Role of high concentration of maternal corticosterone and possible epigenetic changes in acute lung inflammation of low birth weight rats

• Grant number: 20/16020-4
• Support Opportunities: Regular Research Grants
• Duration: August 01, 2021 - October 31, 2023
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Richardt Gama Landgraf
• Grantee: Richardt Gama Landgraf
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Associated researchers: Maristella de Almeida Vitta Landgraf ; Rogério Antônio Laurato Sertié ; Sandra Andreotti

Abstract

The maternal food restriction during gestation impair the fetal development and exposes the fetus to high levels of corticosterone, programming the development of diseases in adult life. The exposition to high levels of maternal corticosterone is related to HPA axis dysregulation and changes in morphology also lung function of offspring. Considering the epigenetic mechanisms are crucial for chromatin structure reprogramming and gene expression during development and cell differentiation, we hypothesized that molecular mechanisms, including epigenetic alterations due to global undernutrition throughout the gestational period might be involved in the mechanisms of the attenuation response in acute lung inflammation. In the present study, Wistar female rats with caloric-protein restriction througout pregnancy will be treated with metyrapone with the aim to reduce the corticosterone levels. The regulation of glucocorticoids and acute lung inflammation by LPS will be study in offspring with 12 weeks-old. The parameters of acute lung inflammation relevant to characterization will be evaluated. We propose the study of these mechanisms in a classic model of in utero malnutrition (characterized by a 50% reduction in diet during the every gestational period) and the use of current techniques that provide answers to both our hypothesis and the associated objectives. The data obtained may help in better understanding of fetal programming of non-transmissible inflammatory chronic diseases, as well in fetal programming of immunological system response. (AU)