Grantee Research Project Results
2012 Progress Report: The Mechanisms of Endocrine Disruptors in Laboratory Mice
EPA Grant Number: R834509C003Subproject: this is subproject number 003 , established and managed by the Center Director under grant R834509
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Water Environment and Reuse Foundation's National Center for Resource Recovery and Nutrient Management
Center Director: Olabode, Lola
Title: The Mechanisms of Endocrine Disruptors in Laboratory Mice
Investigators: Perera, Frederica P. , Miller, Rachel L. , Champagne, Frances
Current Investigators: Champagne, Frances , Miller, Rachel L.
Institution: Columbia University in the City of New York
EPA Project Officer: Callan, Richard
Project Period: September 24, 2009 through September 23, 2014 (Extended to September 23, 2015)
Project Period Covered by this Report: August 1, 2011 through July 31,2012
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
(1) Examine the consequence of prenatal oral Bisphenol A (BPA) exposure on neurobehavioral, obesity and immune dysfunction in Balb/c mice by determining whether prenatal BPA exposure is associated with abnormal brain cytoarchitecture, impaired social, anxiety-like and cognitive performance, greater adult body weight, body fat composition and organ fat, and immune dysfunction in the adult offspring or grandoffspring.
(2) Examine the consequence of prenatal oral BPA exposure for tissue-specific molecular modifications in mice by determining prenatal BPA exposure-induced changes in DNA methylation in genes sensitive to endocrine disruption and immune dysregulation in the brain (hippocampus, hypothalamus, cortex), adipocytes and blood of the prenatally BPA exposed offspring and grandoffspring at gestation day 19 and adulthood (postnatal day [PND]60).
(3) Examine the consequence of prenatal inhaled polycyclic aromatic hydrocarbon (PAH) exposure at current levels determined to exist in New York City’s Northern Manhattan/South Bronx on neurodevelopment and obesity in Balb/c mice by determining whether prenatal PAH exposure is associated with abnormal brain cytoarchitecture, impaired anxiety-like and cognitive performance, greater body weight through weaning to adulthood, body fat composition and organ fat content in adult offspring and grand offspring.
(4) Examine the consequence of prenatal inhaled PAH exposure for tissue-specific molecular modifications (DNA methylation) in mice of genes sensitive to endocrine disruption and immune dysregulation in the brain, adipocytes and blood of the prenatally exposed offspring and grandoffspring at gestation day 19 and PND60.
Progress Summary:
Cohorts of Balb/c mice have been exposed prenatally to low dose BPA (2 μg/kg, 20 μg/kg, 200 μg/kg or tocopherol-stripped corn oil control). In addition, we optimized the experimental exposure of PAHs to pregnant mice. We have submitted our findings to the Proceedings of the National Academy of Sciences.
Cohorts of Balb/c mice (n = 80) have been exposed prenatally to PAH vs control air, mated and used in experiments to address aims 3 and 4. Analyses are continuing. DNA methylation analysis for all genes is ongoing.
Future Activities:
BPA (aims 1,2): Analysis of the effect of postnatal maternal behavior on all BPA-associated effects (neurobiological and behavioral) is ongoing. Planned experiments include analysis of ER protein levels in the brain, analysis of post-weaning growth trajectories, additional behavioral analysis, assessment of fetal brain and placenta gene expression/DNA methylation, and completion of assessment of target genes. Correspondence between blood/spleen/brain gene expression and DNA methylation will be determined.
PAH (aims 3,4): In the next period, additional mice from multiple batches of PAH exposure will be used to complete the above observations. Brain cytoarchitecture in the hypothalamus, hippocampus and cortex in the adult offspring will be examined histologically. Plus, a few females per treatment group (negative control and PAH exposed) will be mated with adult Balb/c males to test for effects on the F2 generation. Methylation experiments will have been started. Experiments studying high methyl donor diets are planned.
Journal Articles on this Report : 4 Displayed | Download in RIS Format
Other subproject views: | All 21 publications | 9 publications in selected types | All 7 journal articles |
---|---|---|---|
Other center views: | All 104 publications | 62 publications in selected types | All 60 journal articles |
Type | Citation | ||
---|---|---|---|
|
Kundakovic M, Champagne FA. Epigenetic perspective on the developmental effects of bisphenol A. Brain, Behavior, and Immunity 2011;25(6):1084-1093. |
R834509 (2011) R834509 (2012) R834509 (2013) R834509 (2014) R834509 (Final) R834509C003 (2012) R834509C003 (Final) |
Exit Exit Exit |
|
Lovinsky-Desir S, Miller RL. Epigenetics, asthma, and allergic diseases:a review of latest advancements. Current Allergy and Asthma Reports 2012;12(3):211-220. |
R834509 (2012) R834509 (2013) R834509 (Final) R834509C003 (2012) R834509C003 (Final) |
Exit |
|
Rauh VA, Horton MK, Miller RL, Whyatt RM, Perera F. Neonatology and the environment:impact of early exposure to airborne environmental toxicants on infant and child neurodevelopment. Neoreviews 2010;11(7):363-369. |
R834509 (2011) R834509 (2012) R834509 (2013) R834509 (2014) R834509 (Final) R834509C002 (Final) R834509C003 (2012) R834509C003 (Final) |
Exit Exit |
|
Witherspoon NO, Trousdale K, Bearer CF, Miller RL. The public health and policy implications of epigenetics and pediatric health research. Environmental Health Perspectives 2012;120(10):a380-a381. |
R834509 (2012) R834509 (2013) R834509C003 (2012) |
|
Supplemental Keywords:
Bisphenol A, BPA, polycyclic aromatic hydrocarbons, PAHs, mice, obesity, neurodevelopment, children , RFA, Health, Scientific Discipline, INTERNATIONAL COOPERATION, ENVIRONMENTAL MANAGEMENT, POLLUTANTS/TOXICS, Chemicals, Biochemistry, Children's Health, Environmental Policy, Biology, Risk Assessment, air toxics, developmental neurotoxicity, air pollution, childhood obesity, endocrine disruptors, assessment of exposure, children's vulnerablity, children's environmental health, growth & developmentRelevant Websites:
Columbia Center for Children’s Environmental Health Exit
Progress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R834509 Water Environment and Reuse Foundation's National Center for Resource Recovery and Nutrient Management Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834509C001 The Role of Endocrine Disruptors in Childhood Obesity
R834509C002 The Role of Endocrine Disruptors in Neurodevelopmental Disorders
R834509C003 The Mechanisms of Endocrine Disruptors in Laboratory Mice
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.
Project Research Results
7 journal articles for this subproject
Main Center: R834509
104 publications for this center
60 journal articles for this center