Effects of isoflavones and 17 beta-estradiol on the uterine extracellular matrix of diabetic rats: relevance to hormone therapy

• Grant number: 15/03569-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: May 15, 2015
• End date: May 14, 2016
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Manuel de Jesus Simões
• Grantee: Adriana Aparecida Carbonel Castro Ferreira
• Supervisor: Benjamin K. Tsang
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: University of Ottawa (uOttawa), Canada
• Associated to the scholarship: 14/17077-9 - Effects of isoflavones or 17beta-estradiol on cell-matrix interactions in the endometrium of diabetic rats: relevance for hormone therapy, BP.PD

Abstract

Even though there are still many points to be investigated on phytohormones actions associated to reproductive functions, many clinicians and academic personnel treat postmenopausal women with those substances, especially isoflavones, as an alternative to estrogens intended to relieve the symptoms thereby associated. Surmounting diabetes mellitus is a major factor of complications, since female hormones have an important physiological interplay with e with other hormones, including insulin. The efficacy and safety of steroid hormonal therapy for post-menopausal women are a matter of controversy, since the use of estrogen involves a risk of developing cancer breast and hyperplasia of endometrium. Among the experimental models proposed to approach this subject, ovariectomized diabetic rats have been used in order to evaluate the effects of treatment with soy isoflavones on a menopausal condition, In addition, the effects of isoflavones on diabetic rats as they can be similar or not on normal rats is a relevant issue. Objective: to analyze the interactions between cells, extracellular matrix, cell differentiation, proliferation, adhesion, and migration, and angiogenesis, in the endometrium of diabetic rats treated with isoflavones and/or 17²-estradiol. Methodology: 60 female, adult rats (Rattus norvegicus albinus) will be divided into 6 groups, as follows: GI (n=10), control normal animals (sham-ovariectomized); GII (n=10), control diabetic animals (sham-ovariectomized); GIII (n=10), ovariectomized controls; GIV (n=10), ovariectomized diabetic animals; GV (n=10), ovariectomized diabetic animals treated with soybean isoflavones (150 mg/kg by gavage); GVI (n=10), ovariectomized diabetic animals treated with estrogen (17²-estradiol, 10 µg/kg, subcutaneously). Diabetes will be induced by streptozotocin (60 mg/kg). Treatments will last 30 days; at the end of the experiment the rats will be killed under deep anesthesia, the endometrium will be dissected out and processed for further RT reaction (RT-PCR) and Western blotting techniques. The results will be analyzed by one-way ANOVA followed by the Tukey's test. As a prospect, the results may contribute with new data to the project that is currently being developed in Brazil, with new insights on the role of endometrial extracellular matrix in the post-menopausal period, especially in diabetic patients. (AU)