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IN VIVO ANALYSIS OF HYPOXIA AND OXIDATIVE STRESS RELATIONSHIP ON EMBRYOFETAL PANCREAS DEVELOPMENT OF THE DIABETIC RATS OFFSPRING

Grant number: 11/23642-2
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2012
Effective date (End): February 28, 2015
Field of knowledge:Health Sciences - Medicine - Maternal and Child Health
Principal researcher:Débora Cristina Damasceno
Grantee:Isabela Lovizutto Iessi
Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Introduction: Diabetes in pregnancy results in hormonal and metabolic disorder altering intrauterine environment, leading to maternal and fetal complications, which may contribute for repercussions in adult life. Hyperglycemia increases the production of reactive oxygen species (ROS), which is a major cause of clinical complications associated with diabetes. The embryos and fetus are susceptible to changes in oxygen tension. Hypoxia-inducible factors (HIF) are identified as regulators of gene expression products that exhibit antioxidant activity in response to the presence of ROS. The partial oxygen tension regulates the embryonic development of several organs, including pancreas. Pdx-1 is a transcription factor required of the pancreatic development. The inactivation of Pdx-1 in ² cells in late gestation result in decreased proliferation of these cells. Iessi (2012) showed that offspring of rats exposed to hyperglycemic intrauterine environment presented alterations in pancreatic hormones (glucagon and somatostatin) levels at birth. In neonatal period, somatostatin levels remained changed, in contrast of glucagon and insulin levels. These results demonstrated that somatostatin was more susceptible to changes, and possibly may be used as predictor of adverse effects at adulthood. Objective: To evaluate oxidative stress status and hypoxia on embryofetal pancreatic development in hyperglycemic conditions. Material and Method: The pancreas of embryos of the Wistar rats (non-diabetic, mild diabetes and severe diabetes) will be studied on days 11.5, 18.5 and 21.5° of pregnancy by immunohistochemical analysis of endocrine hormones (somatostatin, glucagon and insulin), proliferative index (Ki67) and Pdx-1 and gene and protein expression of hypoxia (HIF-1 alpha) and oxidative stress (superoxide dismutase, catalase and glutathione peroxidase) markers using real time qRT-PCR and Western blotting, respectively. Goal: To identify the biological markers related to oxidative stress and hypoxia with the embryonic and pancreatic development to future interventions aiming to reduce the perinatal adverse outcomes found in the diabetic state.

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
IESSI, Isabela Lovizutto. Análise in vivo da relação entre hipóxia e estresse oxidativo sobre o desenvolvimente embriofetal do pâncreas de descendentes de ratas diabéticas. 2015. 27 f. Doctoral Thesis - Universidade Estadual Paulista "Júlio de Mesquita Filho" Faculdade de Medicina..

Please report errors in scientific publications list by writing to: cdi@fapesp.br.