Ju Wenhan, Yan Binghan, Li Danping, Lian Fang, Xiang Shan
Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No. 1508 Yan'an West Road, Shanghai, 200052, China.
Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai, 201203, China.
J Transl Med. 2025 Sep 24;23(1):1005. doi: 10.1186/s12967-025-06966-6.
Ovarian ageing is a key factor in the decline of female fertility. It is primarily characterised by diminished oocyte quality, follicular depletion, and dysregulated hormone levels. In recent years, mitochondria-driven inflammation has emerged as a potential mechanism in ovarian ageing. Mitochondrial dysfunction results in the accumulation of reactive oxygen species (ROS) and the release of mitochondrial DNA (mtDNA), as well as the leakage of mitochondrial components and metabolites into the cytosol or extracellular space. These elements act as damage-associated molecular patterns (DAMPs), activating inflammasomes like NLRP3, thereby initiating and amplifying innate immune responses and contributing to sustained inflammation. Furthermore, an imbalance in mitochondrial quality control mechanisms can worsen the spread and persistence of inflammatory responses. In this study, we present a comprehensive overview of the signalling origins, molecular mechanisms of amplification, and key regulatory nodes involved in mitochondria-driven inflammation during ovarian ageing. Finally, we summarise potential therapeutic strategies targeting mitochondria-driven inflammation, offering novel perspectives and targets for delaying ovarian ageing and enhancing female reproductive health.
卵巢衰老乃是女性生育力下降的关键因素。其主要特征为卵母细胞质量下降、卵泡耗竭以及激素水平失调。近年来，线粒体驱动的炎症已成为卵巢衰老的一种潜在机制。线粒体功能障碍会导致活性氧（ROS）积累、线粒体DNA（mtDNA）释放，以及线粒体成分和代谢产物泄漏到细胞质或细胞外空间。这些成分作为损伤相关分子模式（DAMPs），激活NLRP3等炎性小体，从而启动并放大固有免疫反应，促成持续性炎症。此外，线粒体质量控制机制的失衡会加剧炎症反应的扩散和持续。在本研究中，我们全面概述了卵巢衰老过程中线粒体驱动的炎症的信号起源、放大的分子机制以及关键调控节点。最后，我们总结了针对线粒体驱动的炎症的潜在治疗策略，为延缓卵巢衰老和增进女性生殖健康提供了新的视角和靶点。
