Experimental Neural Tube Defect Induced with Hypervitaminosis A in the Rat

Abstract

The causes of human neural defect (NTD) are not clarified yet and there is a multitude of theories on the morphogenesis of this malformation. This experiment was carried out to develop a model for NTD in animal and elucidate the morphogenesis of NTD with particular emphasis on the relationship between exencephaly and anencephaly. With exposure to 150,000 IU of vitamin A on various periods of gestation, ranging from the 7th to the 10th days, not only NTDs but a variety of other systemic malformations such as anophthalmia, exophthalmia, anotia, maxillary and/or mandibular hypoplasia, tail and/or genital agenesis, anal atresia and limb defects were produced. Occurrence of these malformations was more related to the time of exposure than the dose of vitamin A, i. e. NTD could be induced only with exposure on the 8th and 9th days of gestation. It was also possible to mention that the critical period of ex-/anencephaly is the 8th day of gestation and that of spina bifida the 9th day in rats. In addition to the teratogenicity 150,000 IU of vitamin A caused marked increase in fetal mortality and growth retardation if administered before the IOth day of gestation. Observations of the degenerative changes and necrosis in the exencephalic brains in variable extent made it possible to conclude that the classical anencephalic features result from the spontaneous necrosis of the exencephalic malformation.