Abstract
Biotin is a water soluble vitamin which serves as a covalently bound coenzyme for various types of carboxylase and is involved in fatty acid synthesis, glucose and amino acid metabolism. Biotin is well distributed in various kinds of foods. Overt biotin deficiency rarely occurs spontaneously in animals. Clinical signs characteristic of biotin deficiency, such as dermatitis and alopecia, develop in humans and rodents. In the series of our studies, the importance of biotin for normal reproduction and the development of embryos and offspring was demonstrated in mammals and birds. Maternal baltin deficiency during gestation produces external malformations such as cleft palate, micromelia and micrognathia in mice. However, there are species and strain differences in the teratogenic effects of biotin deficiency. The effects of biotin deficiency on palatal development in mouse embryos were studied by culturing embryonic palates and palatal mesenchymal cells. The incidence of palatal fusion was increased to 30% when 10^<-8>M-10^<-6>M biotin was added to the medium. In the biotin-deficient state, the proliferative availability of mesenchymal cells was significantly lower after 2 weeks of culturing. The amount of biotinylated histories in the nuclei was also lower than in the control cells. Protein expression in adenosine diphosphate (ADP)-ribosylation factor 2 and α-crystallin may be down-regulated in the mesenchyme of the palatal processes.As for the bioavailability of biotin during gestation, a large amount of biotin was transported to palates and mandibles on dg 12-15 (day of gestation). However, the biotin excretion in urine decreased after dg 6 and the urinary concentration of 3-hydroxyisovaleric acid increased after dg 12. The requirement of biotin increased during gestation and embryonic development, resulting in a lack of biotin in dams. On the other hand, excessive biotin intake during gestation induced many kinds of external malformations such as micrognathia, micromelia and edema in mouse fetuses. Also spermatogenesis was blocked by the excessive biotin intake for the long term in growing male rats. In birds, biotin was supplied in large amounts to growing ovarian follicles, particularly just before ovulation. In the embryos, free biotin in the yolk increased shortly after fertilization. A large amount of free biotin was incorporated into the embryo at the age of the 3-4 day (day 3-4). The expression of biotin-dependent carboxylase was different in egg yolk and embryos. Acetyl-CoA carboxylase (ACC) activity increased in the egg yolk after day 2 and pyruvate carboxylase (PC) increased with the growth of the embryos. Also biotinidase activity showed its highest value on day 2. Thus, biotin supply to the embryo differed among embryonic growth stages and organs, suggesting its involvement in the formation of each tissue and organ. From our findings, it is apparent that biotin is an essential nutrient and plays a critical role in the embryonic development of mammals and birds, indicating that it is important to maintain proper biotin levels during gestation.
