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MOLECULAR EVALUATION OF PROSTATIC ESTROMAL COLLAGEN FROM RATS EXPOSED FOR A LONG PERIOD TO AN ENVIRONMENTALLY RELEVANT MIXTURE OF ENDOCRINE DISRUPTORS

Grant number: 24/00912-4
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2024
Effective date (End): April 30, 2025
Field of knowledge:Biological Sciences - Morphology - Histology
Principal Investigator:Leonardo de Oliveira Mendes
Grantee:Vitor de Oliveira Pinaffi
Host Institution: Faculdade de Medicina Dr Domingos Leonardo Ceravolo. Universidade do Oeste Paulista (UNOESTE). Campus de Presidente Prudente. Presidente Prudente , SP, Brazil

Abstract

Frequent exposure to endocrine disruptors (EDs) has caused an imbalance in the homeostasis of hormone-dependent organs, such as the prostate, triggering histopathological and molecular changes that can culminate in the emergence of chronic diseases, such as cancer. DEs are exogenous compounds found in the environment through the production of various everyday products, including plasticizers, herbicides, lubricants, solvents, among others. Continuous exposure to these substances can influence the process of prostate differentiation and the control of homeostasis, altering the metabolism of important structural components, such as collagen. Most studies evaluate the effects of EDs in a fragmented manner, distancing themselves from the environmental exposure to which human beings are subjected. In an attempt to address this issue, we will conduct molecular analyzes on the ventral prostate of rats exposed from intrauterine life (from gestational day 7 to postnatal day 21) until adulthood (from postnatal day 22 to postnatal day 220). to a mixture of twelve compounds (phythalates, pesticides, herbicides, fungicides, UV filters, bisphenol A, butylparaben (32.11 mg/kg/day) diluted in corn oil (2 ml/kg) and a control group (vehicle: corn oil, by gavage). This project is a part of the FAPESP Research Grant (2018/24044-0) and, therefore, the experimental design has already been carried out. The ventral prostate was collected, processed and expression will be carried out by RT -qPCR of collagen (type I and type III), metalloproteinases (MMPs - key components in the modulation of the extracellular matrix) and tissue metalloproteinase inhibitors (TIMPs), as well as the assessment of MMPs activity by zymography. Given that changes in these components are related to the destabilization of the organ's homeostasis, it is expected that long-term exposure to DEs is capable of altering collagen gene expression and also directly influencing the action of TIMPs and MMPs, impacting the organization of the extracellular matrix.

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