BIOTIN INFLUENCES PALATAL DEVELOPMENT OF MOUSE EMBRYOS IN ORGAN-CULTURE

Maternal biotin deficiency is strongly teratogenic in CD-1 mice. The m ost common malformations are craniofacial and limb defects such as cle ft palate, micrognathia and micromelia. The effect of biotin deficienc y on palatal development in mouse embryos on d 12 of gestation was stu died by culturing mouse embryonic palates in serum-free medium using a suspension culture system. In control embryos palatal processes devel oped to the fused stage after 72 h in culture. The fusion of palatal p rocesses was further increased by the addition of biotin (10(-8) mol/L ) to the medium. The addition of organic acids such as propionic, beta -methyl crotonic or beta-hydroxy isovaleric acids as well as avidin to the medium did not affect the stage of palatal formation. Cycloheximi de completely blocked the fusion of palatal shelves. In embryos from b iotin-deficient mice, the incidence of fusion between the palatal shel ves was <7% and increased to >30% when biotin (10(-8)-10(-6) mol/L) wa s added to the medium. The addition of fatty acids to the organ cultur e medium did not have any effect on the fusion of palatal processes. T he incorporation of S-35-methionine into protein from biotin-deficient embryo explants was 88% of that in controls. The results indicate tha t biotin deficiency may interfere directly with synthesis of specific proteins and the formation of palatal processes.