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

Grant number: 11/13562-1
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2011
Effective date (End): February 28, 2015
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Iracema de Mattos Paranhos Calderon
Grantee:Jusciele Brogin Moreli
Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Associated scholarship(s):12/23296-0 - Damage in nuclear and Mitochondrial DNA in pregnant women and newborns at different hyperglycemia levels, BE.EP.DR

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.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MORELI, JUSCIELE B.; SANTOS, JANINE H.; LORENZON-OJEA, ALINE RODRIGUES; CORREA-SILVA, SIMONE; FORTUNATO, RODRIGO S.; ROCHA, CLARISSA RIBEIRO; RUDGE, MARILZA V.; DAMASCENO, DEBORA C.; BEVILACQUA, ESTELA; CALDERON, IRACEMA M. Hyperglycemia Differentially Affects Maternal and Fetal DNA Integrity and DNA Damage Response. International Journal of Biological Sciences, v. 12, n. 4, p. 466-477, 2016. Web of Science Citations: 6.
MORELI, JUSCIELE BROGIN; SANTOS, JANINE HERTZOG; ROCHA, CLARISSA RIBEIRO; DAMASCENO, DEBORA CRISTINA; MORCELI, GLILCIANE; RUDGE, MARILZA VIEIRA; BEVILACQUA, ESTELA; PARANHOS CALDERON, IRACEMA MATTOS. DNA Damage and Its Cellular Response in Mother and Fetus Exposed to Hyperglycemic Environment. BIOMED RESEARCH INTERNATIONAL, 2014. Web of Science Citations: 12.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
MORELI, Jusciele Brogin. Lesões no DNA e capacidade de resposta celular de gestantes e recém-nascidos em regime de hiperglicemia de intensidade variada. 2015. 53 f. Doctoral Thesis - Universidade Estadual Paulista "Júlio de Mesquita Filho" Faculdade de Medicina..

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