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RNA-seq analysis to identify molecular targets involved in deregulation of prostate morphogenesis in rat offspring submitted to maternal low protein diet

Grant number: 18/09408-6
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): October 01, 2018
Effective date (End): March 31, 2019
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Luis Antonio Justulin Junior
Grantee:Ana Carolina Lima Camargo
Supervisor abroad: Carlos Sanchez Moreno
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Local de pesquisa : Emory University, United States  
Associated to the scholarship:17/08715-0 - Integrative analysis of the transcriptome and proteomics of the ventral prostate of rat offspring submitted to maternal protein restriction, BP.DR

Abstract

Maternal exposure to a protein-deficient diet during pregnancy, which is characteristic of underdeveloped countries and countries whose diet contains high-calorie, fiber-poor and nutrient foods, is associated with the development of diseases in the offspring, especially cardiovascular, renal, metabolic, and even cancer. Studies show that insults sustained during intrauterine development can trigger diseases related to changes in metabolism affecting both children and adults, a condition known as Fetal Programming (FP). In addition, our research group has demonstrated that maternal protein restriction influences prostate development in animals after birth and increases the incidence of prostate lesions in offspring to aging. Despite this, the molecular mechanisms that trigger these changes are still poorly understood. In this context, the advancement of large-scale sequencing technologies based on the combination of "omas" (transcriptome, MicroRNoma and proteome) using bioinformatics tools has enabled a global integrative view of molecular mechanisms under normal and pathological conditions. Thus, the aim of this work will be to identify the global expression profile of messenger RNAs (transcriptome) in prostate samples from rats that underwent perinatal protein restriction and to integrate the overall expression profile of mRNAs to identify regulation networks and molecular pathways involved in development prostate cancer in normal and restricted animals. Male rats of the 21-day postnatal Sprague Dawley line were born from mothers fed standard ration (17% protein) or from mothers fed with low protein (6% protein) during gestation and lactation. After this period, the animals were euthanized with heavy anesthetic overdose and the ventral (VP) prostate collected. The latest generation sequencing was performed by HigSeq-2500, Illumina. These results will be analyzed and compared to the transcriptome data for prostatic adenocarcinoma (TCGA), available in the literature, in order to investigate if the perinatal protein restriction is responsible for altering the gene expression of targets related to the development of prostatic lesions. With this, it is expected to obtain an overview of the effects of perinatal protein restriction on prostate biology.