Carcinogenesis in the ventral prostate of offspring older rats exposed to maternal low protein diet: role of microRNAs

• Grant number: 19/03121-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): September 01, 2019
• Effective date (End): March 01, 2020
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Luis Antonio Justulin Junior
• Grantee: Sérgio Alexandre Alcantara dos Santos
• Supervisor: Michela Alessandra Denti
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Research place: Universitá degli Studi di Trento, Italy
• Associated to the scholarship: 17/25198-9 - Maternal protein restriction and prostate carcinogenesis: integrative approaches based on omics analysis, BP.PD

Abstract

In the last decades, it has been observed an increase in the incidence of metabolic disorders, such as obesity, diabetes and even some types of cancer. Epidemiological evidences show that these diseases can originate from insults suffered by individuals during the intrauterine life, a condition known as Fetal Programming (FP). However, the molecular mechanisms involved in this process are poorly understood. In this context, the increase of large-scale sequencing technologies based on the combination of "omes" (transcriptome, MicroRNAome) using bioinformatics tools has enabled a global integrative view of molecular mechanisms in normal and pathological conditions. Considering the results from our group that demonstrated the role of maternal low protein diet in altering development and increasing the incidence of prostatic lesions in older rat offspring, the objective of this study will be to analyze the global expression of microRNAs (microRNoma) in offspring rat prostate born from dams fed low protein diet during gestation and lactation, to identify molecular pathways involved in the development of prostatic lesions. For that, male offspring rat (540 days old) born from dams fed standard diet (17% protein) or with low protein diet (6% protein) during gestation and lactation will be used. After this period, the animals will be euthanized, and the ventral prostate will be collected. Global expression profiles of microRNAs were analyzed by next-generation sequencing (HigSeq-2500 Illumina). After this, we will perform a comparative analysis of these data with databases between the experimental groups. These results will be compared to microRNA data for prostatic adenocarcinoma, available in the Databases. This application for a postdoctoral fellowship is linked to a regular FAPESP grant (Proc. 2017/01063-7) which aims to investigate, through global analyzes, possible altered molecular mechanisms in the offspring rats at 21 days old and that could lead to the higher incidence of lesions observed in these rats with aging. With the development of these projects, our group will obtain robust data on a large scale, not only from altered molecular pathways during the early stages of development, but also from the late repercussions of this fetal programming model. (AU)