Expresión tisular de los componentes del sistema fibrinolítico y de las metaloproteasas en la endometriosis.

Abstract

Endometriosis is defined by the presence of endometrial glands and stroma outside the uterus. It is a disease that affects up to 60% of women with pelvic pain and infertility. The etiology and pathogenesis of endometriosis are far from clear, despite several decades of research in this field. Although endometriosis is a benign disease, the endometrial tissue acquires the ability to attach and invade the peritoneum where a local extracellular proteolysis might take place. This process involves the plasminogen activator (PA) and matrix metalloproteinase (MMP) systems. The aim of this study is to analyse several components of the plasminogen activator (PA) pathway and the matrix metalloproteinase (MMP) system in endometriotic tissue, endometrium and peritoneal fluid from women with and without endometriosis (controls). 55 women with endometriosis and 37 controls were studied. In endometrium of women with endometriosis the antigenic levels of urokinase type-PA (uPA) and MMP-3 were elevated compared to endometrium from controls. Ovarian endometriotic tissues had higher antigenic levels of PA inhibitor type 1 (PAI-1) and MMP inhibitor type 1 (TIMP-1) than endometrium. The peritoneal fluid from women with endometriosis showed an increase in uPA levels. No differences were observed according to the presence of recurrence of the disease. Immunohystochemistry showed higher uPA expression in endometrium of women with endometriosis. PAI-1 was highly expressed in ovarian endometrioma stroma and endothelium. In situ hybridization showed an intense expression of PAI-1 mRNA in ovarian endometrioma. We conclude that the high levels of uPA and MMP-3 in endometrium of women with endometriosis might contribute to the invasive potential of endometrial cells. Once the ovarian endometriotic cyst is developed, high PAI-1 and TIMP-1 levels are detected and significant proteolytic activity is no longer observed. The increase of inhibitors and the reduction in proteolytic activity could explain the frequent clinical finding of isolated endometriotic cyst without invasion of the surrounding ovarian tissue.