Endocrine disruptors versus hormonal receptors and cell survival: influence of a mixture based on human exposure on the dorsolateral prostate of Sprague-Dawley rats

• Grant number: 21/00075-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): April 01, 2021
• Effective date (End): December 31, 2021
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Leonardo de Oliveira Mendes
• Grantee: Maria Luiza Silva Ricardo
• Host Institution: Faculdade de Artes, Ciências, Letras e Educação de Presidente Prudente (FACLEPP). Universidade do Oeste Paulista (UNOESTE). Campus de Presidente Prudente. Presidente Prudente , SP, Brazil

Abstract

Endocrine disruptors (ED) are exogenous compounds dispersed in the environment that modify hormonal biosynthesis, causing several consequences for human health, including chronic diseases, such as cancer. In the last decade, special attention was directed to studies involving such compounds, however, most research does not adequately portray the exposure to which humans are subjected, focusing only on the evaluation of the effects of ED alone or in small groups. In addition, the short exposure intervals are also a limiting factor, since, in the case of tumor processes, the manifestation of the disease can occur years after contact with its etiological factor. Research that develops an experimental protocol that approaches human reality is necessary for a reliable characterization of environmental exposure and its reflexes on health / homeostasis. Thus, the aim of this proposal is to investigate the histopathological aspects of the dorsolateral prostate of rats exposed during pregnancy, lactation and even adulthood to a mixture of ED based on human exposure, relating to the expression of hormone receptors and cell survival. To achieve this objective, pregnant females of the Sprague-Dawley lineage will be divided into 2 experimental groups (control [vehicle] and Mix 100x, diluted in corn oil, by gavage), and exposed during pregnancy and lactation to a mixture consisting of 12 compounds that include phytates, pesticides, uv filters, in addition to bisphenol A, butylparaben. After weaning, male F1 generation puppies will continue to receive the complete ED mix until 180 days of age, when they will be euthanized. Plasma and prostatic tissue fragments will be collected for testosterone and estradiol measurements. The rest of the dorsolateral prostate will be used for histopathological, RTqPCR, immunohistochemistry and western blotting analyzes. After the proposed analyzes, it will be possible to assess whether chronic exposure to a mixture of ED is capable of destabilizing prostatic homeostasis.