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.

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.