尿苷通过抑制小鼠的铁下垂来恢复卵母细胞质量并缓解雌性生殖衰老
Uridine restores oocyte quality and mitigates female reproductive aging by inhibition of ferroptosis in mice.
摘要(中文译文)
高龄是女性不孕的关键因素，主要源于卵巢储备和卵母细胞质量的下降。然而，生殖衰老背后的代谢机制仍不清楚。在此，我们发现与年轻对照组相比，老年小鼠血浆和卵巢中的尿苷水平显著降低。在此基础上，我们发现尿苷补充在体内和体外均能显著改善老年卵母细胞的减数分裂成熟、受精及早期胚胎发育。进一步的微小转录组分析揭示，尿苷通过抑制铁死亡和增强线粒体功能来提高卵母细胞质量。此外，通过整合有限蛋白水解-小分子映射、蛋白质印迹和基于siRNA的功能测定，我们鉴定出尿苷与poly(rC)结合蛋白1结合，从而抑制铁死亡并维持线粒体功能。总体而言，这些发现表明尿苷补充可改善老年雌性小鼠的生育力，并为卵母细胞衰老中的铁死亡提供了机制性见解。
Abstract
Advanced maternal age is a key factor in female infertility, primarily due to declines in ovarian reserve and oocyte quality. However, the metabolic mechanisms underlying reproductive aging remain unclear. Here, we show that uridine levels in the plasma and ovaries of aged mice are significantly reduced compared with young controls. Building on this, we find that uridine supplementation significantly improves meiotic maturation, fertilization, and early embryonic development of aged oocytes, both in vivo and in vitro. Further microtranscriptomic analyses reveal that uridine enhances oocyte quality by inhibiting ferroptosis and enhancing mitochondrial function. Moreover, by integrating Limited Proteolysis-Small Molecule Mapping, western blotting and siRNA-based functional assays, we identify that uridine binds to poly(rC)-binding protein 1, thereby suppressing ferroptosis and preserving mitochondrial function. Collectively, these findings demonstrate that uridine supplementation improves fertility in aged female mice and provide mechanistic insight into ferroptosis in oocyte aging.
如何引用
AMA
Jingyue Chen, Jianing Shen, Dongxu Li, Guangjun Huang, Rui Wang, Xiaofan Sun, et al. Uridine restores oocyte quality and mitigates female reproductive aging by inhibition of ferroptosis in mice.. Nature communications. 2026; doi:10.1038/s41467-026-72406-8.
APA
Jingyue Chen, Jianing Shen, Dongxu Li, Guangjun Huang, Rui Wang, Xiaofan Sun, et al (2026). Uridine restores oocyte quality and mitigates female reproductive aging by inhibition of ferroptosis in mice.. Nature communications. https://doi.org/10.1038/s41467-026-72406-8
GB/T 7714
Jingyue Chen, Jianing Shen, Dongxu Li, Guangjun Huang, Rui Wang, Xiaofan Sun, et al. Uridine restores oocyte quality and mitigates female reproductive aging by inhibition of ferroptosis in mice.[J]. Nature communications, 2026 doi:10.1038/s41467-026-72406-8.
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