Morphogenesis of experimental anencephaly

The sequential morphological development of anencephaly was studied in an experimental model. Vitamin A was administered to pregnant rats on gestational days 8, 9, and 10. When the litters were allowed to proceed to term, the treatment resulted in fetuses with anencephalic features. The progressive morphological development of the malformation was then established by histological and gross study of embryos and fetuses of different ages. The earliest lesion identified was a microfocal necrosis located in the head fold epithelium near the anterior neuropore on day 9; it was lateral to the normal position of physiological necrotic foci seen in control embryos. Subsequent to the appearance of the initial lesion, the malformation developed as everted brain folds extending vertically from the diencephalon in the pattern of exencephaly. The neural tube in the region of the malformation never closed, and the exencephaly arose as a progressive development of non-closed neural tube. Finally, the classical anencephalic resulted from the spontaneous necrosis of the exencephalic malformation. This study indicates that anencephaly in an experimental model arises from microscopic foci of necrosis near the anterior neuropore and develops through non-closure of the neural tube.