Research progress on protein lactylation in female reproductive disease: molecular mechanisms, functions, and therapeutic implications.

Female reproductive health depends on precisely coordinated metabolic, hormonal, immune, and epigenetic networks. Lactylation is a lactate-derived lysine post-translational modification that provides a direct mechanism by which glycolytic metabolism influences chromatin activity and protein function. Lactylation exerts diverse biological effects across multiple systems, including the cardiovascular, musculoskeletal, nervous, and urinary systems. Although individual studies have indicated that lactylation participates in key reproductive processes and contributes to various female reproductive disorders, the mechanisms connecting lactylation with female reproductive health and disease have not been systematically reviewed. Thus, we provide an integrated overview of lactylation-associated cellular mechanisms and the research progress in female reproductive health and disease. This review examines the molecular mechanisms of lactylation and its interactions with other post-translational modifications. We further summarize the physiological and pathological functions of lactylation in the female reproductive system, with particular emphasis on its context-dependent and double-edged role. We also outline emerging therapeutic strategies targeting lactate production, transport, lactylation enzymes, specific lactylation sites, together with clinical trials, while emphasizing key challenges associated with tissue specificity, reproductive safety, and precise modulation. This review highlights lactylation as a metabolic-epigenetic regulator and a potential therapeutic target for precision management of female reproductive diseases.