Some non-genotoxic agents cause epigenetic changes, including aberrant DNA methylation. A subset of these drug, called endocrine disrupters -synthetic chemicals resembling natural hormones-, have profound effects on development and fertility. The central hypothesis of the proposal is that developing germ cells, which undergo genome-wide epigenetic reprogramming, are especially vulnerable to the epigenetic effects of endocrine disrupters. Fetal germ cells provide an excellent study system to reveal the origin of transgenerational epigenetic effects. This proposal seeks to identify epigenetic changes in fetal germ cells after intrauterine exposure to selected endocrine disrupters. To address the central hypothesis, the specific aims are to: 1) Determine the methylation status of the H19/lgf2 imprinting control region (ICR) in perinatal germ cells after fetal exposure to endocrine disrupting chemicals;2) Assess global transcription changes caused by endocrine disrupters in fetal germ cells and gonadal somatic cells;and 3) Identify targets for aberrant hypermethylation by endocrine disrupters, in mouse female and male germ cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES015185-04
Application #
7645030
Study Section
Special Emphasis Panel (ZES1-LWJ-E (EP))
Program Officer
Heindel, Jerrold
Project Start
2006-09-22
Project End
2011-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
4
Fiscal Year
2009
Total Cost
$402,043
Indirect Cost
Name
City of Hope/Beckman Research Institute
Department
Type
DUNS #
027176833
City
Duarte
State
CA
Country
United States
Zip Code
91010
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