisms underlying the activation of PFs,focusing on key factors such as forkhead box O3a(FOXO3a),forkhead box L2(FOXL2),factor in the germline alpha(FIGLA),LIM homeobox 8(LHX8),spermatogenesis and oogenesis specific basic helix-loop-helix transcription factors 1/2(SOHLH1/2),cyclin-dependent kinase inhibitor 1B(CDKN1B/p27 Kip1),newborn ovary homeobox gene(NOBOX),growth differentiation factor 9(GDF9),bone morphogenetic protein 15(BMP15),basic fibroblast growth factor(bFGF/FGF2),and leukemia inhibitory factor(LIF).These factors play either a positive or negative role in primordial follicle activation.Additionally,the article discusses various signaling pathways involved in regulating primordial follicle activation,including PI3K/AKT/FOXO3a,mTOR,Hippo,TGF-β,AMPK,Notch,cAMP,and Wnt signaling pathways.This review aims to provide a theoretical foundation and identify potential drug targets for the prevention and treatment of ovarian hypofunction diseases.

关 键 词：卵巢功能减退性疾病 始基卵泡激活 抑制因子 促进因子 信号通路 

分 类 号：R711.75[医药卫生—妇产科学]