Effects of Bisfenol A Exposure at Aging and the Reactive Stroma: Cell Types and Growth Factors Analysis in Mammary Gland

• Grant number: 23/16098-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2024
• End date: July 31, 2024
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Sebastião Roberto Taboga
• Grantee: Gervásio Evangelista Brito Filho
• 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

Mammary glands are constituted of glandular epithelial cells and myoepithelial cells, and in the stromal region, fibroblasts, and inflammatory cells. Its development and activity are mainly influenced by the endocrine system. The acquisition of the reactive stroma phenotype is observed when there are disturbances in stromal homeostasis, leading to changes in extracellular matrix composition, with occurrence of reactive cell types. One of the triggers of these alterations is endocrine-disrupting chemical (EDC) compounds, such as bisphenol A (BPA). Evidence suggests that this EDC acts on receptor binding sites of various hormones (e.g., estrogen and progesterone) interfering the hormonal response. The aim of this study is to evaluate the cell types in mammary gland reactive stroma of senile female gerbils (Meriones unguiculatus) exposed to BPA during gestation and lactation, as well as the expression and quantification of vascular endothelial growth factors (VEGF) and fibroblast growth factors (FGF-10). In this regard, three experimental groups of animals will be used and subjected to daily gavage with: water, oil and 50 µg/kg/day of BPA. Immunohistochemistry will be employed to growth factors expression, activated fibroblasts, CD34+ cells and fibroblasts. For the identification of telocytes and myofibroblasts, as well as a more specific labeling of activated fibroblasts, double labeling with antibodies will be performed with immunofluorescence. The VEGF and FGF-10 growth factors will also be quantified using the Western Blotting technique. In this way, it will be possible to better understand the functioning of the mammary gland during senescence and the impacts caused on the mammary stroma exposure to BPA in hormone sensitivity windows.