Effect of gestational exposure to TCDD on the development of type I diabetes in offspring

• Grant number: 17/02451-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2017
• End date: June 30, 2018
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Camila Peres Buzalaf
• Grantee: Bruno Henrique Serotini
• Host Institution: Pró-Reitoria de Pesquisa e Pós-Graduação. Universidade do Sagrado Coração (USC). Bauru , SP, Brazil

Abstract

Dioxins represent an important class of environmental contaminants. One representative of this class, 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) is produced anthropogenically in industrial processes, fires, and combustion processes such as incineration of health care waste, urban waste , Industrial waste, and motor vehicles. The major sources of human exposure to TCDD occur through the food chain, through ingestion of contaminated food and water, and occupational exposure. Several studies have suggested that their exposure during adulthood has an effect on the increased incidence of various metabolic, reproductive, and oncogenic disorders, as well as promoting immunomodulation and increasing the predisposition to the development of autoimmune diseases such as type I diabetes. , It is still unknown whether the exposure of TCDD during the prenatal period alters the immune cells well the mediators produced in the context of an autoimmune disease in adult life. Thus, the present project aims to evaluate the effect of the exposure of pregnant female mice to TCDD on the autoimmune response to type I diabetes of the offspring. For this, in C57BL / 6 female mice treated with streptozotocin and NOD mice (Non Obese Diabetic) exposed to TCDD during pregnancy, we will evaluate in the offspring the glycemia and insulinemia, the morphology and the expression of insulin in the pancreatic tissue, the cell death In situ and the determination of the insulin, the Th1, Th17 and Treg lymphocyte profile in the pancreatic and pancreatic lymph nodes by flow cytometry and the quantification of IFN-³, TNF-±, IL-17 and IL-10 cytokines in culture Of macrophages obtained from total cells of the bone marrow and in the homogenate of the pancreas. It is hoped to understand the basics of the immunological changes caused during prenatal exposure to TCDD, which persist in adult life in two models of autoimmune diabetes. (AU)