Altered energy metabolism is an additional factor contributing to copper (Cu) deficiency-induced teratogenesis

Based on our findings of low SOD activity and high oxidative damage, we have suggested that reductions in oxidant defense represent one mechanism contributing to Cu deficiency-induced teratogenesis. In the current work, we tested the hypothesis that an additional mechanism could be impaired enorgy production as a consequence of Cu deficiency associated reductions in cytochrome c oxidase activity. Embryos were removed at gestation day 10 front dams fed either a control (+Cu) or Cu deficient (-Cu) diet (8.0 μg/g and <0.5 μg/g diet, respectively). The +Cu embryos were explanted into -+Cu sera. (19.2 μM) while -Cu embryos wore cultured in -Cu sera (1.2 μM) for 48 h. Kmbryos removed from -Cu dams and cultured in -Cu sera, had significantly lower cytochrome c oxidase activity (50% reduction) than +Cu embryos cultured in +Cu sera. To determine if the lower cytochrome c oxidase activity was functionally significant, ATP concentrations were determined in single embryos using a chemiluminescence assay. AT P concentrations were significantly lower in embryos from -Cu dams that were cultured in -Cu serum than those removed from +Cu dams that were cultured in +Cu serum. These data support the concept that the teratogenicity of Cu deficiency occurs through a number of mechanisms including impairments in energy production and oxidant detente. The role of Cu deficiency-induced alterations in other processes such as angiogenesis and extracellular matrix maturation needs to be investigated.