Lactate metabolism and lactylation in female reproductive diseases: From metabolic rewiring to biomarkers and translational therapeutics

BACKGROUND: Lactate is increasingly recognized not only as a metabolic end product of glycolysis but also as a signaling metabolite that links metabolic reprogramming to epigenetic and transcriptional regulation through protein lactylation. Emerging evidence suggests that the lactate-lactylation axis contributes to the pathogenesis of female reproductive diseases, including endometriosis, endometrial cancer, polycystic ovary syndrome, and ovarian cancer. MAIN BODY: This review summarizes current evidence on lactate production, lactate transport, and histone/non-histone lactylation in female reproductive diseases. Available studies indicate that aberrant lactate accumulation and lactylation may influence chromatin accessibility, transcription factor activity, immune remodeling, ferroptosis resistance, steroidogenic dysfunction, and DNA damage repair. These processes may contribute to disease progression and may provide candidate biomarkers or therapeutic targets, including lactylation-related enzymes, lactate transporters, glycolytic regulators, and lactate-depleting strategies. However, the current evidence base remains dominated by cell and animal studies, and major barriers persist, including incomplete identification of bona fide reader proteins, insufficient standardization of site-specific lactylation detection, limited validation in human cohorts, and uncertainty regarding disease specificity. CONCLUSION: The lactate-lactylation axis provides a useful framework for understanding metabolic-epigenetic coupling in female reproductive diseases and may inform future biomarker development, patient stratification, and mechanism-based therapeutic strategies.