Comparative study of the effects of protein restriction in utero and dexamethasone in vitro exposure during nephrogenesis: assessment of gene expression, of miRNAs, protein, and morphometric in metanephric mesenchyme
Both the protein-calorie malnutrition and hypertension represent global problems of public health. Epidemiologic studies in populations, as well as experimental results indicate that intrauterine nutritional conditions "program" the development of hypertension and coronary heart disease in adults. From these results has been showed that protein deprivation during pregnancy, an active period of nephrogenesis, causes reduction in the glomeruli number at birth. Thus, the predisposition to hypertension can be determined at least in part, by abnormal development of kidney. One of the factors involved in the genesis of fetal programming is the increased fetus exposure to maternal glucocorticoids. However it is not known whether this mechanism is also involved and undertakes the process of nephrogenesis. Recent studies show that the number of mesenchymal cap (CM) stem cells, around the edge of the shoot of the ureter, determines the final number of nephrons. The objectives of this project are: 1) assess the CM area and the rates of cells death and proliferation in CM, 2) gene and miRNAs expression; 3) number of positive cells for proteins controlling cell cycle, Bim protein and stem cells markers in the CM of the offspring of rats subjected to protein restriction during pregnancy, compared to their controls, at different periods of renal ontogenesis. Will also be checked the same parameters in cultured metanefros exposed to dexamethasone (DEX) mimicking fetal corticosteroids high concentration that has been verified in the gestational protein restriction models. The studies aim to associate both morphometric profile and gene expression to the nephron reduction observed in this model.
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