Biotin deficiency affects the proliferation of human embryonic palatal mesenchymal cells in culture

J Nutr. 2008 Apr;138(4):680-4. doi: 10.1093/jn/138.4.680.


It has recently been demonstrated that pregnancy in women may cause mild biotin deficiency without any clinical signs. However, the teratogenicity of biotin deficiency in humans has not been well investigated. On the other hand, our previous studies have shown that maternal biotin deficiency induces many kinds of malformations, such as cleft palate, micrognathia, and micromelia, in all animal fetuses. However the mechanism for cleft palate induction under biotin-deficient conditions is unknown. Therefore, to investigate the possible mechanisms for cleft palate induction in embryos, we investigated the effects of biotin deficiency on human embryonic palatal mesenchymal (HEPM) cells in culture in this study. HEPM cells were cultured in biotin-deficient and biotin-physiological (control) media for 5 wk. The proliferative availabilities of HEPM cells in the biotin-deficient state were significantly lower after wk 2 of culture (41.3% of the control). Biotin concentrations in biotin-deficient cells were drastically lower after wk 1 of culture, whereas those in the control cells remained at almost the same level. Biotinidase activities were also lower in biotin-deficient cells. Holocarboxylases in biotin-deficient cells were fewer after the first week of culture and were almost undetectable after wk 2. The amount of biotinylated histones in the nuclei of biotin-deficient cells was lower than in the control cells. This suppressed proliferation of mesenchymal cells may delay or inhibit the growth of palatal processes in embryos and thus it may partially contribute to the mechanisms for cleft palate induction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biotin / deficiency*
  • Biotin / pharmacology*
  • Biotinidase / metabolism
  • Biotinylation
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Histones / metabolism
  • Humans
  • Mesoderm / cytology*
  • Palate / cytology*
  • Palate / embryology*
  • Vitamins / pharmacology


  • Histones
  • Vitamins
  • Biotin
  • Biotinidase