Potential involvement of iron in the pathogenesis of peritoneal endometriosis

Abstract

The aim of this study is to review the current literature associating endometriosis with iron and to discuss the potential causes and consequences of iron overload in the pelvic cavity. Indeed, iron is essential for all living organisms. However, excess iron can result in toxicity and is associated with pathological disorders. In endometriosis patients, iron overload has been demonstrated in the different components of the peritoneal cavity (peritoneal fluid, endometriotic lesions, peritoneum and macrophages). Animal models allow us to gather essential information on the origin, metabolism and effect of iron overload in endometriosis, which may originate from erythrocytes carried into the pelvic cavity mainly by retrograde menstruation. Peritoneal macrophages play an important role in the degradation of these erythrocytes and in subsequent peritoneal iron metabolism. Iron overload could affect a wide range of mechanisms involved in endometriosis development, such as oxidative stress or lesion proliferation. In conclusion, excess iron accumulation can result in toxicity and may be one of the factors contributing to the development of endometriosis. Treatment with an iron chelator could thus be beneficial in endometriosis patients to prevent iron overload in the pelvic cavity, thereby diminishing its deleterious effect.

Macrophages Are Alternatively Activated in Patients with Endometriosis and Required for Growth and Vascularization of Lesions in a Mouse Model of Disease

“…35,36 Aging erythrocytes, accumulating and dying into the pelvic cavity because of retrograde menstruation, cause iron overload. 37 Iron overload is greater in peritoneal macrophages, which are in charge of erythrocytes phagocytic clearance. 20,38 Iron overload could as well influence macrophage activation.…”

Hypoxia regulates the ferrous iron uptake and reactive oxygen species level via divalent metal transporter 1 (DMT1) Exon1B by hypoxia‐inducible factor‐1

“…However, continued delivery of iron to cells can overwhelm the capacity of ferritin to store and sequester the metal, inducing oxidative injury to cells. Indeed, iron can act as a catalyst in the Fenton reaction to potentiate oxygen and nitrogen toxicity by the generation of a wide range of free radical species, including hydroxyl radicals, or the peroxynitrite anion, produced by the reaction between NO and the superoxide anion (22). Hydroxyl radicals are the most reactive free radical species known and have the ability to react with a wide range of cellular constituents, including aminoacid residues and purine and pyrimidine bases of DNA, as well as attacking membrane lipids to initiate a free radical chain reaction known as lipid peroxidation (22).…”

Role of iron overload-induced macrophage apoptosis in the pathogenesis of peritoneal endometriosis

“…The presence of iron overload has been demonstrated in various components of the peritoneal cavity of endometriosis patients (peritoneal fluid, macrophages, and endometriotic lesions; Defrere et al 2008, Augoulea et al 2012, which strongly suggests disruption of iron homeostasis in the peritoneal cavity of patients. Iron overload in the peritoneal fluid provokes oxidative injury and inflammatory response, involving peritoneal macrophages in particular, which promote the proliferative capacity of ectopic implants of endometrium in the peritoneal cavity (Van Langendonckt et al 2002b, Szczepariska et al 2003.…”