Dna damage and its cellular response in pregnant women and newborns at different hyperglycemia levels

Abstract

The Research Group Diabetes and Pregnancy - Clinical and Experimental Research has been developing clinical and experimental research in this line for over 25 years.The results of these studies characterized the group of women who, despite the tolerance test glucose 100 g (GTT 100g) normal, have hyperglycemia as evidenced by changes in glycemic profile (GP). These women were classified as IB Rudge group, suffering from mild gestational hyperglycemia.In addition to other adverse perinatal outcomes (APO), characteristic of the children of diabetic mothers, the hyperglycemic pregnancies show a risk of perinatal death attributable to the comparable group of diabetic women (4.16% vs 6.12%) and therefore are treated as diabetic.The current literature has been recognizing that maternal hyperglycemia, independent of any intensity and diagnosis of gestational diabetes should be monitored by the APO risk. This validates the identification and treatment initiated more than 25 years, the IB Rudge group, carriers of mild gestational hyperglycemia.In studies of the factors involved in adverse outcome of pregnancies complicated by disorders of glucose, the results of our research group highlight the intrauterine hypoxia and maternal hyperglycemia of varying intensity. This association would lead to morphological and functional abnormalities of the placenta, characterized by impaired vascularization of the maternal-fetal area, increase and / or a decrease in markers of vascular proliferation and increased apoptosis and changes in cytokine profile.In parallel, our experimental results in rats with diabetes streptozotocin-induced showed other factors involved in the adverse outcome. The oxidative processes mediated by free radicals and increase overall damage DNA were directly dependent on the intensity of maternal hyperglycemia, reflected in the intrauterine environment.Among other factors, hyperglycemia and inflammation generate reactive oxygen species, leading to a state of oxidative stress and consequent DNA damage. If the cells have no capacity to DNA repair, there will be accumulation of mutations or the cell will death. The addition of molecular biology tools in our study was crucial to set new directions. Thus, a project of two post-doc students with a scholarship PNPD / CAPES is under development to explore the pathway of hypoxia and placental vasculature in pregnancies complicated by mild gestational diabetes and hyperglycemia. In this project are being evaluated protein and gene expressions of VEGF and PlGF and their receptors (VEGFR-1 and VEGFR-2) and iNOS, COX2, HIF-alpha and MCP1; concentrations of VEGF and PlGF and their receptors (VEGFR-1 and VEGFR-2) and iNOS and COX2 and MCP1 factor in placental homogenate and maternal serum (PNPD Project).These studies should be complemented by this project, with the exploration of potential changes in the DNA damage and DNA repair pathway, as a result also of hyperglycemia and hypoxia present in this pregnancies.In this context, this project's general objective is the investigation of lesions in DNA (nuclear and mitochondrial), the capacity for DNA repair and cell death, activated by lesions in pregnant women with varying degrees of hyperglycemia and its descendants. The development of this project should help to clarify the mechanisms involved and the consequent prevention of APO in these pregnancies, which justifies its proposal. In addition to scientific advances, this project will consolidate a partnership, already begun with researchers at the ICB, University of São Paulo, Estela Maris Andrade Forell Bevilacqua - Citofisiologia of the trophoblast Laboratory , and Carlos Frederico Martins Menck - The DNA repair laboratory.