Yolk sac failure in embryopathy due to hyperglycemia: horseradish peroxidase uptake in the assessment of yolk sac function.

We described previously the morphologic alterations of the visceral endodermal yolk sac cells of rat conceptuses cultured under hyperglycemic conditions which occurred concomitantly with major embryonic malformations. To determine whether the transport function of the yolk sac was impaired simultaneously as a result of these hyperglycemic conditions, horseradish peroxidase was used as a tracer protein to assess the transport function of the visceral endodermal yolk sac cells of conceptuses cultured in both control and hyperglycemic media. Cellular uptake of peroxidase, which was added to the culture medium for 3 or 24 hours, was observed in controls. This differed from the marked diminution in peroxidase uptake seen in conceptuses cultured in hyperglycemic medium. These results demonstrate that during hyperglycemia-induced embryopathy, there is concomitant yolk sac failure evidenced by morphologic alterations and impaired endocytosis. These findings therefore strengthen our hypothesis that diabetes-related malformations, as demonstrated experimentally in rat conceptuses, are associated with impairment in the structure and functions of the visceral yolk sac cells during a critical period of organogenesis.