Fetal programming: on the kidney and neural ontogenesis

• Grant number: 13/12486-5
• Support Opportunities: Regular Research Grants
• Duration: February 01, 2015 - April 30, 2017
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Jose Antonio Rocha Gontijo
• Grantee: Jose Antonio Rocha Gontijo
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Patrícia Aline Boer

Abstract

Subproject 1: Effects of protein restriction in the uterus and exposure to dexamethasone and ncotine in vitro during the nephrogenesis: morphometric and evaluation of gene expression and protein content in stem cells of the cap metanefrogênico. Epidemiological Evidence in diverse populations, as well as experimental results indicates that the nutritional intrauterine conditions "program" the development of hypertension and coronary heart disease in adults. From these results it appears that the gestational, protein deprivation during the active period of nephrogenesis, reduction in the number of clusters at birth. In this way, the predisposition to arterial hypertension can be determined at least in part, by the abnormal development of the kidneys. One of the factors involved in the genesis of fetal programming is the increased exposure of the fetus to the maternal glicocorticoides. However, it is not known if this mechanism is also involved and committed the nephrogenesis process. Recent studies show that the number of stem cells present in the cap mesenchymal (CM), around the end of the bud of the ureter, determines the number of nephron formed. The objective of this subproject is to check the area and the death index and cell proliferation of the cap, the gene expression and the number of positive cells for proteins cell cycle controllers and stem cell marker in CM of the offspring of rats submitted to protein restriction dates, compared to their controls, in different periods of ontogeny. Will still be checked the same parameters in metanephros exposed to dexamethasone (DEX) and nicotine mimicking the high concentration of fetal corticosteroids has demonstrated in gestational protein restriction and smoking. The studies aim to associate the morphometric and gene expression profiles to nephron, as observed in this model. Subproject 2. Analysis of the neural effects of protein restriction in the uterus: morphological and functional and molecular Study during the organogenesis and in adult male rats. Faced with a stressor, the classic answer of "flight or fight" is initiated by activation of the hypothalamic-pituitary-adrenal (HHA), with production of secretory hormone corticotropin-releasing hormone (CRH) and pituitary release of vasopressin and CORTICOTROPIN (ACTH) by the anterior pituitary. This stimulates the adrenal cortex, leading to temporary elevation of circulating corticosteroids. At the same time occurs activation of the autonomic nervous system and increased secretion of catecholamines, which, along with the glucocorticoid and other neuropeptides, contribute to an adequate response to stress. This translates, behaviorally, with an increase in alertness, vigilance and attention. Gradually arise the effects of gene regulation mediated by corticosteroid, through action on mineralo-receptors (MR) and glicocorticoides (GR), expressed in various brain structures. The mineralocorticoid receptors are responsible for the maintenance of excitability and structural integrity of neural networks and are still involved in the process of evaluation of sensory information and your organization. In turn, the glicocorticoides receptors are associated with the end of the response to stress, normalization of homeostasis and storing useful information for future events. These central changes during ontogeny are still poorly understood neural. Thus, taking into account the involvement of the hippocampus in a series of behavioral actions and its modulatory role of response to stress, the present study aims to assess the structural impact of a nutritional stress during pregnancy, relevant to a number of human diseases, not only at the level of the morphology of dendritic tree of pyramidal neurons, but also at the level of synaptic contacts established proximal and distal. (AU)

Scientific publications

(13)

(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)

LAMANA, GABRIELA LEME; FERRARI, ANA LETICIA LUCHIARI; GONTIJO, JOSE ANTONIO ROCHA; BOER, PATRICIA ALINE. Gestational and Breastfeeding Low-Protein Intake on Blood Pressure, Kidney Structure, and Renal Function in Male Rat Offspring in Adulthood. FRONTIERS IN PHYSIOLOGY, v. 12, APR 22 2021. (13/12486-5, 15/00360-2)

RIZZI, V. H. G.; SENE, L. D. B.; FERNANDEZ, C. D. B.; GONTIJO, J. A. R.; BOER, P. A.. Impact of long-term high-fat diet intake gestational protein-restricted offspring on kidney morphology and function. JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE, v. 8, n. 1, p. 89-100, FEB 2017. (13/12486-5)

ROZA, NOEMI A. V.; POSSIGNOLO, LUIZ F.; PALANCH, ADRIANNE C.; GONTIJO, JOSE A. R.. Effect of long-term high-fat diet intake on peripheral insulin sensibility, blood pressure, and renal function in female rats. FOOD & NUTRITION RESEARCH, v. 60, 2016. (13/12486-5)

CUSTODIO, AUGUSTO H.; DE LIMA, MARCELO C.; VACCARI, BARBARA; BOER, PATRICIA A.; GONTIJO, JOSE A. R.. Renal sodium handling and blood pressure changes in gestational protein-restricted offspring: Role of renal nerves and ganglia neurokinin expression. PLoS One, v. 12, n. 6, JUN 20 2017. (13/12486-5)

ASSALIN, HELOISA BALAN; ROCHA GONTIJO, JOSE ANTONIO; BOER, PATRICIA ALINE. miRNAs, target genes expression and morphological analysis on the heart in gestational protein-restricted offspring. PLoS One, v. 14, n. 4, APR 29 2019. (13/12486-5)

GOMES, JULIA SEVA; SENE, LETICIA BARROS; LAMANA, GABRIELA LEME; BOER, PATRICIA ALINE; GONTIJO, JOSE ANTONIO ROCHA. Impact of maternal protein restriction on Hypoxia-Inducible Factor (HIF) expression in male fetal kidney development. PLoS One, v. 18, n. 5, p. 18-pg., 2023-05-04. (13/12486-5, 14/50938-8, 12/18492-4)

SENE, LETICIA DE BARROS; LAMANA, GABRIELA LEME; VIEIRA, ANDRE SCHWAMBACH; SCARANO, WELLERSON RODRIGO; ROCHA GONTIJO, JOSE ANTONIO; BOER, PATRICIA ALINE. estational Low Protein Diet Modulation on miRNA Transcriptome and Its Target During Fetal and Breastfeeding Nephrogenesi. FRONTIERS IN PHYSIOLOGY, v. 12, JUN 22 2021. (13/12486-5, 14/50938-8, 12/18492-4)

MARIANO, VINICIUS SCHIAVINATTO; BOER, PATRICIA ALINE; GONTIJO, JOSE ANTONIO ROCHA. Fetal Undernutrition Programming, Sympathetic Nerve Activity, and Arterial Hypertension Development. FRONTIERS IN PHYSIOLOGY, v. 12, NOV 17 2021. (15/00360-2, 13/12486-5)

CARDOSO, BARBARA VACCARI; CUSTEDIO, AUGUSTO HENRIQUE; BOER, PATRICIA ALINE; ROCHA GONTIJO, JOSE ANTONIO. Effect of intracerebroventricular epinephrine microinjection on blood pressure and urinary sodium handling in gestational protein-restricted male adult rat offspring. BIOLOGY OPEN, v. 8, n. 4, APR 2019. (13/12486-5)

TORRES, D. B.; LOPES, A.; RODRIGUES, A. J.; CERQUEIRA, J. J.; SOUSA, N.; GONTIJO, J. A. R.; BOER, P. A.. Anxiety-like behavior and structural changes of the bed nucleus of the stria terminalis (BNST) in gestational protein-restricted male offspring. JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE, v. 9, n. 5, p. 536-543, OCT 2018. (13/12486-5)

SENE, LETICIA DE BARROS; SCARANO, WELLERSON RODRIGO; ZAPPAROLI, ADRIANA; ROCHA GONTIJO, JOSE ANTONIO; BOER, PATRICIA ALINE. Impact of gestational low-protein intake on embryonic kidney microRNA expression and in nephron progenitor cells of the male fetus. PLoS One, v. 16, n. 2, FEB 5 2021. (13/12486-5, 14/50938-8)

SENE, LETICIA B.; GONCALVES RIZZI, VICTOR HUGO; GONTIJO, JOSE A. R.; BOER, PATRICIA A.. Gestational low-protein intake enhances whole-kidney miR-192 and miR-200 family expression and epithelial-to-mesenchymal transition in rat adult male offspring. Journal of Experimental Biology, v. 221, n. 10, MAY 2018. (09/54141-9, 13/12486-5)

TORRES, DANIELE B.; LOPES, AGNES; RODRIGUES, ANA J.; LOPES, MARCELO G.; VENTURA-SILVA, ANA P.; SOUSA, NUNO; GONTIJO, JOSE A. R.; BOER, PATRICIA A.. Gestational protein restriction alters early amygdala neurochemistry in male offspring. NUTRITIONAL NEUROSCIENCE, v. N/A, p. 17-pg., 2022-10-26. (13/12486-5)