Effects of supplementation with sex steroids on females induced to carcinogenesis and exposed to Bisphenol A: analysis in mammary glands

• Grant number: 23/15426-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2024
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Sebastião Roberto Taboga
• Grantee: Rafael Henrique Borges Coelho
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

The mammary gland is an organ susceptible to hormonal changes according to the different stages of life and female estrous cycles. Among the hormones that interact to cause these cyclic modifications, estrogens and progesterone act as protagonists in epithelial and stromal alterations. However, women are subject to endocrine disruptors present in the environment and hormonal therapies, such as bisphenol A (BPA) (an environmental contaminant) and exogenous estrogens, respectively. Therefore, the present study aims to analyze the effects caused by the interaction between these endocrine disruptors in order to enhance carcinogenesis in mammary tissue. Thus, the study will be conducted on adult female Mongolian gerbils (Meriones unguiculatus) exposed to BPA during the perinatal period and induced to carcinogenesis by N-ethyl-N-nitrosourea (ENU) in adulthood. After pro-carcinogenic exposure, the animals will be treated with 17-²-estradiol (E2) and 17-±-ethinylestradiol (EE2 - 0.2 mg/kg), two forms of estrogens. Control groups without treatment will also be included, consisting of animals only exposed to perinatal BPA (without pro-carcinogenic treatment). This experiment aims to observe the effects of estrogenic compounds commonly used in hormonal therapies, such as contraceptives and supplementation, in a microenvironment of endocrine disruption and carcinogenic potentiation. Histopathological analyses will be performed to assess the incidence of lesions and the dynamics of cell proliferation and death using markers such as phospho-histone H3 (PHH3) and caspase 3, respectively. Additionally, molecular analyses and the expression of estrogen receptors (ER± and ER²) and progesterone will be conducted. The goal of this project is to contribute to the understanding of carcinogenic development in the mammary gland in the presence of estrogenic stimulation under endocrine disruption.