IMPACTS OF ANDROGEN IMBALANCE ON PROSTATIC HEALTH AND CARCINOGENESIS: A DOHaD PERSPECTIVE ON ENDOCRINE DISRUPTORS

• Grant number: 25/12498-0
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: August 11, 2025
• End date: September 10, 2025
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Sebastião Roberto Taboga
• Grantee: Leonardo Araújo Caires de Aguiar
• Supervisor: Christiani Andrade Amorim
• 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
• Institution abroad: Universitè Catolique de Louvain (UCL), Belgium
• Associated to the scholarship: 23/15425-9 - Impacts of androgen modulation on the male prostate after perinatal exposure to the endocrine disruptor bisphenol A, BP.IC

Abstract

The field of Developmental Origins of Health and Disease (DOHaD) highlights how early-life exposure to environmental pollutants like BPA can predispose individuals to diseases. The prostate, highly sensitive to steroid hormone signaling, is especially vulnerable to endocrine disruption during development, potentially contributing to cancer onset. This project investigates the impact of androgenic imbalance on male and female prostates under endocrine disruption, using gerbils as a model. Two experimental approaches will be carried out in collaboration with UCLouvain. In the first, male gerbils perinatally exposed to BPA are subjected to androgenic modulation (supplementation, deprivation, and blockage) as part of an ongoing project (FAPESP: 2023/15425-9). Preliminary findings suggest increased neoplastic susceptibility associated with changes in androgen receptor isoform expression. In this next phase, in-depth analyses will explore the role of androgenic signaling using multiplex immunofluorescence, Western blotting, and RT-qPCR to assess epigenetic alterations, hormone receptors, cell dynamics, and tissue structure. As for the second task, considering the impact of androgen supplementation observed for the male prostate, the intent is to evaluate the effects of the increase in androgens after an early life insult in females androgen-responsive organs as well. Female offspring, which develop a prostate-like structure in this model, will be analyzed under a control endocrine disruption and conditions with and without androgen supplementation in an induced carcinogenesis scenario. Morphological and molecular analyses will assess the epigenetic and histological impacts of this perinatal insult, focusing on alterations linked to prostate cancer androgen sensibility and responsiveness. These investigations aim to provide new insights into prostate pathogenesis influenced by endocrine disruption in both sexes. (AU)