Relationship between hormonal imbalances and proliferative lesions in the prostate of rats exposed to an environmentally relevant mixture of phthalates

• Grant number: 24/20520-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2025
• End date: January 31, 2026
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Cristiane Figueiredo Pinho
• Grantee: Lívia Centofanti Cózaro
• Host Institution: Faculdade de Ciências (FC). Universidade Estadual Paulista (UNESP). Campus de Bauru. Bauru , SP, Brazil

Abstract

The increasing use of plastic materials in society has raised significant concerns regarding the health impacts associated with their chemical components. Among them, phthalates, stand out for their potential effects as endocrine disruptors. Exposure to these plasticizers, particularly during critical developmental periods, may negatively influence the formation and homeostasis of various reproductive organs, leading to significant tissue alterations, including an increased risk of prostate cancer. In this context, the present study aims to evaluate whether perinatal exposure to an environmentally relevant mixture of phthalates is capable of altering the structure of the rat prostate, focusing on tissue molecular markers involved in the processes of hormonal modulation and cell proliferation. For this, pregnant Sprague-Dawley rats will be treated with a mixture of six different phthalates (Bis(2-ethylhexyl) phthalate, Diethyl phthalate, Di-n-butyl phthalate, Diisobutyl phthalate, Butylbenzyl phthalate and Diisononyl phthalate) from gestational day 12 to postnatal day 21, by daily gavage, at doses of 0µg, 20µg, 200µg and 200mg/kg. On postnatal day 120, the offspring will be euthanized and the dorsolateral prostate of each male will be removed, weighed and processed histologically for morphometric, stereological and histopathological analyses, in addition to immunohistochemistry to evaluate AR (androgen receptor), ER-¿, ER-¿ (estrogen receptors), and Ki67 (cell proliferation) proteins.