摘要
卵巢早衰(POF)是指女性在40岁前发生卵巢功能衰退的一种病理状态,与生育力下降、骨质疏松及心血管疾病风险升高等密切相关,已成为影响女性生殖健康和生活质量的重要临床问题。目前研究表明,颗粒细胞(GC)作为卵泡微环境中的关键细胞,其异常凋亡可加速卵泡闭锁,从而参与POF的发生与发展进程。近年来,随着分子生物学与组学技术的发展,GC凋亡的机制研究逐步深入。研究表明,其调控涉及多层面因素:在蛋白水平上,BCL-2家族与Caspase级联反应构成凋亡执行的核心模块;在信号通路层面,Wnt/β-catenin、死亡受体通路、Hippo、PI3K/AKT/mTOR等通路通过交叉对话协同调控GC凋亡;此外,表观遗传修饰、氧化应激、激素失衡及炎症微环境等因素也共同参与GC凋亡的启动与进展。因此,本文通过系统综述GC凋亡相关信号通路、关键蛋白及潜在调控机制,深入阐明其在POF发生发展中的作用,为解析POF的病理机制提供新的理论视角,并为未来开发靶向调控GC凋亡的干预策略提供参考依据。
Premature ovarian failure(POF)is a pathological condition characterised by the decline of ovarian function in women under the age of 40.It is closely associated with decreased fertility,elevated risks of osteoporosis and cardiovascular diseases,and has emerged as a significant clinical issue affecting women's reproductive health and quality of life.Current research indicates that granulosa cell(GC),as key components of the follicular microenvironment,can accelerate follicular atresia through abnormal apoptosis,thereby contributing to the onset and progression of POF.In recent years,advances in molecular biology and omics technologies have facilitated deeper investigation into the mechanisms of GC apoptosis.Studies have revealed that its regulation involves multi‑level factors:at the protein level,the BCL‑2 family and the Caspase cascade constitute the core module of apoptosis execution;at the signaling pathway level,pathways such as Wnt/β‑catenin,death receptor signaling,Hippo,and PI3K/AKT/mTOR interact through crosstalk to coordinately regulate GC apoptosis.In addition,epigenetic modifications,oxidative stress,hormonal imbalances,and inflammatory microenvironments collectively contribute to the initiation and progression of GC apoptosis.Hence,this review systematically summaries the signaling pathways,key proteins,and underlying regulatory mechanisms related to GC apoptosis,to elucidate its role in the pathogenesis of POF.This work seeks to provide novel theoretical perspectives on the pathological mechanisms of POF and to offer a reference for developing targeted intervention strategies aimed at regulating GC apoptosis.
作者
周敏
满奕村
罗思琪
王青
谢蕙霞
吕群
ZHOU Min;MAN Yicun;LUO Siqi;WANG Qing;XIE Huixia;LYU Qun(School of Medicine,University of Electronic Science and Technology of China,Chengdu 610075,China;Reproductive Center,Sichuan Academy of Medical Sciences&Sichuan Provincial People's Hospital,Chengdu 610075,China;School of Medicine and Life Sciences,Chengdu University of Traditional Chinese Medicine,Chengdu 610075,China)
出处
《医学新知》
2026年第2期224-230,共7页
New Medicine
基金
四川省中医药管理局中医药科研专项课题(2023MS307)。
关键词
卵巢早衰
颗粒细胞
凋亡
分子机制
治疗
Premature ovarian failure
Granulosa cell
Apoptosis
Molecular mechanisms
Therapy
