Effect of hyperglycemia on sorbitol and myo-inositol content of cultured rat conceptus: failure of aldose reductase inhibitors to modify myo-inositol depletion and dysmorphogenesis.

Growth retardation and dysmorphogenesis were seen in the rat conceptus following culture from day 9.5 to 11.5 of development in the presence of increased amounts of glucose. Sorbitol accumulated in the conceptus during the hyperglycemia whereas total protein, DNA, and free myo-inositol decreased. Similar glucose-related compositional changes were present in separated embryos and extra-embryonic membranes suggesting that all portions of the conceptus participate in the alterations. The aldose reductase inhibitors Sorbinil and Statil obtunded the rises in sorbitol but did not modify the increased incidence of malformations and the fall in DNA, protein and myo-inositol. Thus, the aldose reductase pathway may function in the early post-implantation rat conceptus but the resultant accumulation of sorbitol does not appear to contribute to the growth-retarding, dysmorphogenic, and myo-inositol-depleting effects of hyperglycemia.