Wu Jiaqi, Zhao Xuehan, Fang Ying, Wang Cong, Tian Yichang, Tu Wan, Wu Qiqian, Yan Long, Yang Xiaokui
Department of Human Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China.
Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Cell Prolif. 2025 Mar 20:e70024. doi: 10.1111/cpr.70024.
Diminished ovarian reserve (DOR) is a pathological condition characterised by reduced ovarian function, which refers to the decreased quality and quantity of oocytes, potentially causing female infertility and various health issues. Follicular fluid (FF) serves as the microenvironment for follicular development and oocyte maturation, gaining an in-depth understanding of the metabolic state of FF will help us uncover the key biological processes involved in ovarian aging, while the specific underlying pathogenic mechanisms are not fully understood. In this study, we utilised pseudotargeted metabolomic analysis of FF to reveal the glycerophospholipid metabolism dysfunction mediated by GPD1L in DOR patients. We also found that GPD1L was downregulated in granulosa cells (GCs) of DOR patients, resulting in increased cell apoptosis and mitochondrial dysfunction. Moreover, our results demonstrated that the downregulated expression of GPD1L could induce follicular atresia and impair oocyte quality in mouse ovaries. Altogether, our research suggested that GPD1L in GCs and the key metabolites in the glycerophospholipid metabolism pathway could potentially act as novel biomarkers of DOR diagnosis, paving the way for a new theoretical basis for understanding the pathogenesis of DOR.
卵巢储备功能减退（DOR）是一种以卵巢功能降低为特征的病理状态，卵巢功能降低是指卵母细胞的质量和数量下降，这可能导致女性不孕及各种健康问题。卵泡液（FF）是卵泡发育和卵母细胞成熟的微环境，深入了解卵泡液的代谢状态将有助于我们揭示卵巢衰老所涉及的关键生物学过程，但其具体潜在致病机制尚未完全明确。在本研究中，我们利用卵泡液的伪靶向代谢组学分析揭示了DOR患者中由GPD1L介导的甘油磷脂代谢功能障碍。我们还发现DOR患者颗粒细胞（GCs）中GPD1L表达下调，导致细胞凋亡增加和线粒体功能障碍。此外，我们的结果表明GPD1L表达下调可诱导小鼠卵巢卵泡闭锁并损害卵母细胞质量。总之，我们的研究表明颗粒细胞中的GPD1L和甘油磷脂代谢途径中的关键代谢物可能作为DOR诊断的新型生物标志物，为理解DOR发病机制提供了新的理论基础。
