Maternal diabetes has an adverse influence on the intrauterine growth of the fetus, which is attributable to the exposure of mammalian embryo to an abnormal metabolic environment. A sustained exposure of the fetus to such an environment, i.e., elevated concentration of glucose, during the first 6-8 weeks of gestation in man, may result in diabetic embryopathy, that is characterized by a multitude of congenital birth defects, including those of the nervous, cardiovascular, skeletal and urogenital systems. The urogenital abnormalities may be associated with caudal regression syndrome or may occur alone in the form of partial or total renal agenesis. Similarly, an increase in the incidence of morphogenetic defects is observed in offsprings of streptozotocin-induced diabetic rats and mice and also in non-obese diabetic mice. In their embryos, an increased expression of laminin and fibronectin, altered mitochondrial morphology of the neuroectodermal cells, altered phosphotyrosine phosphatase and insulin growth factor-1 receptor tyrosine kinase activities and perturbed metabolism of myo-inositol have been observed. For further delineation of the mechanisms involved in the pathogenesis of diabetic embryopathy, the investigators utilized whole embryo culture systems, and found that glucose as well as mannose can induce teratogenic effects. The elevated levels of glucose or its epimer, mannose, in the medium or substitution with diabetic serum results in the depletion of cellular pools of myoinositol, deficiency of arachidonic acid metabolites, an increase in the expression of fibronectin and increased frequency of DNA mutations. The embryonic malformations were reduced when the culture medium was supplemented with myo-inositol, or prostaglandins or scavengers of free oxygen radicals, e.g., superoxide dismutase and catalase. Collectively, these observations indicate a multifactorial basis for the pathogenesis of diabetic embryopathy, and perhaps oxidant stress as the common denominator. As to the effects of hyperglycemia or high concentrations of aldohexoses on a given individual organ system, e.g., on the embryonic metanephros, the information available in the literature is rather limited.