Effects of hyperglycaemia on sorbitol and myo-inositol contents of cultured embryos: treatment with aldose reductase inhibitor and myo-inositol supplementation.

To demonstrate the myo-inositol depletion hypothesis in hyperglycaemia-induced embryopathy, rat conceptuses of 9.5 days of gestation in the early head-fold stage were grown in vitro during neural tube formation for 48 h with increasing amounts of glucose. The effects of an aldose reductase inhibitor and the myo-inositol supplementation were also investigated. Sorbitol and myo-inositol contents were measured in separated embryos and extra-embryonic membranes including yolk sac and amnion at the end of culture. After addition of 33.3 mmol/l and 66.7 mmol/l glucose to the culture media, the myo-inositol content of the embryos was significantly decreased by 43.1% (p less than 0.05) and 64.6% (p less than 0.01) of the control group, while a marked accumulation of sorbitol was observed (25 and 41 times that of the control). Although the addition of an aldose reductase inhibitor (0.7 mmol/l) to the hyperglycaemic culture media containing an additional 66.7 mmol/l glucose significantly reduced the sorbitol content of embryos to approximately one-eighth, the myo-inositol content of embryos remained decreased and the frequency of neural lesions was unchanged (23.1% vs 23.9%, NS). Supplementation of the myo-inositol (0.28 mmol/l) completely restored the myo-inositol content of the embryos and resulted in a significant decrease in the frequency of neural lesions (7.1% vs 23.9%, p less than 0.01) and a significant increase in crown-rump length and somite numbers. Much less significantly, sorbitol accumulation was also observed in the extra-embryonic membrane in response to hyperglycaemia, neither hyperglycaemia nor the myo-inositol supplementation modified the myo-inositol contents of the extra-embryonic membrane.(ABSTRACT TRUNCATED AT 250 WORDS)