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Identification of oncogenic targets in the prostate of rats exposed to fatalate mixtures during perinatal development: transgerational study

Grant number: 19/13823-1
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2019
Effective date (End): February 28, 2023
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Wellerson Rodrigo Scarano
Grantee:Ariana Musa de Aquino
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The intrauterine microenvironment has been significantly altered due to the interference of environmental and/or socioeconomic factors, which can generate late and transgenerational consequences. Phthalates represent a class of molecules detected in different concentrations in breast milk, urine of pregnant women, amniotic fluid and human and rodents placenta. Previous studies have shown that perinatal exposure to isolated phthalates increases the susceptibility to prostatic carcinogenesis. The aim of this study was to investigate the gene expression profile of the rats exposed to a mixture of phthalates at different concentrations with a focus on possible oncogenic and/or developmental targets of animals exposed in the perinatal period (F1), as well as their offspring (F2). For this, pregnant rats of the Sprague Dawley line will be distributed randomly in 4 experimental groups: G1: (control, vehicle); G2: 20¼g/kg/day, G3: 200¼g/kg/day and G4: 200mg/kg/day (v.o. gavage); and exposed from gestational day 10 (DG10) to postnatal day 21 (DPN21). Male F1 generation rats will be euthanized at two times, at DPN22 and DPN120. Exposed females and males that are not euthanized (F1) will be mated with unexposed animals, and their offspring (F2) will be euthanized at PND22. The VP from F1 and F2 generations will be collected for the analysis of gene expression by sequencing (F1/DPN22) and by RTq-PCR (F1/DPN120 and F2/DPN22). According to gene expression profile, groups will be selected to proteomic profile study, in order to compare the gene and protein targets and to outline possible molecular mechanisms that may be related with treatment effects. (AU)