{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:05:45Z","timestamp":1790960745705,"version":"4.1.0"},"reference-count":191,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health (NIH) RO1","award":["HD106285"],"award-info":[{"award-number":["HD106285"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cells"],"abstract":"<jats:p>Chemical modifications of RNA add a dynamic regulatory layer to gene expression beyond the genome and epigenome. Among these modifications, 5-methylcytidine (m5C) has emerged as a key epitranscriptomic modification that influences RNA stability, translation, localization, and stress responses across diverse biological systems. Recent advances in high-resolution mapping and functional interrogation of m5C have revealed its involvement in development, metabolism, immune regulation, and disease pathogenesis. Notably, many of these processes are highly relevant to women\u2019s health, which is shaped by hormone-responsive tissues, reproductive transitions, and pregnancy-associated physiological adaptations. In this review, we provide a comprehensive and integrative overview of m5C RNA modification with a focus on its roles in female biology and disease. We summarize the molecular machinery responsible for m5C deposition, recognition, and regulation, as well as current detection technologies. We further highlight emerging evidence linking m5C dysregulation to early embryonic development, women-specific cancers, gynecologic and reproductive disorders, pregnancy complications, and metabolic and cardiovascular diseases. In addition, we discuss the interplay between m5C and sex hormone signaling, as well as the potential of m5C as a biomarker and therapeutic target. Finally, we identify key knowledge gaps, including the need for tissue-specific, longitudinal, single-cell, and spatial epitranscriptomic studies in women. By integrating epitranscriptomics into women\u2019s health research, this review underscores m5C as a previously underappreciated regulatory layer with significant implications for precision medicine and clinical translation.<\/jats:p>","DOI":"10.3390\/cells15090847","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T12:15:07Z","timestamp":1778156107000},"page":"847","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["5-Methylcytidine RNA Epitranscriptomics in Women\u2019s Health and Disease: Mechanisms and Clinical Implications"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7131-8946","authenticated-orcid":false,"given":"Qiwei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5736-0424","authenticated-orcid":false,"given":"Sana M.","family":"Salih","sequence":"additional","affiliation":[{"name":"Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongxue","family":"Wu","sequence":"additional","affiliation":[{"name":"Section of Cardiology, Department of Medicine, Biological Sciences Division, University of Chicago, Chicago, IL 60637, USA"},{"name":"Division of Cardiac Surgery, Department of Surgery, Dorothy M. Davis Heart & Lung Research Institute, Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itika","family":"Arora","sequence":"additional","affiliation":[{"name":"Department of Public Health and Epidemiology, Khalifa University, Abu Dhabi P.O. Box 127788, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5676-3221","authenticated-orcid":false,"given":"Mira","family":"Mousa","sequence":"additional","affiliation":[{"name":"Department of Public Health and Epidemiology, Khalifa University, Abu Dhabi P.O. Box 127788, United Arab Emirates"},{"name":"Center for Biotechnology, Khalifa University, Abu Dhabi P.O. Box 127788, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8778-4447","authenticated-orcid":false,"given":"Ayman","family":"Al-Hendy","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL 60637, USA"},{"name":"Center for Biotechnology, Khalifa University, Abu Dhabi P.O. Box 127788, United Arab Emirates"},{"name":"Department of Medical Sciences, Khalifa University, Abu Dhabi P.O. Box 127788, United Arab Emirates"},{"name":"Department of Obstetrics and Gynecology, Sheik Shakhbout Medical City, Abu Dhabi P.O. Box 127788, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Boyer","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2007.02.005","article-title":"Chromatin modifications and their function","volume":"128","author":"Kouzarides","year":"2007","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/s41580-019-0159-6","article-title":"The diverse roles of DNA methylation in mammalian development and disease","volume":"20","author":"Greenberg","year":"2019","journal-title":"Nat. Rev. Mol. 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