Title: Epigenetics, environmental exposure, and reproduction in the Collaborative Cross PI/PD: David L. Aylor The proposed research is a systems genetics approach to characterize the complex relationships between genetic variation, epigenetic regulation, gene expression, male reproductive physiology, and environmental exposure. To accomplish this goal, we will leverage the power of diverse inbred mouse strains and the Collaborative Cross, a mouse reference population that has ideal properties for systems genetics. To identify gene-by-environment (G?E) interactions, we will perturb the reproductive system with the powerful estrogen diethylstilbestrol (DES) and phenotype identical exposed and control populations. We will measure DNA methylation, mRNA expression, and reproductive traits with the purpose of modeling genetic effects and G?E across three levels of genome function. This research will produce new biological knowledge of the genetic networks underlying the reproductive system, DES function at the molecular level, and genes underlying DES sensitivity.

Public Health Relevance

Endocrine disrupting chemicals (EDCs) are used in many consumer products and most people are exposed to low levels of EDCs regularly. Mice have been used to show how EDC exposure can cause adverse effects on the reproductive system, but the mice used in these studies are usually genetically identical. Since we know genetics are an important determinant of sensitivity to environmental exposures in humans, we propose to study EDC effects on reproduction in a newly available mouse resource that has a human-like amount of genetic variation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Transition Award (R00)
Project #
4R00ES021535-03
Application #
8831815
Study Section
Special Emphasis Panel (NSS)
Program Officer
Mcallister, Kimberly A
Project Start
2014-06-17
Project End
2017-05-31
Budget Start
2014-06-17
Budget End
2015-05-31
Support Year
3
Fiscal Year
2014
Total Cost
$249,000
Indirect Cost
$77,333
Name
North Carolina State University Raleigh
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
042092122
City
Raleigh
State
NC
Country
United States
Zip Code
27695