Histone lactylation: a novel epigenetic bridge linking cellular metabolism to benign and malignant gynecological diseases

Lactic acid modification of histones represents an emerging post-translational modification that establishes a critical link between cellular metabolic reprogramming and epigenetic regulation through the covalent binding of lactic acid to histone lysine residues. In recent years, the mechanisms underlying this modification in the pathogenesis of various diseases have been progressively elucidated, revealing its extensive biological impact and potential clinical translational value. As research progresses, the functional role of histone lactylation in gynecological diseases has become increasingly evident, offering a novel epigenetic perspective for deciphering the pathogenesis of gynecological-related disorders. This review outlines the mechanisms underlying histone lactylation and focuses on its regulatory role in common benign and malignant gynecological diseases. The malignant diseases discussed include ovarian, endometrial, and cervical cancers, while the benign conditions include endometriosis and polycystic ovary syndrome. Furthermore, it undertakes an analysis of the therapeutic potential of histone lactylation modifications and reviews emerging targeted therapeutic strategies. These include targeting lactate production, lactate transport, lactylation-associated enzymes, or downstream effectors, highlighting their potential to intervene in disease progression. The present study aims to systematically elucidate the core value of histone lactylation as a novel epigenetic link between metabolism and gynecological disease pathogenesis. In addition, it provides clear research directions and robust theoretical support for developing targeted therapeutic strategies based on lactylation modifications. Similar content being viewed by others Abbreviations - PTMs: - Post-translational modifications - HDAC: - Histone deacetylases - TME: - Tumor microenvironment - ACSS2: - Acyl-CoA synthetase short-chain family member 2 - HATs: - Histone acetyltransferases - CBP: - CREB-binding protein - EMS: - Endometriosis - PCOS: - Polycystic ovary syndrome - OC: - Ovarian cancer - EOC: - Epithelial ovarian cancer - LDHB: - Lactate Dehydrogenase B - PD-L1: - Programmed death-ligand 1 - PD-1: - Programmed death-1 - HGSOC: - High-grade serous ovarian carcinoma - HR: - Homologous Recombination - SEs: - Super-enhancers - 2-DG: - 2-deoxy-D-glucose - TCM: - Traditional Chinese medicine - CC: - Cervical Cancer - LDHA: - Lactate dehydrogenase A - EC: - Endometrial Cancer - USP39: - Ubiquitin-specific protease 39 - PGK1: - Phosphoglycerate kinase 1 - NHE7: - Sodium-hydrogen exchanger 7 - DNMT1: - DNA methyltransferase 1 - HMGB1: - High mobility group protein 1 - lncRNA: - Long non-coding RNA - RASD2: - Ras-related dexamethasone-induced 2 - CTPS1: - Cytidine triphosphate synthase 1 - METTL3: - Methyltransferase-like 3 - PDAC: - Pancreatic ductal adenocarcinoma - HK: - Hexokinase - PK: - Pyruvate kinase - MCTs: - Monocarboxylate transporters - CTCF: - CCCTC-binding factor - BC: - Breast cancer

We acknowledge MedPeer (www.medpeer.cn) for providing the image materials for this entire paper. Funding This study was supported by the following grants: 1. National Natural Science Foundation of China (Grant No. 8257156377): Mechanism study of effective components of Lichong Sheng Sui Decoction in regulating oxidative stress-driven cold-hot transformation of ovarian cancer immune microenvironment based on multi-scale modeling. 2. Traditional Chinese Medicine Evidence-Based Capacity Improvement Project (Grant No. 202324): Evidence-based study on traditional Chinese medicine in the treatment of dominant disease “Zhengjia” (ovarian endometriotic cyst). Author information Authors and Affiliations Corresponding authors Ethics declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. About this article Cite this article You, W., Wang, S., Zhang, Y. et al. Histone lactylation: a novel epigenetic bridge linking cellular metabolism to benign and malignant gynecological diseases. Clin Epigenet (2026). https://doi.org/10.1186/s13148-026-02185-y Received: Accepted: Published: DOI: https://doi.org/10.1186/s13148-026-02185-y