Metabolic remodeling of endometriosis microenvironment: Energy stress and immune evasion

Endometriosis (EMs) is an estrogen-dependent chronic inflammatory gynecological disease characterized by ectopic growth of endometrial tissues, leading to dysmenorrhea, pelvic pain, and infertility. Although the retrograde menstruation theory clarifies the dissemination of endometrial fragments to ectopic sites, the mechanisms behind the survival of ectopic lesions and their immune evasion in hostile microenvironments remain unclear. Endometrial stromal cells (ESCs) are chronically exposed to a microenvironment of hypoxia, nutrient deprivation and oxidative stress, and this energy stress state drives the ESCs to develop adaptive metabolic reprogramming. Through remodeling glucose, lipid, and amino acid metabolic pathways, ESCs not only fulfill their own proliferative requirements but also utilize metabolites as signaling mediators to modulate immune cell functions. This review elaborates on the characteristics of energy stress-driven metabolic reprogramming in EMs, deciphers its mechanisms underlying immune evasion, and discusses the therapeutic potential of combined metabolic-immune intervention strategies.