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Antifibrotic drug finerenone restores fertility in premature ovarian insufficiency

Science. 2026-02; 
Zexiong Lin, Yuan Li, Yu Zhao, Dongteng Liu, Shuzi Deng, Jingkai Gu, Yanyan Li, Xudong Zhao, Peishan Wu, Yuan Xiao, Jiaping Su, Yiting Sun, Yihui Zhang, Yin Lau Lee, Yorino Sato, Haitao Zeng, Haonan Lu, Juanhui Zhang, Jennifer K Y Ko, Jing Zhao, Kazuhiro Kawamura, Ernest H Y Ng, Shanfang Jiang, Yu Li, Xi Xia, Karen K L Chan, William S B Yeung, Tianren R Wang, Kui Liu
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Custom DNA/RNA Oligos For Col1a1 knock down, LNP- Col1a1- siRNA (150 nM; GenScript) and LNP- Control- siRNA (150 nM; GenScript) were used in the ovarian culture. For siRNA-mediated knockdown, cells were transfected with either a control siRNA (50 nM) or Nr3c2- targeting siRNA (50 nM; GenScript, sense: CCA UGC AUG AUU UGG UGA AdTdT; antisense: UUC ACC AAA UCA UGC AUG GdTdT). LNPs were prepared by GenScript (Nanjing, China). For Col1a1 gene silencing , a siRNA sequence targeting mouse Col1a1 mRNA (sense: CCU AUG GCU AUG AUG AAA AUU; antisense: UUU UCA UCA UAG CCA UAG GAC) was synthesized by GenScript. The control siRNAs were designed by the create- scrambled- sequence tool on Genscript’s website (https://www.genscript.com/tools/create-scrambled- sequence). Get A Quote

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 insigh... More

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