The Honeybee Syndrome — Implications of the Teratogenicity of Mannose in Rat-Embryo Culture

Abstract

Lethal effects of D-mannose in the honeybee have been recognized for more than half a century. We observed another toxic effect of D-mannose during culture of rat embryos from the early head-fold stage to the 26–to-29-somite stage (Days 9Vz through 111/2 of gestation). The addition to culture mediums of 1.5 mg of D-mannose per milliliter caused growth retardation and faulty neural-tube closure in approximately two thirds of the embryos. Mannose effects occurred during the first 24 hours of culture and were attended by modest inhibition of the glycolysis that constitutes the principal energy pathway at this stage of development. Adding more glucose to preserve glycolytic flux or increasing atmospheric oxygen to promote oxidative metabolism offset the mannose teratogenesis. Our findings highlight the metabolic vulnerabilities that exist during early organogenesis, before oxidative flexibility is established. They may serve as a model to explain the teratogenicity of many other seemingly unrelated agents that could act by perturbing glycolysis at this vulnerable stage. (N Engl J Med 1984; 310:223–30.)