Genotoxicity and diabetic embryopathy: Impaired expression of developmental control genes as a cause of defective morphogenesis

Since the advent of insulin therapy for diabetes mellitus, the survival of mothers with diabetes prior to pergnancy and their offspring has greatly im proved. Nevertheless, the observation that the earliest stages of organogen esis can be! impaired in the offspring of women with diabetes raises the qu estion of how abnormal fuel metabolism disturbs embryogenesis. Research int o this process has been made possible in recent years by advances in molecu lar biology which makes it possible to study gene expression in early embry os, and by the availability of genetically engineered mutant mouse strains. Using these approaches, a model is emerging in which elevated glucose, by disturbing expression of genes which regulate embryonic development and cel l cycle progression, causes premature cell death of emerging organ structur es, thereby causing defective morphogenesis. Investigation into the signali ng mechanisms by which excess glucose metabolism exhibits toxic effects on embryo gene expression will explain how diabetic embryopathy occurs on a mo lecular and cellular level, as well as increase our understanding of the ro le of metabolic homeostasis in proper embryonic development.