Antifibrotic drug finerenone restores fertility in premature ovarian insufficiency

• 成果类型: Article
• 署名作者: Lin, Zexiong; Li, Yuan; Zhao, Yu; Liu, Dongteng; Deng, Shuzi; Gu, Jingkai; Li, Yanyan; Zhao, Xudong; Wu, Peishan; Xiao, Yuan; Su, Jiaping; Sun, Yiting; Zhang, Yihui; Lee, Yin Lau; Sato, Yorino; Zeng, Haitao; Lu, Haonan; Zhang, Juanhui; Ko, Jennifer K. Y.; Zhao, Jing; Kawamura, Kazuhiro; Ng, Ernest H. Y.; Jiang, Shanfang; Li, Yu; Xia, Xi; Chan, Karen K. L.; Yeung, William S. B.; Wang, Tianren R.; Liu, Kui
• 署名单位: University of Hong Kong; University of Hong Kong; Juntendo University; Sun Yat Sen University; Peking University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.adz4075
• 发表日期: 2026-02-05
• 页码: eadz4075
• 关键词: FOLLICLE ACTIVATION

摘要

Currently, no effective treatment exists for infertility associated with premature ovarian insufficiency (POI) because affected patients lack hormone-responsive antral follicles. By screening a Food and Drug Administration (FDA)-approved drug library, we identified finerenone, a kidney disease medication, as a promising drug for restoring fertility in POI. Finerenone stimulated follicle development in aged mice and restored antral follicle development in patients with POI following oral administration, resulting in mature oocytes and embryos. Mechanistically, finerenone reduced fibrotic deposition in the ovarian stroma, alleviating collagen-mediated suppression of follicular development. Building on this insight, we identified additional FDA-approved oral antifibrotic drugs as potential treatments for POI-related infertility. Our findings highlight the ovarian stroma-rather than the follicles themselves-as the key therapeutic target and offer potential therapeutic leads for POI-related infertility.