The 1986 McCollum award lecture. Fuel-mediated teratogenesis during early organogenesis: the effects of increased concentrations of glucose, ketones, or somatomedin inhibitor during rat embryo culture.

Whole rat embryos were explanted at head-fold, late pre-somite stage (day 9.5 of gestation) and cultured in rat sera varyingly supplemented with glucose (3, 6, 9, or 12 mg/mL), D,L sodium beta-hydroxybutyrate (2, 4, 8, or 16 mM), or both (6 mg/mL D-glucose plus 8 mM beta-hydroxybutyrate). During 48 h culture, increasing glucose alone or beta-hydroxybutyrate alone effected growth retardation and faulty neural and extraneural organogenesis in dose-dependent fashion. Synergistic dysmorphogenic effects occurred when minimally teratogenic concentrations of glucose and beta-hydroxybutyrate were combined. Sera from diabetic animals containing somatomedin inhibitor bioactivity were also able to produce growth retardation and major developmental lesions in presence of amounts of glucose and ketones which of themselves were not teratogenic. Thus, aberrant fuels and fuel-related products can impair growth and organogenesis in early post-implantation embryo. Such fuel-mediated teratogenesis may be multifactorial and include possibilities for synergistic and additive interactions.