Glycosphingolipids are enriched in the cellular plasma membrane and are thought to play a vital role in normal mammalian embryogenesis. The major objective of the proposed research is to characterize the effects of ethanol on glycosphingolipid metabolism in gastrulation and organogenesis stage mouse embryos grown in culture. The researcher's hypothesis is that ethanol interacts with the enzymes responsible for glycosphingolipid metabolism to produce qualitative or quantitative alterations in glycosphingolipid distribution within the early mammalian embryo: these changes perturb the normal developmental program at the cellular level and may contribute significantly to the pathophysiology seen in fetal alcohol syndrome. Whole embryo culture (WEC) of postimplantation mouse embryos is a model developmental system which permits exposure of the presomite stage and early somite stage embryos to known concentrations of ethanol without the complicating issue of maternal influences.
The specific aims are: 1.) To determine the qualitative and quantitative distribution of radiolabeled glycosphingolipids synthesized in gastrulation and organogenesis stage embryos cultured in the presence or absence of ethanol and 2.) To assay the appropriate anabolic/catabolic enzymes of ethanol treated embryos and controls to identify the potential biochemical cause(s) of the altered glycosphingolipid distribution. These studies could establish the foundation for experiments to test rational therapies for the protection of gastrulation and organogenesis stage embryos from ethanol induced alterations in glycosphingolipid biosynthesis.
