The Effects of Alcohol on the Regulation of Imprinted Genes in Mouse Embryonic Stem Cells

Abstract

Our environment plays a critical role on our growth and development. In recent years epigenetics has captured the interest of many researchers. Epigenetics looks at how environmental factors affect the genetic material during development. One increasingly common disorder is Fetal Alcohol Spectrum Disorder or FASD. FASD is seen in many infants that have been exposed to alcohol, an environmental toxin, during fetal development. This disorder causes distinct mental and physical abnormalities whose origin comes from alternations to the molecular mechanisms controlling development. In this study, we examined how gene regulation is affected when alcohol is introduced into the environment by looking at genomic imprints. Genomic imprinting is the unique programming of genes that exclusively activate the expression of either the maternal or paternal copy of a gene. A change in the specific expression pattern found in these genes signifies an error in epigenetic programming.

By looking at embryonic stem (ES) cells derived from F1 crosses between the C57BL/6 and Mus musculus castaneus strains of mice, we have identified the expression of five imprinted genes. The following five genes: Ube3a, Peg3, H19, Igf2r, and Igf2 were examined in ES cells treated with three different alcohol concentrations to mimic typical consumptions found in today’s society. We have found that three out of the five genes show an up regulation in the maternal imprinting pattern at the 95% confidence interval. These results suggest that alcohol does affect the expression of some imprinted genes and aids in the understanding of the observed clinical phenotypes and the role of epigenetics in the etiology of FASD.