Evaluation of the frequency of G-765C polymorphism in the promoter region of the COX2 gene and correlation with the expression of this gene in the endometrium of women with implantation failure with and without endometriosis

• Grant number: 12/03564-0
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2012
• End date: June 30, 2014
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Bianca Alves Vieira Bianco
• Grantee: Bianca Alves Vieira Bianco
• Host Institution: Faculdade de Medicina do ABC (FMABC). Organização Social de Saúde. Fundação do ABC. Santo André , SP, Brazil
• Associated researchers: Caio Parente Barbosa

Abstract

Among the main factors related to female infertility are endometriosis and embryo implantation failure. Endometriosis is a steroid-dependent condition in which tissue histologically similar to endometrium with glands and stroma grows outside the uterine cavity, causing pelvic pain and infertility. It is estimated that approximately 10-15% of women of reproductive period, about 40% of women with pelvic pain and 50% of women with fertility problems have this disease.Clinically, a major concern in relation to endometriosis is its propensity to cause infertility. The association between endometriosis and infertility is well established, but the mechanisms responsible for these effects are unknown.The endometrium undergoes changes during the female menstrual cycle that are critical for embryo implantation, which involves a complex interaction between the embryo and maternal endometrium, which occurs between the 20th and 24th day - window of implantation. In humans, the deployment process begins with the attachment of the embryo to epithelial endothelial and epithelial full intrusion then invasion and deciduous resulting in the stromal compartment of the anchoring property of the fetus and the placenta and fetal blood support. The complete molecular mechanism of embryo implantation is not known, but it is known that abnormalities in the endometrium results in implantation failure contributing to infertility found in most patients with endometriosis.In addition, recurrent miscarriage, low quality of oocytes and early embryonic loss has been observed in women with endometriosis. However, the exact etiology and pathogenesis of endometriosis are unclear, but genetic and environmental factors have been associated with the disease by several authors.Recently, COX2 enzyme (enzyme isoform Cycloxygenase 2) and prostaglandins have been associated with various pathological conditions of the reproductive tract, including carcinomas, menorrhagia, dysmenorrhea and endometriosis. The transcription of the COX2 gene (ID 4513) is rapidly activated by growth factors and oncogenes play important roles in inflammation and tumorigenesis. The importance of COX2 was observed in reproduction studies in knockout mice, where absence of the COX2 gene resulted in multiple reproductive failures including failures in ovulation, fertilization, implantation and decidualization confirming that prostaglandins produced by COX2 have an important role in this process.In vitro studies have also demonstrated that the synthesis of prostaglandins resulting from expression of the enzyme COX 2 can promote angiogenesis, cell proliferation, inhibit apoptosis, and promote the invasion of surrounding tissues. A polymorphism in the promoter region of the COX2 gene leads to an exchange of G (guanine) to C (cytosine) at position -765 of the gene (rs20417), causing a decrease in activity in vitro and consequently reducing the formation of prostaglandins.Salazar et al (2010) studied the G765C polymorphism of the COX2 gene in 106 Chilean women undergoing assisted reproduction techniques with implantation failure and 80 fertile controls. The results showed statistically significant differences in the distribution of genotypes and alleles between cases and controls, suggesting an important role of polymorphism in the failure of embryo implantation. In endometriosis There are no studies of the role of polymorphism and G765C COX2 gene disease. In order to try to clarify a possible mechanism that leads to infertility in women with endometriosis, we propose to study the G-765C polymorphism in the promoter region of the gene and correlates it COX2 gene expression in the endometrium of women with endometriosis fertile and infertile and compare the results with a group of women without endometriosis with failure of embryo implantation and a group of fertile women without endometriosis. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CAVALCANTI, VIVIANE; PONCE, TATIANA GUIDA; MAFRA, FERNANDA ABANI; ANDRE, GUSTAVO MENDONCA; CHRISTOFOLINI, DENISE MARIA; BARBOSA, CAIO PARENTE; BIANCO, BIANCA. Evaluation of the frequency of G-765C polymorphism in the promoter region of the COX-2 gene and its correlation with the expression of this gene in the endometrium of women with endometriosis. ARCHIVES OF GYNECOLOGY AND OBSTETRICS, v. 293, n. 1, p. 109-115, JAN 2016. (13/07978-6, 12/03564-0)