Abstract
BackgroundEndometriosis is a common disease characterized by the presence of a functional endometrium outside the uterine cavity, causing pelvic pain, dysmenorrheal, and infertility. This disease has been associated to development of different types of malignancies; therefore new blood vessels are essential for the survival of the endometrial implant. Our previous observations on humans showed that angiogenesis is predominantly found in rectosigmoid endometriosis, a deeply infiltrating disease. In this study, we have established the experimental model of rat peritoneal endometriosis to evaluate the process of angiogenesis and to compare with eutopic endometrium.MethodsWe have investigated the morphological characteristics of these lesions and the vascular density, VEGF and its receptor Flk-1 and MMP-9 expression, and activated macrophage distribution, using immunohistochemistry and RT-PCR.ResultsAs expected, the auto-transplantation of endometrium pieces into the peritoneal cavity is a well-established method for endometriosis induction in rats. The lesions were cystic and vascularized, and demonstrated histological hallmarks of human pathology, such as endometrial glands and stroma. The vascular density and the presence of VEGF and Flk-1 and MMP-9 were significantly higher in endometriotic lesions than in eutopic endometrium, and confirmed the angiogenic potential of these lesions. We also observed an increase in the number of activated macrophages (ED-1 positive cells) in the endometriotic lesions, showing a positive correlation with VEGF.ConclusionThe present endometriosis model would be useful for investigation of the mechanisms of angiogenesis process involved in the peritoneal attachment of endometrial cells, as well as of the effects of therapeutic drugs, particularly with antiangiogenic activity.
Highlights
Endometriosis is a common disease characterized by the presence of a functional endometrium outside the uterine cavity, causing pelvic pain, dysmenorrheal, and infertility
We showed that the vascular density and the expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 (Flk-1) are significantly higher in deeply infiltrating endometriosis affecting the ovary, bladder and mainly the rectosigmoid, compared with the eutopic endometrium [16]
Morphological characterization of rat peritoneal endometriosis Endometriosis was induced by transplanting endometrial tissue to the rat peritoneal wall
Summary
Endometriosis is a common disease characterized by the presence of a functional endometrium outside the uterine cavity, causing pelvic pain, dysmenorrheal, and infertility This disease has been associated to development of different types of malignancies; new blood vessels are essential for the survival of the endometrial implant. Chen et al (2004) [10] reported higher metalloproteinase-9 (MMP-9) and lower tissue inhibitor of MMPs-1 (TIMP-1) immunostaining in ectopic and eutopic endometrium This enables the endothelial cells to migrate into the surrounding interstitium, resulting in the formation of capillary buds and sprouts [10]. The new vessel wall is stabilized by the attachment of mural cells, including pericytes and smooth muscle cells and the production of extracellular matrix compounds [11]
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