Integrative global analyzes of the rat ventral prostate submitted to maternal protein restriction and its repercussions with aging

• Grant number: 17/01063-7
• Support Opportunities: Regular Research Grants
• Duration: October 01, 2017 - September 30, 2019
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Luis Antonio Justulin Junior
• Grantee: Luis Antonio Justulin Junior
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated researchers: Guilherme Targino Valente ; Robson Francisco Carvalho

Abstract

IIn the last decades, it has been observed an increase in the incidence of diseases related to changes in the metabolism, that affect both children and adults. Among the most prevalent are obesity, diabetes, cardiovascular diseases and even some types of cancer. Epidemiological evidence shows that chronic diseases can be originate from insults occured during intrauterine development, a condition known as Fetal Programming (PF). Despite this, the molecular mechanisms involved in this process are poorly understood. In this context, the advance of large-scale sequencing technologies based on the combination of "omics" (transcriptome, MicroRNoma, proteome) associated with bioinformatics tools has enabled a global integrative view of the molecular mechanisms under normal and pathological conditions. Considering results from our group that demonstrate the role of maternal protein restriction in altering the development and increasing the incidence of prostatic lesions in the offspring of rats, the objective of this work will be to identify the global expression profile of microRNAs (microRNA) and methylation, gene (transcriptome) and protein (proteome) in rat prostate samples that have undergone perinatal protein restriction, and to verify if possible alterations may be related to the molecular pathways involved in the development of prostatic lesions during aging. For this, Sprague Dawley male rats with 21 days of postnatal age born to mothers fed standard ration (17% protein) or with hypoprotein ration (6% protein) during gestation and lactation will be euthanized with an anesthetic overdose and the ventral prostate will be collected. It will be analysed the global methylation profiles by ELISA (Cell Biolabs - STA380), the expression of microRNAs (microRNA), the latest generation sequencing transcriptome (HigSeq-2000 Illumina) and the proteome, by mass spectrometry (LC-Ms/Ms). After this, an integrative and comparative analysis of these data will be performed between the experimental groups. These results will be compared to database from the transcriptome and proteome for prostatic adenocarcinoma available in the literature. Other animals will be euthanized at 540-day old. In these animals, it will be investigated whether the differentially expressed targets observed at 21 days (after the gestational and lactational protein restriction) remain altered and if they participate in the increase in the incidence of prostatic lesions observed at 540 days, as previously demonstrated by our group.Thus, it is expected to obtain an overview of the effects of fetal programming by protein restriction on prostatic biology, to identify molecular pathways altered during development and its repercussions with aging. (AU)

Scientific publications

(6)

(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)

FELISBINO, SERGIO LUIS; AZEVEDO SANCHES, BRUNO DOMINGOS; DELELLA, FLAVIA KARINA; SCARANO, WELLERSON RODRIGO; ALCANTARA DOS SANTOS, FERNANDA CRISTINA; LEITE VILAMAIOR, PATRICIA SIMONE; TABOGA, SEBASTIAO ROBERTO; JUSTULIN, LUIS ANTONIO. Prostate telocytes change their phenotype in response to castration or testosterone replacement. SCIENTIFIC REPORTS, v. 9, MAR 6 2019. (17/01063-7, 14/26660-0)

PORTELA, LUIZ M. F.; SANTOS, SERGIO A. A.; CONSTANTINO, FLAVIA B.; CAMARGO, ANA C. L.; COLOMBELLI, KETLIN T.; FIORETTO, MATHEUS N.; BARQUILHA, CAROLINE N.; PERICO, LARISSA L.; HIRUMA-LIMA, CLELIA A.; SCARANO, WELLERSON R.; et al. Increased oxidative stress and cancer biomarkers in the ventral prostate of older rats submitted to maternal malnutrition. Molecular and Cellular Endocrinology, v. 523, MAR 1 2021. (17/01063-7, 16/08789-0)

CAMARGO, ANA C. L.; REMOLI, BEATRIZ; PORTELA, LUIZ M. F.; FIORETTO, MATEUS N.; CHUFFA, LUIZ G. A.; MORENO, CARLOS S.; JUSTULIN, LUIS A.. Transcriptomic landscape of male and female reproductive cancers: Similar pathways and molecular signatures predicting response to endocrine therapy. Molecular and Cellular Endocrinology, v. 535, SEP 15 2021. (18/09408-6, 17/01063-7, 17/08715-0)

ALCANTARA SANTOS, SERGIO ALEXANDRE; LIMA CAMARGO, ANA CAROLINA; CONSTANTINO, FLAVIA BESSI; COLOMBELLI, KETLIN THASSIANI; FREDIANI PORTELA, LUIZ MARCOS; FIORETTO, MATHEUS NAIA; SOUZA VIEIRA, JOSE CAVALCANTE; PADILHA, PEDRO MAGALHAES; DE OLIVEIRA, MATEUS BETTA; FELISBINO, SERGIO LUIS; et al. Identification of potential molecular pathways involved in prostate carcinogenesis in offspring exposed to maternal malnutrition. AGING-US, v. 12, n. 20, p. 19954-19978, OCT 31 2020. (17/08715-0, 17/01063-7, 14/08531-8)

SANTOS, SERGIO ALEXANDRE ALCANTARA; PORTELA, LUIZ MARCOS FREDIANI; CAMARGO, ANA CAROLINA LIMA; CONSTANTINO, FLAVIA BESSI; COLOMBELLI, KETLIN THASSIANI; FIORETTO, MATHEUS NAIA; MATTOS, RENATO; FANTINATTI, BRUNO EVARISTO DE ALMEIDA; DENTI, MICHELA ALESSANDRA; PIAZZA, SILVANO; et al. miR-18a-5p Is Involved in the Developmental Origin of Prostate Cancer in Maternally Malnourished Offspring Rats: A DOHaD Approach. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 23, p. 17-pg., 2022-12-01. (19/03121-0, 17/25198-9, 17/01063-7)

SANTOS, SERGIO A. A.; CAMARGO, ANA C.; CONSTANTINO, FLAVIA B.; COLOMBELLI, KETLIN T.; MANI, FERNANDA; RINALDI, JAQUELINE C.; FRANCO, SUELEN; PORTELA, LUIZ M. F.; DURAN, BRUNO O. S.; SCARANO, WELLERSON R.; et al. Maternal Low-Protein Diet Impairs Prostate Growth in Young Rat Offspring and Induces Prostate Carcinogenesis With Aging. JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, v. 74, n. 6, p. 751-759, JUN 2019. (14/08531-8, 17/01063-7, 13/24230-5)