Inhibition of Glycosphingolipid Biosynthesis Does Not Impair Growth or Morphogenesis of the Postimplantation Mouse Embryo

Abstract: Whole embryo culture (WEC) of organogenesis-stage mouse embryos was adapted for glycosphingolipid (GSL) metabolic studies to evaluate the hypothesis that de novo GSL biosynthesis is a prerequisite for growth and morphogenesis of the early postimplantation embryo. WEC supports the growth and development of postimplantation mouse embryos to stages that are indistinguishable from those achieved in vivo. N -Butyldeoxygalactonojirimycin ( N B-DGJ) is an N -alkylated imino sugar that specifically inhibits biosynthesis of all glucosylceramide-based GSLs. N B-DGJ inhibited glucosylceramide and lactosylceramide biosynthesis nearly completely and inhibited ganglioside biosynthesis ～90% in both the embryo and visceral yolk sac. N B-DGJ also significantly reduced total ganglioside content in both the embryo and visceral yolk sac as estimated by the cholera toxin immunooverlay technique. A shift in expression from the structurally simple to the structurally complex gangliosides was also observed in N B-DGJ-treated embryos and yolk sacs. Despite causing major changes in GSL biosynthesis and composition, N B-DGJ had no effect on embryo viability, growth, or morphology. The findings suggest that de novo GSL biosynthesis may not be a prerequisite for the growth and morphogenesis of the organogenesis-stage mouse embryo.