Current concepts of the pathogenesis of endometriosis
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REVIEW ARTICLE
Current concepts of the pathogenesis of endometriosis Yutaka Osuga
Received: 29 June 2009 / Accepted: 3 August 2009 / Published online: 26 August 2009 Ó Japan Society for Reproductive Medicine 2009
Abstract Endometriosis is a disease that causes the health of women of reproductive age to deteriorate. The implantation theory is the most widely accepted pathogenesis of the disease, although many points remain poorly understood concerning this theory. According to this theory, regurgitated endometrial debris has to go through various sequential events for the disease to develop. Recent studies have elucidated several aspects of these events. A remarkably reduced gene expression of GnRH II and an increase in uterine contraction-induced IL-8 secretion are suggested to be pathogenic changes in the eutopic endometrium of women with endometriosis. An increased level of osteoprotegerin in the peritoneal fluid of women with endometriosis is suggested to impede tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of endometriotic cells. An increase in the concentration of hepatocyte growth factor and a decrease in the concentration of interferon gamma-inducible protein-10 in the peritoneal fluid of women with endometriosis may stimulate the angiogenesis and development of endometriosis. Midkine, the concentration of which is very high in the follicular fluid of the ovary, may stimulate the growth of endometriosis at the time of ovulation. Immune cells, such as macrophages, lymphocytes, mast cells, and neutrophils, in endometriotic lesions are suggested to play important roles in the progression of the disease. For example, IL-4 from Th2 cells, IL-17 from Th17 cells, tryptase from mast cells, and some serine proteases from
Y. Osuga (&) Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan e-mail: [email protected]
neutrophils have been shown to stimulate endometriotic stromal cells, suggesting their specific roles in endometriosis. Interestingly, adiponectin, a key factor in metabolism, also appears to be involved in the pathogenesis of endometriosis. These novel findings sustain the current understanding of the pathogenesis of endometriosis. Keywords Cytokine Endometriosis Immune cell Pathogenesis Uterine contraction
Introduction Endometriosis, the presence of endometrium-like glands and stroma outside the uterus, is a common, poorly understood, and extremely debilitating benign gynecological condition. It affects mainly women of reproductive age, causing pelvic pain and infertility. In addition, malignancies, though not common, can arise from the endometriotic lesion of the ovary. Currently, no cure exists for the disease, and treatment is directed to medical suppression, surgical excision, and alleviation of symptoms. The etiology and pathophysiology of endometriosis are not well understood. Classically, three theories exist to explain the etiology of endometriosis. The implantation
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