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Title: The impact of CXCL12 in BMDSCs endometrial trafficking, in endometrial receptivity molecules and in implantation rates in a mice model of endometriosis.

Grant number: 17/11469-0
Support type:Scholarships abroad - Research
Effective date (Start): September 01, 2017
Effective date (End): July 25, 2018
Field of knowledge:Health Sciences - Medicine - Maternal and Child Health
Principal Investigator:Ana Carolina Japur de Sá Rosa e Silva
Grantee:Ana Carolina Japur de Sá Rosa e Silva
Host: Hugh S Taylor
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Local de pesquisa : Yale School of Medicine (YSM), United States  

Abstract

Infertility secondary to endometriosis seems to be result of many factors associated to the reproductive process that are impaired in patients with this disease. Bone Marrow derived Stem Cell (BMDSCs) trafficking have been recently identified as a natural source of cells for the physiological regenerative process in the endometrium and in patients with endometriosis this function seem to be compromised, especially if active lesions are present. This project aims to investigate the impact of CXCL12, a stem cell chemotaxic substance, and of its antagonist (the ADM3100), in BMDSCs trafficking, in endometrial receptivity molecules and in implantation rates in a mice model of endometriosis. The study design proposes the use of a murine experimental model were animals submitted to bone marrow transplantation (BMT) with marked cells, in order to allow the identification of these cells during the migration process to the topic endometrium, will be also submitted to a laparotomy to induce endometriosis by endometrial implantation in the peritoneal wall or for sham procedure. After BMT and surgery for endometriosis induction (or not) all animals will receive (or not- control group) an intrauterine injection of CXCL12 and/or its antagonist, to evaluate the effect of this chemokine on BMDSCs trafficking, on the expression of endometrial receptivity biomarkers in the topic endometrium like: ±v² integrin, CD44, troponin and caderin-11. All these evaluations will be made by immunohistochemical analysis performed in the uterus (endometrium) three weeks after CXCL12 injection. Also, in order to evaluate the impact of CXCL12 on reproductive outcomes, instead of performing hysterectomy after 3 weeks of injection, the female mice in the study will be mated with male mice of proven fertility and checked daily for signs of pregnancy, during 30 days. When these female mice achieve pregnancy they will be set to sacrifice approximately one week later (ie, prior to delivery). Pregnancy rates, implantation rates, number and weight of the fetus will be the analyzed variables. (AU)