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Evaluation of exposure-gene-disease triad: effects of endocrine disrupters mixture human relevant on the prostate microenvironment

Grant number: 18/24044-0
Support type:Regular Research Grants
Duration: November 01, 2019 - October 31, 2021
Field of knowledge:Biological Sciences - Morphology - Histology
Principal Investigator:Leonardo de Oliveira Mendes
Grantee:Leonardo de Oliveira Mendes
Home Institution: Pró-Reitoria de Pesquisa e Pós-Graduação. Universidade do Oeste Paulista (UNOESTE). Presidente Prudente , SP, Brazil
Assoc. researchers:Anthony César de Souza Castilho ; Wellerson Rodrigo Scarano

Abstract

Endocrine disruptors (ED) are exogenous compounds dispersed in the environment and that modify hormonal biosynthesis, implying consequences for human health, including genetic diseases, such as cancer. In the last decade, special attention has been directed to studies involving such compounds, but most researchers do not adequately portray the exposure to which humans are submitted, focusing only on the evaluation of the effects of isolated ED or small groups. In addition, exposure ranges are also a limiting factor, since in the case of tumor processes, a manifestation of the disease may occur years after contact with its etiological factor. A study that develops an experimental protocol that approaches human reality is necessary for a reliable characterization of the gene-environment interaction and its effects on human health. Thus, the present study aimed investigates the genetic and histopathological aspects of the ventral prostate of rats exposed during gestation, lactation and even adulthood to an ED mixture based on human exposure, relating to molecular changes observed in human prostate tumors deposited in databases. To reach this goal, Fisher 344 pregnant females will be divided into 3 experimental groups (control [vehicle], 100mg / kg/day group, 450mg / kg/day group) and expose during gestation and lactation to a mixture with 13 compounds which include phthalates, pesticides, UV filters, as well as bisphenol A, butylparaben and paracetamol. After weaning, F1 male pups will continue to receive the complete ED mixture until the 180 days old, when they will be euthanized. Plasma and prostatic tissue fragments will be collected for testosterone and estradiol measurements. The other part of the ventral prostate will be allocated to histopathological and molecular analyses by sequencing Generation (HigSeq-2500 Illumina) and RTqPCR for target validation. After the proposed analyzes, the data will be compared between the experimental groups and with the data deposited in the scientific literature, integrating the results and establishing possible molecular biomarkers that characterize the exposure-gene-environment triad. (AU)