{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T01:07:46Z","timestamp":1788052066653,"version":"build-2784847793"},"reference-count":109,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HD094380"],"award-info":[{"award-number":["R01HD094380"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HD111243"],"award-info":[{"award-number":["R01HD111243"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Uterine leiomyomas or fibroids are a common but pernicious benign tumor impacting between 70\u201380% of women of reproductive age. Despite their high prevalence, the etiology of uterine fibroids is not fully understood. This review aims to highlight the distinct metabolic features that uterine fibroids adopt to meet biosynthetic demands, support proliferation, extracellular matrix production, survival, and fibrosis. Specifically, we posit the role of glycolytic reprogramming\u2014an adaptation in fibrosis across organs (lung, kidney, heart, and liver) as a major contributor to uterine fibroid development. Previous genetic, transcriptomic, proteomic, and metabolic studies have drawn strong links between metabolism and uterine fibroid biology and identified genotype-specific metabolic alterations such as fumarate hydratase (FH) deficiency and mediator of RNA polymerase II transcription (MED12) gene mutations. Studies in non-uterine models have linked glycolysis to ECM production and fibrosis through activation of transforming growth factor-beta (TGF-\u03b2) and the canonical Wnt pathway (Wnt\/\u03b2-catenin) signaling, supporting them as potential key pathways in uterine fibroid pathogenesis via glycolytic reprogramming. Other metabolic regulators, such as hypoxia-inducible factor 1-alpha (HIF-1\u03b1), mammalian target of rapamycin (mTOR), and phosphoinositide 3-kinase\/protein kinase B (PI3K\/Akt), may also sustain the fibrotic phenotype through coupling signaling that drives ECM production to metabolic programming. Overall, the proposed metabolic perspective of uterine fibroid pathogenesis invites further exploration of mechanistic investigation in uterine-specific models and therapeutic targeting through larger cohort studies.<\/jats:p>","DOI":"10.3390\/genes16111268","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T09:16:07Z","timestamp":1761642967000},"page":"1268","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Glycolytic Reprogramming in Uterine Fibroids: Genetic, Transcriptomic, Proteomic, and Metabolomic Insights"],"prefix":"10.3390","volume":"16","author":[{"given":"Samya","family":"El Sayed","sequence":"first","affiliation":[{"name":"Division of Reproductive Sciences and Women\u2019s Health Research, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvina","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1164-5774","authenticated-orcid":false,"given":"Valentina","family":"Vanos","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4591-8168","authenticated-orcid":false,"given":"Rachel","family":"Michel","sequence":"additional","affiliation":[{"name":"Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0554-132X","authenticated-orcid":false,"given":"Mostafa","family":"Borahay","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.5114\/aoms\/171786","article-title":"Global Epidemiological Characteristics of Uterine Fibroids","volume":"19","author":"Li","year":"2023","journal-title":"Arch. 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