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Effects of the type 1 diabetes on the fetal reprogramming with focus on the glomerular extracellular matrix in mice model

Grant number: 15/03525-2
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2015
Effective date (End): November 30, 2019
Field of knowledge:Biological Sciences - Morphology - Embryology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Telma Maria Tenório Zorn
Grantee:Mychel Raony Paiva Teixeira Morais
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):17/26785-5 - Global analysis of enriched glomerular extracellular matrix of pre-term foetuses of normoglycemic and hyperglycaemic mothers using mass spectrometry-based proteomics, BE.EP.DR

Abstract

Over the past years, the Laboratory of Reproduction and Extracellular Matrix Biology had focused their studies on the complex remodeling process of the uterine extracellular matrix (ECM) during the estrous cycle and the development of the decidua in rodents. Through many morphological studies and molecular approaches, our group demonstrated that this remodeling process includes a series of cellular and molecular adaptations that lead to the establishment of the maternal-fetal interface and influence the entire uterine environment. Recently, our group has developed a model of pregnancy complicated by long-term type 1 diabetes mellitus (DM1) in mice. Using this model, we demonstrate that the uterine and placental ECM undergoes major alterations in their organization and macromolecular composition which compromise the pregnancy establishment and the embryonic implantation rate. Studies had shown the long exposure to maternal hyperglycemia during the intrauterine development impairs the early embryonic differentiation and organogenesis. This abnormal development predisposes the offspring of diabetic mothers to manifest several chronic diseases early in adulthood, like as hypertension and renal insufficiency due to structural defects in the organ and failures in the vascular and renal function. This phenomenon is known as fetal reprogramming. In this context, our hypothesis is that the abnormal maternal metabolism may promote a reprogramming of the glomerular development due to hyperglycemia-induced alterations in the synthesis, deposition and degradation of ECM macromolecules with potential to compromise the proper renal function. Thus, the aim of this project is to analyze the effects of the maternal DM1 on the composition and organization pattern of the main collagen and proteoglycan molecules of the glomerular ECM using our model of gestation complicated by DM1 in mice. (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)
NAYLOR, RICHARD W.; MORAIS, MYCHEL R. P. T.; LENNON, RACHEL. Complexities of the glomerular basement membrane. NATURE REVIEWS NEPHROLOGY, v. 17, n. 2 AUG 2020. Web of Science Citations: 0.

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