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 Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: October 01, 2018
• End date: March 31, 2019
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Luis Antonio Justulin Junior
• Grantee: Ana Carolina Lima Camargo
• Supervisor: Carlos Sanchez Moreno
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Institution abroad: 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.

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)

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)