The role of hepatic ornithine transcarbamylase deficiency in the orotic aciduria of pregnant mice.

Groups of normal and heterozygote sparse-fur (spf) mutant mice were studied at various stages of gestation, to assess the effects of normal pregnancy on orotate excretion, hepatic mitochondrial urea cycle enzymes and any predisposition to the development of fatty liver. Results show a higher total daily excretion of urinary orotate by normal pregnant mice on the 8th and 15th days of gestation, which came to within the usual basal range of excretion of non-pregnant mutant heterozygotes with hereditary ornithine transcarbamylase deficiency. Liver ornithine transcarbamylase and carbamyl phosphate synthetase-I activities were reduced in pregnant mice on the 16th day of gestation (P less than 0.05). No fatty change, bile stasis or glycogen depletion was discernible on optical microscopy in normal or mutant mice. Nonspecific changes were seen on ultrastructural examination. Orotic aciduria seen in pregnant mice may be directly related to a physiological deficiency of liver ornithine transcarbamylase. However, the depletion of both the mitochondrial urea cycle enzymes, seen on the 16th day of pregnancy, may be indicative of a metabolic stress at the mitochondrial level.