5-Methylcytidine RNA Epitranscriptomics in Women's Health and Disease: Mechanisms and Clinical Implications

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's 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's health research, this review underscores m⁵C as a previously underappreciated regulatory layer with significant implications for precision medicine and clinical translation.