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 supplementedwith glucose(3, 6, 9, or 12 mg/mL), D,L sodium fl-hydroxybutyrate (2, 4, 8, or 16 mM), or both (6 mg/mL D-glucose plus 8 mM �-hydroxybutyrate). During 48 h culture, increasing glucose alone or �9-hydroxybutyrate alone effected growth retardation and faulty neural and extraneural organogenesis in dose-dependent fashion. Syn- ergistic dysmorphogenic effects occurred when minimally teratogenic concentrations ofglucose and fl-hydroxybutyrate were combined. Sera from diabetic animals containing somatomedin inhibitor bioactivity were alsoable to producegrowth retardation and major developmental lesionsin presence of amounts of glucose and ketones which of themselves were not teratogenic. Thus, aberrant fuels and fuel-related productscan impair growth and organogenesisin early post-implantation embryo. Such fuel-mediated teratogenesis may be multifactorial and include possibilitiesfor synergistic and additive interactions. Am J C/in Nuir 1986;44:986-95.