在小鼠卵细胞成熟过程中,FSP1调节铁和线粒体功能
Hongzhen Ruan1, Huifen Xiang1, Yajing Liu1
1Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei, 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No.81 Meishan Road, Hefei, 230032, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, No.81 Meishan Road, Hefei, 230032, China.
Experimental cell research
|March 20, 2025
概括
铁灭菌抑制蛋白1 (FSP1) 对卵细胞质量和介质成熟至关重要. 抑制FSP1会触发铁亡,导致介质衰竭和卵细胞发育受损.
科学领域:
- 生殖生物学 生殖生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 卵细胞质量对于成功受精和胚胎发育至关重要.
- 新出现的证据表明,受调节的细胞死亡 (ferroptosis) 对卵细胞质量产生负面影响.
- 铁灭菌抑制蛋白1 (FSP1) 在卵细胞中介成熟中的作用在很大程度上仍未被描述.
研究的目的:
- 研究FSP1在调节小鼠卵细胞中介成熟中的功能.
- 为了确定FSP1,ferroptosis和卵细胞质量之间的机械联系.
- 评估FSP1抑制对卵细胞发育和介质进展的影响.
主要方法:
- 在小鼠的卵细胞中性成熟过程中对FSP1表达的分析.
- 在卵细胞中药理上抑制FSP1.
- 评估介质性进展,线索完整性和染色体对齐.
- 测量细胞内铁含量,活性氧物种和脂质过氧化.
- 评估与铁亡相关的基因表达和线粒体功能.
主要成果:
- 在整个介质成熟期的小鼠卵细胞中检测到FSP1表达,在老年小鼠中减少.
- 抑制FSP1干扰了介质性进展,导致形缺陷,染色体不对齐和介质性停止.
- 抑制FSP1诱导的铁亡,由细胞内铁的增加,活性氧物种,脂质过氧化和基因表达的改变证明.
- 在FSP1抑制后观察到线粒体功能障碍,包括异常分布和受损的ATP产生.
结论:
- FSP1是卵细胞中介成熟的关键调节者,对于维持铁的稳态和线粒体功能至关重要.
- 抑制FSP1会触发铁亡,导致卵细胞介质失败和质量受损.
- 这些发现凸显了FSP1作为在生殖医学中改善卵细胞质量的潜在治疗点.
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