铁死亡与早发性卵巢功能不全的关系

doi:10.12280/gjfckx.20240412

摘要/Abstract

摘要：

早发性卵巢功能不全（premature ovarian insufficiency，POI）病因复杂，不仅会引起患者出现围绝经症状，还会影响女性生育率，损害女性身心健康。一旦卵巢功能受损便不可逆转。因此，探索POI的致病机制，延缓该病的发展至关重要。近年来研究者发现铁死亡与POI有着紧密关联。铁死亡是一种铁依赖性细胞死亡形式，可调控机体多种细胞生物过程。氧化应激、自噬、机体内铁代谢异常、脂质代谢异常都可能通过诱导铁死亡损害卵巢颗粒细胞以及卵泡，影响卵巢功能。同时Hippo/Yes相关蛋白（Yes-associated protein，YAP）、肿瘤蛋白p53（tumor protein p53，TP53）/核因子E2相关因子2（nuclear factor erythroid 2-related factor 2，Nrf2）信号通路的异常激活也可通过铁死亡损害卵巢功能。此外有研究发现谷胱甘肽过氧化物酶4（glutathione peroxidase 4，GPX4）、Fer-1（ferrostatin-1）、辅酶Q10（Coenzyme Q10，CoQ10）的活化可有效减轻铁死亡，可作为未来治疗POI的重要靶点。

关键词: 铁死亡, 原发性卵巢功能不全, 卵泡, 信号传导, 氧化性应激, 早发性卵巢功能不全

Abstract:

Premature ovarian insufficiency (POI) is a complex condition that not only leads to perimenopausal symptoms, but also affects female fertility and overall physical and mental health. Once ovarian function is impaired, it is irreversible. Therefore, exploring the pathogenic mechanisms of POI and delaying its progression are paramountly important. Recent studies have revealed a close relationship between ferroptosis and POI. Ferroptosis is an iron-dependent form of cell death that regulates a variety of cellular biological processes in the body. Oxidative stress, autophagy, abnormal iron metabolism, and lipid metabolism disorders can induce ferroptosis, damaging ovarian function. Additionally, abnormal activation of the Hippo/Yes-associated protein (YAP) and tumor protein p53 (TP53) / nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway can also impair ovarian function though ferroptosis. Moreover, research has found that activation of glutathione peroxidase 4 (GPX4), ferrostatin-1 (Fer-1), and Coenzyme Q10 (CoQ10) can effectively reduce ferroptosis, suggesting these as potential therapeutic targets for future treatment of POI.

Key words: Ferroptosis, Primary ovarian insufficiency, Ovarian follicle, Signal transduction, Oxidative stress, Premature ovarian insufficiency

高艺苇, 罗伟, 吴琼, 穆玉兰. 铁死亡与早发性卵巢功能不全的关系[J]. 国际妇产科学杂志, 2024, 51(5): 497-502.

GAO Yi-wei, LUO Wei, WU Qiong, MU Yu-lan. The Relationship Between Ferroptosis and Premature Ovarian Insufficiency[J]. Journal of International Obstetrics and Gynecology, 2024, 51(5): 497-502.

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