ALTERED MITOCHONDRIAL MORPHOLOGY OF RAT EMBRYOS IN DIABETIC PREGNANCY

Background: Previous studies in vivo and in vitro have suggeted that the oxidative metabolism of the embryo may have a role in the treatogenicity of diabetic pregnancy. In particular, the production of reactive oxygen species by the embroyonic mitochondiria has been implicated in the teratological process. The induction of congenital malformations by the diabetic milieu occurs during the early embryonic development. The present study aimed to estimate the role of the embryonic mitochondria in the teratological process of diabetic pregnancy by studying mitochondrial morphology in the embryos exposed to a diabetic environment in vivo or in vitro during early organogenesis and late fetal development. Methods: For studies in vivo embryos of control or streptozotocin-dia-betic rats were taken at gestational days 9–11 and sujected to light and electron microscopical analysis. The brain, heart, and liver of day-15 fetuses were also observed. For studies in vitro day-9 embryos of normal rats were cultured in a whole-embryo culture system for 48 hours. The culture media were supplied with high conectration of diabetes-related substrates and metabolites, and their effect on structure of embryonic neuropeithelial cells determined. Results: The light microscopoical observations demonstrated numberous cytoplasmic vaculoes in the ectoderm of day-9 embryos and the neuroepithelium and blood cells of day-10 and day-11 embryos of diabetic rats. Ultrastructuraily, these vacuoles were found to be mitochondria undergoing large-amplitude swelling with loss of matrix density and disturbed cristae. In contrast, no Mitochondrial differences were found in the brain, heart, and liver, when day-15 fetuses from normal and diabeic rats were compared. Ultrastructural analysis of day-9 embryos cultured for 48 hours in the presnce of high conectrations of D-Glucose, pyruvate, β-hydroxybutyrate, and α-ketoisocaproate also showed high-amplitude mitochondrial swelling in the neuroepithelium. The motochondrial swelling was, however, not found in embryos cultured in a high conectration of L-glucose, excluding simple osmotic effects of the diabetes-related substrated and metabolites. Conclusions: The mitochondrial morphological changes appeared in embryos subjected to a diabetic environment during a time period when the congenital malformations in diabetic pregnancy are induced. The results support the notion that embryonic mitochondria are involved in the teratological process of diabetic pregnancy. © 1995 Wiley-Liss, inc.