Heme metabolism and HO‐1 in the pathogenesis and potential intervention of endometriosis

Abstract Endometriosis (EM) is one of the diseases related to retrograded menstruation and hemoglobin. Heme, released from hemoglobin, is degraded by heme oxygenase‐1 (HO‐1). In EM lesions, heme metabolites regulate processes such as inflammation, redox balance, autophagy, dysmenorrhea, malignancy, and invasion, where macrophages (Mø) play a fundamental role in their interactions. Regulation occurs at molecular, cellular, and pathological levels. Numerous studies suggest that heme is an indispensable component in EM and may contribute to its pathogenesis. The regulatory role of heme in EM encompasses cytokines, signaling pathways, and kinases that mediate cellular responses to external stimuli. HO‐1, a catalytic enzyme in the catabolic phase of heme, mitigates heme's cytotoxicity in EM due to its antioxidant, anti‐inflammatory, and anti‐proliferative properties. Certain compounds may intervene in EM by targeting heme metabolism, guiding the development of appropriate treatments for all stages of endometriosis.