Mitochondrial homeostasis: A key regulator in endometrial physiology and pathology.

Endometrial cyclic remodeling and decidualization are critical physiological processes for female reproductive function and are profoundly influenced by mitochondrial homeostasis. Mitochondrial homeostasis is maintained through the mitochondrial quality control system, which precisely regulates mitochondrial energy metabolism via peroxisome proliferator-activated receptor-gamma (PPARγ) coactivator-1 alpha (PGC-1α)-nuclear respiratory factor (NRF)1/2-mediated biogenesis, mitofusin (MFN)1/2-optic atrophy (OPA1)-dependent fusion, dynamin-related protein (DRP)1-regulated fission, and PTEN-induced putative kinase 1 (PINK1)-Parkin-executed mitophagy. Dysregulation of this system caused by infection, endocrine disruption, or iatrogenic injury can alter or reprogram endometrial energy metabolism, disrupt immune balance, and promote fibrosis and abnormal proliferation, leading to various endometrial diseases and impaired fertility. This review systematically summarizes recent research advances on mitochondrial homeostasis in endometrial physiology and pathology, and its emerging role as a therapeutic target, aiming to provide insights and references for therapeutic strategies against endometrial diseases.