The worldwide epidemic of obesity and diabetes presents a formidable challenge because of the serious complications of these disorders. Maternal obesity and diabetes are associated with infant growth abnormalities, both small-for-gestational age and large-for-gestational age, and subsequent increased risk of obesity, diabetes and metabolic syndrome in the offspring. The mechanisms underlying this increased risk in offspring are not well understood, but likely involve both genetic and environmental effects that influence pre andpost-implantation biology. This interdisciplinary initiative will test the hypothesis that the metabolic milieu during pregnancy contributes to the risk of obesity, diabetes, and cardiovascular disease in offspring, independent of genetic influences. In addition we will attempt to pinpoint the vulnerable period in development at which the metabolic milieu plays a role in long-term outcome of the fetus. Genetic mouse models of obesity and diabetes will be used as recipients of blastocyst transfer of control embryos to characterize the timing and magnitude of these phenomena. The specific aim is to determine whether maternal obesity and diabetes predispose to the development of metabolic syndrome in offspring. This work will provide important insights into the epigenetic influences of the intrauterine environment on metabolic and cardiovascular diseases in offspring of obese and diabetic mothers. Moreover, these studies will lay the groundwork for investigation to understand the mediators of intrauterine environmental influences and the mechanisms through which they result in metabolic imprinting.