Grantee Research Project Results

Prostate and Endocrine Disruption

EPA Grant Number: R834594C002
Subproject: this is subproject number 002 , established and managed by the Center Director under grant R834594
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Formative Center for the Evaluation of Environmental Impacts on Fetal Development
Center Director: Boekelheide, Kim
Title: Prostate and Endocrine Disruption
Investigators: Boekelheide, Kim
Institution: Brown University , Thanos Scientific Consulting Group , Women & Infants Hospital of Rhode Island
Current Institution: Brown University
EPA Project Officer: Hahn, Intaek
Project Period: December 1, 2009 through November 30, 2012
RFA: Children's Environmental Health and Disease Prevention Research Centers: Formative Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health

Objective:

With an increasing incidence worldwide, prostate adenocarcinoma is the most common non-skin cancer diagnosis and the second leading cause of death in men in the U.S. Estrogenicity during in utero development has been associated with later life risk of prostate adenocarcinoma, raising concern that early life exposures to endocrine disrupting chemicals may be contributing to this disease burden. This pilot project uses the prostate as a model to examine the developmental effects of endocrine disrupting chemicals. Following characterization of the maturation sequence, dysregulation of this developmental sequence by estradiol exposure, with and without a second later exposure, will be determined. Histopathological and biomarker assessment will identify estradiol-induced pre-cancerous alterations in ductal morphogenesis, and the long-term effects of estradiol exposure, including the occurrence of prostatic intraepithelial neoplasia, will be identified. Building on this basic characterization of the model, early developmental exposures to the environmental endocrine disruptors bisphenol A and genistein will be compared with estradiol for epigenetic modifications. The working hypothesis is: Prostate cells respond to estrogenic endocrine disrupting chemical exposure with aberrant differentiation due to altered DNA methylation. Rodents have been useful models for the study of prostate carcinogenesis; however, spontaneous prostate neoplasia in rodents is rare while humans are uniquely susceptible.

Expected Results:

This project offers the very distinct advantages of human relevance and enhanced susceptibility in the evaluation of environmental impacts on prostate development. The goal of this pilot project is to build a platform to evaluate the developmental origins of later life prostate disease associated with endocrine disrupting chemical exposure, focusing on the underlying epigenetic mechanisms that control disease induction and progression.

Publications and Presentations:

Publications have been submitted on this subproject: View all 4 publications for this subproject | View all 13 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 4 journal articles for this subproject | View all 8 journal articles for this center

Supplemental Keywords:

in utero exposure, mammalian, metals, bisphenol A, developmental biology, perinatal programming; environmental management, Scientific Discipline, Health, Risk Assessment, Biology, Risk Assessments, Health Risk Assessment, bioavailability, exposure assessment, biochemical research, intrauterine exposure, developmental effects, perinatal exposure, children's health, biological pathways, Health, Scientific Discipline, ENVIRONMENTAL MANAGEMENT, POLLUTANTS/TOXICS, Health Risk Assessment, Risk Assessments, Biology, Chemicals, Risk Assessment, bioavailability, fetal exposure, perinatal exposure, biological pathways, children's health, developmental effects, endocrine disruptors, biochemical research

Progress and Final Reports:

2010

2011

Final Report

Main Center Abstract and Reports:

R834594 Formative Center for the Evaluation of Environmental Impacts on Fetal Development

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834594C001 Liver and the Metabolic Syndrome
R834594C002 Prostate and Endocrine Disruption
R834594C003 Lung, Arsenic Exposure, and Tissue Remodeling

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.