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Influence of food restriction during gestation and maternal glucocorticoids on offspring HPA axis with acute lung injury

Grant number: 18/10844-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2019
Effective date (End): July 31, 2020
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Richardt Gama Landgraf
Grantee:Pedro Henrique Severo
Home Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

Food restriction during gestation may prejudice the fetal growth and exposes the fetus to high maternal glucocorticoid concentrations, which may alters the development and program different disorders that present in adult life. Although data in literature showing the relashionship between maternal glucocorticoids exposure and dysregulation of HPA axis, with consequent hypercorticosterolemia in rats, beyond changes in morphology and lung function of the offspring, the mechanisms involved remain unknown. In the present study, pregnant female Wistar rats will receive 50% caloric-protein restriction througout the gestation and will be treated with metyrapone to reduce corticosterone concentrations. Will be evaluate the regulation of glucocorticoids and its interference on acute pulmonary inflammation of adult offspring at 12 weeks old. Acute lung injury will be induced by LPS; total and differential counts of leukocyte will be performed on the bronchoalveolar lavage of this offspring. The corticosterone and ACTH levels will be measure in serum, as well as the expression of glucocorticoid receptors and ACTH will be analyzed in the lung, hypothalamus and adrenal. The data obtained, besides possibly clarifying the mechanisms involved with the dysregulation of the HPA axis due to food restriction in utero, may contribute to clarification of immune system fetal programming and the inflammatory response to infections.