EVALUATION OF THE HYPOXIA AND OXIDATIVE STRESS MARKERS IN THE MATERNAL ORGANISM AND PLACENTA OF RATS UNDER HYPERGLYCEMIC CONDITIONS

• Grant number: 11/14011-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): December 01, 2011
• Effective date (End): November 30, 2014
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Débora Cristina Damasceno
• Grantee: Yuri Karen Sinzato
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Diabetes mellitus (DM) is a frequent clinical condition, affecting around 7% of the population, and about 50% of patients with diabetes are unaware of the diagnosis. There is evidence that hyperglycemia induces an increase production of reactive oxygen species (ROS). The increased production of ROS by hyperglycemia is recognized as a major cause of clinical complications associated with diabetes. Women with gestational diabetes show the presence of oxidative stress in the mother and their placentas, because of the reduction in antioxidant defense mechanism and an increase of ROS production. Placenta is the active interface between the maternal and fetal circulation, regulating maternal physiological changes during pregnancy and fetal growth and plays an important role protecting the fetus through the adverse effects of maternal diabetes. Redox-sensitive transcription factors such as hypoxia-inducible factors (HIF) are identified as regulators of gene expression in response to changes in the concentration of ROS. The HIF proteins are among the transcription more defined and identified as being regulated by intracellular redox state. It has been shown that the activity of HIF is required for placental development by regulating the morphogenesis and vascularization of the fetal placenta and acting on the proliferation and differentiation of trophoblast. Although hypoxia is essential in early development, placental hypoxia during gestation is often involved as the cause or contributor to intrauterine growth restriction (IUGR) and diseases like diabetes. Despite the association between oxidative stress, hypoxia and placental alterations, there are no studies that relate these factors with pregnancies complicated by hyperglycemia. Human studies that explore mechanisms responsible for changes caused by diabetes are limited not only for ethical reasons, but also by the many uncontrollable variables that can modify the intrauterine environment and cause the potentiating effects of congenital malformations, such as diet, socioeconomic factors, nutrition and genetic factors. Thus, there is a need to prepare an appropriate experimental model. Therefore, models will be used to induce diabetes with different intensities (moderate and severe) to evaluate the mechanisms of hypoxia and oxidative stress in pregnancy in rats, focusing on the combination of these markers with placental development and fetal growth. This study will determine if changes in the growth of newborn at term pregnancy are related to early placental changes, aimed at the use of appropriate therapies to minimize these changes and contribute to a better perinatal outcome.