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.