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EVALUATION OF THE IMPACT OF TYPE 1 DIABETES UPON THE RESPONSIVINESS OF UTERINE TISSUES TO ESTROGEN STIMULATION

Grant number: 11/22429-3
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): April 01, 2012
Effective date (End): March 31, 2016
Field of knowledge:Biological Sciences - Morphology - Histology
Principal Investigator:Telma Maria Tenório Zorn
Grantee:Rodolfo Favaro Ribeiro
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):14/23517-1 - Does type 1 diabetes change the microRNA expression profile on the uterus of ovariectomized mice submitted or not to estrogen replacement?, BE.EP.PD

Abstract

The Laboratory of Reproductive and Extracellular Matrix Biology has been working, since your criation in 1981, to investigate the cellular and molecular adaptations of the extracellular matrix (ECM) that the uterine environment undergoes during the reproductive cycle and early pregnancy, aiming to identify and understand the necessary requirements to implantation and embryo development. Our studies have shown that the establishment of maternal-fetal interactions requires intense uterine ECM remodeling (Review in: Abrahamsohn e Zorn, 1993; Abrahamsohm et al., 2002) and that this is finely regulated by ovarian hormones (Salgado et al., 2009; Salgado et al., 2011 (FAPESP: 10/52543-0 - Research Grants)). During my Phd project (FAPESP: 04/14442-6 - DD), our group established a new mouse model of pregnancy complicated by type 1 diabetes, specifically delineated to study the effects of this disease upon reproductive processes and originated a new research line in the laboratory (FAPESP: Processo: 07/55277-6 - Research Grants). By means of the model, we showed that diabetes promotes important molecular and structural, in particular in the ECM, and cell proliferation alterations on the uterine environment during pregnancy, with potentiality to impair implantation, embryo development and labor (Favaro et al., 2010; Favaro et al., submitted). From these discoveries, the hypothesis to the present work is that alterations promoted by diabetes on the uterine environment impair the responsiveness of the uterine tissues to hormonal stimulation. In order to test this hypothesis, we will integrate the two main lines of research being developed in our laboratory by applying the following approaches: i) we will submit our model of type 1 diabetes to ovariectomy and hormonal replacement; ii) we will investigate the responsiveness of uterine tissues to estrogen stimulation; iii) by proving our hypothesis, we will investigate the molecular mechanisms involved. For this, the following will be analyzed: i) the levels of estrogen receptor (ER) isoforms, ER± and ER²; ii) the ECM remodeling by analyzing the expression of its components and the activity of matrix metalloproteinases (MMPs); iii) the cell proliferation of the uterine tissues associated to the expression of genes that control cell cycle.

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)
PHOTINI, STELLA MARY; CHAIWANGYEN, WITTAYA; WEBER, MAJA; AL-KAWLANI, BOODOR; FAVARO, RODOLFO R.; JESCHKE, UDO; SCHLEUSSNER, EKKEHARD; MORALES-PRIETO, DIANA M.; MARKERT, UDO R. PIM kinases 1, 2 and 3 in intracellular LIF signaling, proliferation and apoptosis in trophoblastic cells. Experimental Cell Research, v. 359, n. 1, p. 275-283, OCT 1 2017. Web of Science Citations: 6.
ZORN, TELMA M. T.; FAVARO, RODOLFO R.; SOTO-SUAZO, MAURICIO; STUMPF, WALTER E. Mapping of estradiol binding sites through receptor micro-autoradiography in the endometrial stroma of early pregnant mice. Histochemistry and Cell Biology, v. 148, n. 3, p. 257-272, SEP 2017. Web of Science Citations: 0.
SANCHES, JULIANE C.; FAVARO, RODOLFO R.; BARRENCE, FERNANDA C.; BEVILACQUA, ESTELA; FORTES, ZULEICA B.; ZORN, TELMA M. T. Distinct effects of short- and long-term type 1 diabetes to the placental extracellular matrix and fetal development in mice. Placenta, v. 53, p. 1-7, MAY 2017. Web of Science Citations: 1.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.