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, the investigators 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 (GXE) interactions, the investigators will perturb the reproductive system with the powerful estrogen diethylstilbestrol (DES) and phenotype identical exposed and control populations. The investigators will measure DNA methylation, mRNA expression, and reproductive traits with the purpose of modeling genetic effects and GXE 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 the investigators know genetics are an important determinant of sensitivity to environmental exposures in humans, they propose to study EDC effects on reproduction in a newly available mouse resource that has a human-like amount of genetic variation.

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 the investigators know genetics are an important determinant of sensitivity to environmental exposures in humans, they 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
Career Transition Award (K99)
Project #
5K99ES021535-02
Application #
8478110
Study Section
Special Emphasis Panel (ZES1-LKB-D (D))
Program Officer
Shreffler, Carol K
Project Start
2012-06-01
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
2
Fiscal Year
2013
Total Cost
$87,921
Indirect Cost
$6,513
Name
University of North Carolina Chapel Hill
Department
Genetics
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Rutledge, Holly; Aylor, David L; Carpenter, Danielle E et al. (2014) Genetic regulation of Zfp30, CXCL1, and neutrophilic inflammation in murine lung. Genetics 198:735-45