Marginal biotin deficiency is teratogenic in mice and perhaps humans: a review of biotin deficiency during human pregnancy and effects of biotin deficiency on gene expression and enzyme activities in mouse dam and fetus.
Recent studies of biotin status during pregnancy provide evidence that a marginal degree of biotin deficiency develops in a substantial proportion of women during normal pregnancy. Several lines of evidence suggest that although the degree of biotin deficiency is not severe enough to produce the classic cutaneous and behavioral manifestations of biotin deficiency, the deficiency is severe enough to produce metabolic derangements in women and may be teratogenic. In studies of mice, a similar degree of biotin deficiency induces characteristic fetal malformations at a high rate. Fetal hepatic biotin content and PCC activity decrease indicating that the fetuses also become biotin deficient. Fetal hepatic acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase and beta-methylcrotonyl-CoA carboxylase abundances determined by Western blotting decreased more than the dam holocarboxylase abundances (10% of sufficient vs. 50% of sufficient); however, hepatic mRNA for the carboxylases and for HCS did not change significantly in either dams or fetuses. These observations suggest that maternal biotin deficiency results in a lack of adequate biotin to biotinylate apocarboxylases in the fetus despite the normal expression of genes coding for the apocarboxylases and holocarboxylase synthetase.
Department of Biochemistry, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. mockdonaldm@uams.edu
Donald M
DM
Mock
D000818:Animals; D001710:Biotin / Q000172:deficiency* / Q000494:pharmacology; D004798:Enzymes / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008099:Liver / Q000196:embryology / Q000378:metabolism; D051379:Mice; D011247:Pregnancy / Q000378:metabolism*; D013723:Teratogens / Q000378:metabolism
D004798:Enzymes; D013723:Teratogens; D001710:Biotin