The incidence of marginal
biotin deficiency in normal human gestation is approximately one in three. In ICR mice, maternal
biotin deficiency results in
cleft palate,
micrognathia,
microglossia and limb hypoplasia. However, the relationships among the severity of maternal
biotin deficiency, fetal
biotin status and malformations have not been reported. This study utilized validated indices of
biotin status to investigate the relationships among maternal
biotin status, fetal
biotin status and the rate of
fetal malformations in ICR mice.
Biotin status was controlled by feeding diets with varying egg white concentration. In dams and fetuses,
biotin status was assessed by hepatic
biotin content and hepatic activity of the
biotin-dependent
enzyme propionyl-CoA carboxylase; in dams, status was also assessed by urinary excretion of
biotin and
3-hydroxyisovaleric acid. Malformations were assessed morphologically.
Biotin was measured by HPLC/
avidin-binding assay.
Propionyl-CoA carboxylase (PCC) activity was determined by H(14)CO(3) incorporation.
3-Hydroxyisovaleric acid concentration was determined by GC/MS. Although no overt signs of deficiency appeared, metabolic disturbances caused by
biotin deficiency were detectable in dams and fetuses. These disturbances increased with increasing egg white. Fetal
biotin status correlated significantly with maternal
biotin status (fetal vs. dam hepatic
biotin, r = 0.671; fetal vs. dam PCC activity, r = 0.70). The incidences of malformations were strikingly dependent on egg white concentration. We conclude that in ICR mice, marginal maternal
biotin deficiency causes fetal
biotin deficiency. We speculate that the
fetal malformations are primarily the consequence of fetal
biotin deficiency. Because murine malformations appeared at degrees of
biotin deficiency that are similar to those in human gestation, we speculate that some human
fetal malformations may be caused by
biotin deficiency.