The Mechanism of Vitamin a Induced Teratogenesis.

IT IS generally recognized that some congenital malformations may be caused by an abnormal environment surrounding the mother in pregnancy. Many experiments have been reported concerning the teratogenesis due to various hypovitaminoses, but there are relatively few reports on teratogenesis resulting from the administration of a large quantity of vitamin. Among the latter, the best known are malformations caused by hypervitaminoses A and D. In spite of many experiments on the effect of hypervitaminosis A carried out by Cohlan(1953,1954,1961), Giroud & Martinet (1955,1956,1957,1959,1960), Millen & Woollam (1957a, 19576, 1958a, 19586, 1958c, 1961), Kalter & Warkany (1961), Hartel & Hartel (1960), and also by many Japanese workers (Inaba, 1958; Nakamura, 1958; Araki, 1958; Yukioka, 1958; Tsuruhara, 1959; Kuzukawa, 1960), the mechanism of such a teratogenesis still remains obscure. Cohlan (1954) and Giroud (1957) considered a direct action of vitamin A on the foetus, because vitamin A content in the liver of the foetus was markedly increased when the former was given in excessive dose to the mother in pregnancy. Takekoshi (1961a, 19616) observed that cortisone, trypan blue, urethane and chondroitin sulfate enhanced the teratogenic activity of vitamin A, and that the adrenal weight of animals given a large dose of vitamin A was increased, while the lipid droplets of the adrenal cortex became minute in size and increased in number. From these facts, he concluded that excessive production of adrenal cortical hormone in these cases might not be negligible as compared to the direct action of vitamin A on the foetus. It may be easily assumed that the intimate reciprocal actions between various hormones and vitamins are necessary for the normal development of foetuses. Therefore, in the present study, special attention was paid to thyroid function in animals which were given a large amount of vitamin A, and the relationship