ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Pathology
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1626938
This article is part of the Research TopicGenomic Insights into Reproductive Regulation: Advances in Male and Female Fertility MechanismsView all 6 articles
Fibroblast growth factor 19 regulates the progression of polycystic ovary syndrome progression via FGFR4-ERK-NRF2 pathway
Provisionally accepted
- Shanghai First Maternity and Infant Hospital, Shanghai, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: FGF19, an endocrine hormone, participating in ovarian function. This study investigated the roles of FGF19 in polycystic ovary syndrome (PCOS) and its associated molecular mechanisms, specifically focusing on the FGFR4-ERK-NRF2 pathway. Methods: Clinical samples were collected to determine FGF19 levels, and proteomic analysis was performed on follicular fluid. A mouse model was established to investigate the molecular pathogenesis of PCOS. Subsequently, a series of in vitro experiments explored the effects and mechanisms of FGF19 on PCOS with and without oxidative stress. Results: Proteomics identified 144 differentially expressed proteins enriched in pathways including VEGF, PPAR, IL-2-STAT5, mTORC1, epithelial-mesenchymal transition, bile acid metabolism, and oxidative phosphorylation. FGF19/FGF15 levels were significantly higher in PCOS patients and mice compared to controls. In PCOS mice, FGFR4, NRF2, and HO1 were upregulated, while p-ERK/ERK levels were decreased. FGF19 overexpression promoted KGN cells viability while inhibiting apoptosis, upregulating FGFR4, NRF2, HO1, BCL2, and p-ERK/ERK, and downregulating BAX. However, LY3214996 reversed the action of FGF19 overexpression in KGN cells. H2O2 treatment decreased KGN cell viability, increased apoptosis, and elevated ROS levels. NRF2 knockdown further aggravated H2O2’s effectd, whereas FGF19 overexpression countered the changes in viability, apoptosis, and ROS levels caused by H2O2. Furthermore, H2O2 stimulation upregulated BAX, NRF2, and HO1, while decreasing BCL2 and p-ERK/ERK levels; NRF2 knockdown further upregulated BAX and downregulated BCL2 and p-ERK/ERK. Conversely, FGF19 overexpression had opposite effects on NRF2 knockdown. Conclusions: FGF19 may be involved in PCOS occurrence and development through the regulation of the FGFR4-ERK-NRF2 pathway.
Keywords: Polycystic Ovary Syndrome, ERK pathway, Nrf2, Oxidative Stress, FGF19
Received: 12 May 2025; Accepted: 15 Aug 2025.
Copyright: © 2025 Qu, Qiu, Wang, Chen, Miaoxin, Teng and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yiran Li, Shanghai First Maternity and Infant Hospital, Shanghai, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.