Effect of Hypervitaminosis a on the Fetus of Several Species of Rodents, With Special Reference to Malformation of the Extremities

Abstract

Since a teratogenic effect of excess viamin A on the rat fetus was first reported by Cohlan in 1953, many investigators have confirmed and expanded his results (Giroud and Martinet 1955, 1956, 1958 Woollam 1957, 1963;Baba and Araki 1959;Deuschle et al. 1959;Kalter 1960;Kalter and Warkany 1961;Woollam and Millen 1961;Murakami et al. 1963Murakami et al. , 1965Takekoshi 1964;Ohzu and Shoji 1965). They have described the occurrence of various types of anomalies such as gross malformations which are associated with the central nervous system, a certain combination of defects called the anomalous oculodentofacial pattern by Deuschle et al. (1959), cleft palate, micromelia and other malformations of the limb, digital anomalies, anal atresia, and malformations of vertebrae and ribs as well as some visceral changes mainly in rodents.Parallel experiments by the same investigator using more than two species of laboratory animals however, are few except for a brief report by Giroud and Martinet (1958). It is difficult to discuss difference in teratogenic action of hypervitaminosis A among species on the basis of the results previously published by different investigators, because of differences in the strain of animals, time and route of administration and the form and dosage of vitamin A as well as in the object of observation in each study. To discuss difference in the teratogenic effect of an extrinsic agent among species, not only constancy of the factors which may influence upon the teratogenic action of the agent (Wilson 1959, Fraser 1963 but also parallel experiments done by the same investigator under the same technical level during the same period is required. From this viewpoint parallel experiments on hypervitaminosis A were carried out in mice, rats and rabbits in the present investigation.Numerous malformations of the same type previously described in the literature were found. In carrying out the present study, special attention was paid to differences in the occurrence of limb and digital malformations among species and the following relationships were examined.