{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T14:17:24Z","timestamp":1790000244518,"version":"4.0.1"},"reference-count":117,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007847","name":"Natural Science Foundation of Jilin Province","doi-asserted-by":"publisher","award":["YDZJ202301ZYTS138"],"award-info":[{"award-number":["YDZJ202301ZYTS138"]}],"id":[{"id":"10.13039\/100007847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007847","name":"Natural Science Foundation of Jilin Province","doi-asserted-by":"publisher","award":["YDZJ202401147ZYTS"],"award-info":[{"award-number":["YDZJ202401147ZYTS"]}],"id":[{"id":"10.13039\/100007847","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Health Science and Technology Ability Improvement Program of Jilin Province","award":["2022JC048"],"award-info":[{"award-number":["2022JC048"]}]},{"name":"Health Science and Technology Ability Improvement Program of Jilin Province","award":["2024A082"],"award-info":[{"award-number":["2024A082"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Stress urinary incontinence (SUI) has long been understood as a structural failure of pelvic floor support. While this view explains acute anatomical damage, it offers little insight into why functionally similar injuries produce markedly different long-term outcomes, or why sphincteric deterioration often progresses years after the initial insult. In this review, we examine the possibility that progressive external urethral sphincter (EUS) degeneration reflects an underlying metabolic vulnerability. The EUS is a striated muscle of unusual metabolic demand, sustaining continuous basal tone through oxidative phosphorylation while retaining rapid contractile capacity. Its membranes are enriched in polyunsaturated fatty acids and subjected to recurrent ischemia\u2013reperfusion, features that are hypothesized to limit redox buffering capacity. We discuss how parturition trauma, aging, obesity, and neurogenic injury may converge to disrupt iron homeostasis, impair the GSH\/GPX4 antioxidant axis, and exhaust satellite cell-mediated repair. Crucially, direct evidence for ferroptosis in the EUS remains limited. We therefore integrate EUS-specific findings with evidence from skeletal muscle and other tissues to propose a hypothesis-generating framework. Rather than treating ferroptosis-associated stress as an isolated cell death pathway, we consider it a candidate biochemical nexus linking metabolic stress to fibro-adipogenic niche remodeling. By shifting focus from mechanical injury to eroding tissue resilience, this framework generates testable hypotheses regarding biomarker development and potential therapies aimed at restoring the adaptive capacity of the EUS.<\/jats:p>","DOI":"10.3390\/biom16091376","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:50:03Z","timestamp":1789995003000},"page":"1376","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Vulnerability and Regenerative Failure of the External Urethral Sphincter: A Ferroptosis-Associated Framework for Stress Urinary Incontinence"],"prefix":"10.3390","volume":"16","author":[{"given":"Shuo","family":"Sun","sequence":"first","affiliation":[{"name":"Changchun University of Chinese Medicine, Changchun 130117, China"},{"name":"The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Changchun University of Chinese Medicine, Changchun 130117, China"},{"name":"The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Pan","sequence":"additional","affiliation":[{"name":"Changchun University of Chinese Medicine, Changchun 130117, China"},{"name":"The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Yang","sequence":"additional","affiliation":[{"name":"Changchun University of Chinese Medicine, Changchun 130117, China"},{"name":"The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhitao","family":"Wei","sequence":"additional","affiliation":[{"name":"Changchun University of Chinese Medicine, Changchun 130117, China"},{"name":"The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3272","DOI":"10.1016\/j.scib.2024.04.074","article-title":"Female urinary incontinence in China after 15 years\u2019 efforts: Results from large-scale nationwide surveys","volume":"69","author":"Zhu","year":"2024","journal-title":"Sci. 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