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Molecular characterization of fetal programming in gestational diabetes: obesity predisposition

Abstract

The concept of "fetal programming" has received special attention because it may interfere with factors related to the genesis and development of diseases in childhood, adolescence and adulthood. On the other hand, since literature shows that children from mothers with gestational diabetes mellitus (GDM) are at increased risk for developing obesity, becomes of great importance to characterize this stressor and to determine the mechanism(s) by which hyperglycemia acts. In this context, the objectives of the present study are to genetically classify women with Diabetes Mellitus (Gestational and type 2) and Mild Gestational Hyperglycemia (MGH) and to elucidate some of the mechanisms by which this disorder may predispose fetus/newborn to obesity. The project consists of two subprojects (Subprojects 1 and 2) that are complementary. Subproject 1 aims the characterization (gene expression profiling) of pregnant women with diabetes and mild hyperglycemia; Subproject 2 aims to identify in the fetus/newborn the toxicogenomics events induced by these metabolic disorders might which favor the development of obesity. The casuistic of the Subproject 1 include: Group1) Non-diabetic pregnant women (normal GTT and glycemic profile); Group 2) Pregnant women with MGH (normal TTG and altered glycemic profile); Group 3) Pregnant women with GDM (altered TTG and normal/altered glycemic profile); Group 4) Pregnant women with gestational and overt diabetes (altered TTG and glycemic profile). In the Subproject 2 will be included pregnant women with GDM (Group 1) and their respective newborns (Group 2), healthy pregnant women (Group 3) and their newborns (Group 4), and obese (Group 5) and eutrophic (Group 6) adults. The end-points to be assessed in blood cells and placenta are: gene expression profiling (microarrays) (Subprojects 1 and 2), microRNAs expression (Subproject 2) and gene methylation (Subproject 2). It is expected the genetic characterization of pregnant women with diabetes and MHG, and the identification of genetic and epigenetic changes in newborn cells allow to better understanding the relationship between hyperglycemia during pregnancy and obesity, and also to contribute to the establishment of strategies for preventing or reducing the risk of developing this metabolic disorder. (AU)

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)
DE CASTRO MARCONDES, JOAO PAULO; BERTOLINI ANDRADE, PABLO FELIPE; VENTURA SAVIO, ANDRE LUIZ; DATSCH SILVEIRA, MARUHEN AMIR; CUNHA RUDGE, MARILZA VIEIRA; FAVERO SALVADORI, DAISY MARIA. BCL2 and miR-181a transcriptional alterations in umbilical-cord blood cells can be putative biomarkers for obesity. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, v. 836, n. B, SI, p. 90-96, DEC 2018. Web of Science Citations: 1.
GELALETI, RAFAEL B.; DAMASCENO, DEBORA C.; SALVADORI, DAISY M. F.; CALDERON, IRACEMA M. P.; COSTA, ROBERTO A. A.; PICULO, FERNANDA; MARTINS, DAVID C.; RUDGE, MARILZA V. C. Gene expression profile of whole blood cells differs in pregnant women with positive screening and negative diagnosis for gestational diabetes. BMJ OPEN DIABETES RESEARCH & CARE, v. 4, n. 1 FEB 2016. Web of Science Citations: 1.

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