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Increased accumulation of sorbitol in offspring of manifest diabetic rats
Insights
Maternal diabetes increases embryo defects, even with aldose reductase inhibitor treatment. While the inhibitor reduced sorbitol accumulation in embryos, it did not prevent developmental issues in this rat model.
Area of Science:
- Reproductive biology
- Developmental biology
- Endocrinology
Background:
- Maternal diabetes poses risks to embryo-fetal development.
- The polyol pathway and sorbitol accumulation are implicated in diabetic complications.
Purpose of the Study:
- To investigate the impact of maternal diabetes on somatic development and polyol pathway activity during gestation in rats.
- To assess the efficacy of an aldose reductase inhibitor in mitigating these effects.
Main Methods:
- A rat model of diabetic pregnancy was used.
- Offspring were evaluated for growth, mortality, and malformations.
- Sorbitol levels in embryos, membranes, fetal livers, and placentas were measured.
- Aldose reductase inhibitor treatment was administered to diabetic rats.
Main Results:
- Diabetic rats showed increased embryo-fetal resorptions and malformations, irrespective of aldose reductase inhibitor treatment.
- Sorbitol levels were elevated in embryos and membranes during early gestation and in fetal livers and placentas during late gestation in diabetic rats.
- The aldose reductase inhibitor normalized embryonic sorbitol levels and partially reduced it in fetal livers and placentas.
- No correlation was found between sorbitol levels and malformations within the diabetic groups.
Conclusions:
- Enhanced polyol metabolism and sorbitol accumulation occur in embryos of diabetic mothers during organogenesis.
- Sorbitol accumulation is likely not the primary cause of developmental disturbances in early diabetic pregnancy.
Abstract:
The effects of maternal diabetes on somatic development and activity of the polyol pathway were investigated during early and late gestation in a rat model for diabetic pregnancy. We studied embryo-fetal growth, mortality, and malformation rate in the offspring of nondiabetic rats and in the offspring of diabetic rats either treated with an aldose reductase inhibitor during gestation or left untreated. The numbers of embryo-fetal resorptions and malformations were significantly increased in the diabetic groups compared with the controls despite maternal treatment with the aldose reductase inhibitor. The sorbitol content of embryos and membranes from the diabetic rats in early gestation was increased 3-5 times over the control values. Similarly, elevated sorbitol levels were observed in the fetal livers and placentas of the diabetic rats in late gestation. Administration of the aldose reductase inhibitor to the pregnant diabetic rats normalized the sorbitol levels in the embryos and their membranes, whereas the sorbitol contents of the fetal livers and placentas were significantly lowered but not completely corrected. Furthermore, in the diabetic groups, no differences in sorbitol levels could be demonstrated between malformed and nonmalformed offspring. The results of this study suggest that enhanced polyol metabolism leading to increased sorbitol accumulation is present in the embryos of diabetic mothers as early as organogenesis. This accumulation is apparently not a major factor in the early developmental disturbances (e.g., growth perturbations and congenital malformations) of diabetic pregnancy.