Effects of Alcohol on Gene Expression & Epigenetics of Progeny

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DESCRIPTION (provided by applicant): Alcoholism and alcohol-related illness affect multitudes of American families at a significant financial impact on annual medical and caregiver costs. Furthermore, it is recognized and publicized that chronic alcohol consumption during gestation produces a variety of adverse pregnancy outcomes and birth defects. Yet, the influence of acute alcohol consumption near the time of conception is relatively unknown. Around this early developmental stage, the epigenetic marks, which govern gene expression, are initially established along the genome for all mammals, from mice to humans. Consequently, the oocyte-to-embryo transition is a critical period of development because the totipotent embryo gives rise to the entire individual and any 'epigenetic misprints' occurring during this stage are inherited throughout the body. For instance, some maternal diets at this time change the epigenetic status for specific genes of the mouse embryo, impacting both coat color and metabolism of the offspring. Therefore, the maternal environment may influence the phenotype of the progeny in adulthood. Accordingly, alcohol exposure, even at low amounts, at this critical developmental period may adversely affect the health of offspring later in life. The results from my studies suggest that mice specifically exposed to ethyl alcohol during in vitro maturation of oocytes have a higher incidence of metabolic disease, such as obesity and diabetes in adulthood. As a starting point to understand this phenomenon, alterations in gene expression and methylation status induced by alcohol exposure will be assessed in oocytes and pre-implantation embryos. This study is innovative in that the acute alcohol exposure will be precisely controlled during this developmental stage by using in vitro maturation and in vitro fertilization techniques. This permits investigation of the impacts of alcohol on the egg and early embryo, which sets the stage for abnormal phenotype of the adult offspring. These experiments will help to identify and characterize the epigenetic mechanisms that are established and influenced within the early maternal and embryonic environment, which may predispose individuals to metabolic disease, such as obesity and diabetes.