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Evaluation of the ezrin and the ezrin phosphorylated protein expression in lesions of pelvic endometriosis

Grant number: 13/03997-6
Support type:Research Grants - Visiting Researcher Grant - International
Duration: May 28, 2013 - June 05, 2013
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Maurício Simões Abrão
Grantee:Maurício Simões Abrão
Visiting researcher: Frederick Naftolin
Visiting researcher institution: New York University, United States
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:10/10338-0 - Endometriosis: molecular bases of immune response, AP.TEM

Abstract

I. Evaluation of Ezrin and phosphorylated Ezrin protein expression in lesions of pelvic endometriosisa) The expression of the Ezrin and phosphorylated Ezrin protein will be assessed by immunohistochemistry in samples of topic endometrium topic and pelvic endometriosis (peritoneal, ovarian and bowel) from patients with endometriosis and endometrial samples from patients without the disease (controls).b) In patients with endometriosis, the expression of Ezrin and Ezrin phosphorylated will be correlated with symptoms, menstrual cycle phase, staging and histological classification of endometriosis. c) In relation to the control patients (without endometriosis), the expression of Ezrin and Ezrin phosphorylated will be correlated with the phase of the menstrual cycle and symptoms. All results obtained in items (b) and (c) will be compared between patients with and without endometriosis. II. Activity of teaching for researchers and post-graduate students1. Ezrin, a structural protein of the cytoskeleton in normal endometrium and endometriosis2. Possible functions of Ezrin in epithelial-mesenchymal transition (EMT)3. The expression of Polysialylated Neural Cell Adhesion Factor (PSA-NCAM) blocks the adhesion of monocytes to endothelium of human coronary artery treated with hormone4. Synaptic plasticity induced by estrogen and gonadotropin peak in the middle of ovarian cycle.5. KRONOS: Study of Early Estrogen Prevention (KEEPS)III. Discussion of the future project in collaboration Epithelial-mesenchymal transformation (EMT) of the peritoneum by the endometrium. Endometriosis is a common and serious cause of infertility, pelvic pain and surgery in women. The pathogenesis of endometriosis is still largely unknown. The most widely accepted mechanism for the development of endometriosis is based on the hypothesis of Samson, which consists in the implantation of endometrial cells, derived from the reflux of menstrual blood in the abdominal and peritoneal cavity. In this project, we propose that this penetration into the peritoneum requires the EMT process of peritoneal cells and adjusting junctional connections, thereby allowing the passage of endometrial cells. This study will evaluate the role of Ezrin protein expression in the EMT, and some of the mechanisms by which EMT is regulated using an in vivo model of endometriosis in rats, where the endometrial surface of a horn of the uterus in diestrus stage will be fixed at the back the fornix. After two weeks, the rats will be sacrificed and tissues will be analysed: a) characterization of the morphology by hematoxylin-eosin and Masson tri-chrome staining, which will allow the visualization of the endometriotic lesions and adhesions, thereby enabling the assessment of the morphology of peritoneal cells. b) analysis of Ezrin protein, by immunohistochemistry using monoclonal antibodies specific for both forms of the protein: Ezrin and Ezrin phosphorylated and MAC-1, followed diamino-benzidine, thereby allowing the evaluation of the location and intensity of the expression of Ezrin, Ezrin phosphorylated and macrophages, respectively. (AU)