Grantee Research Project Results
Final Report: Liver and the Metabolic Syndrome
EPA Grant Number: R834594C001Subproject: this is subproject number 001 , 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: Liver and the Metabolic Syndrome
Investigators: Gruppuso, Phillip
Institution: Rhode Island Hospital
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:
The original goals of this project were to develop a model in which human fetal liver is transplanted into nude rats. We intended to demonstrate that manipulation of the host environment in the adult rat xenograft recipients will induce changes in fetal liver, then go on to characterize the effect of host arsenic exposure, rapamycin administration and dietary restriction on the xenograft epigenome. However, the goals changed significantly by the end of the second year of the project, by which time we had concluded that the fetal liver transplantation model had not succeeded. At that point, we transferred our efforts to the xenotransplantation of human fetal white adipose tissue (WAT).
Summary/Accomplishments (Outputs/Outcomes):
Conclusions:
Despite an extensive effort and multiple transplant trials in various immunodeficient rodent hosts, human fetal liver xenotransplants consistently led to a rapid loss of hepatocytes and the selective development within the xenografts of maturing biliary duct structures. Since the goal of Research Project 1 was to study toxicant- induced metabolic syndrome, institutional funds were used to explore xenotransplantation of human fetal adipose tissue as a model to study adipogenesis and obesogens. This approach has been successful, and has led Dr. Gruppuso to seek independent R01 funding to support a research program focused on human adipogenesis and the molecular response to the potential obesogens.
Supplemental Keywords:
In utero exposure, mammalian, metals, bisphenol A, perinatal programming, bioavailability, exposure assessment, biochemical research, intrauterine exposure, developmental effects, perinatal exposure, children's health, biological pathways, Health, Scientific Discipline, ENVIRONMENTAL MANAGEMENT, Health Risk Assessment, Risk Assessments, Biology, Risk Assessment, biological pathways, children's health, fetal exposure, bioavailability, developmental effects, perinatal exposure, biochemical researchProgress and Final Reports:
Original AbstractMain 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
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.