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Endoplasmic reticulum stress as modulator of placental response to maternal obesity: implications for the DOHaD hypothesis

Grant number: 20/16726-4
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): October 01, 2021
Effective date (End): May 31, 2023
Field of knowledge:Health Sciences - Nutrition - Malnutrition and Physiological Development
Principal Investigator:Letícia Ignácio de Souza Zimmermann
Grantee:Bruna de Souza Lima
Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil

Abstract

Pregnancy has imperative importance for maternal and fetal health. Nutritional and metabolic insults at this period how obesity or malnutrition, corroborating the DOHaD hypothesis, could includes placental changes from the oxidative stress mechanisms, inflammation, or endoplasmic reticulum stress (ERE). In addition, several UPR sensors have already been classified as essential for the development of the placenta and the viability of the embryo, which would be decisive for the success of the process. Thus, is consensus that obesity is an acute and subclinical inflammation, that the placenta is the most important maternal-fetal organ for the establishment and the adequate gestational outcome, and than ERE can be induced by inflammation, we intend to investigate, in an animal model of pregnancy during obesity induced by a high-fat diet, a modulation of the stress response of the endoplasmic reticulum as well as its relationship with the fetal outcome (fetal weight and size, weight and placental efficiency). For this, will perform an "in silico" analysis of the modulated genes in the RNASeq database previous generated by the research group for the pathways of interest. Besides, we aim to evaluate the modulation of this molecular mechanism "ex vivo" with pharmacological inhibitors of the pathway, and then we test it in an "in vivo" model to evaluate the fetal outcome. The results of this work will be unprecedented and that will provide with important subsidies for understanding the processes by which the maternal environment impacts on the development of the placenta and, consequently, on the development of the fetus.

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