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Abstract

In previous experiments excess vitamin A, administered to pregnant rats during the early stages of gestation, was found to interfere with the mitotic activity of the neuro-epithelial cells bordering the neural groove. The result was exencephaly and anencephaly in a high percentage of the newborn. The present work was undertaken to examine the influence of hypervitaminosis A on the behavior of the neuro-epithelial cells of the cerebral hemisphere and the subsequent migration and differentiation of the neuroblasts during the later stages of development.

Swiss-Webster mice were treated with large doses of vitamin A on days 14 and 15 of gestation. When subsequently the cell cycle of the neuro-epithelial cells lining the lateral ventricle of 15-day fetuses was determined, vitamin A was found to increase both the duration of the mitosis and DNA synthetic period. In comparison with the controls, the total generation time was prolonged by approximately 40%. Since almost all neuroblasts of the cerebral cortex originate in the neuro-epithelial zone bordering the lateral ventricle, the total number of neuroblast formed is in all probability less than normal. Indeed, prelimiinary data on the number of cells present in the cerebral cortex of 10-day postnatal rats treated with excess vitamin A toward the end of pregnancy showed a decrease in cell density, indicating either a reduction in the number of cells formed or a degeneration of existing cells.

In a second experiment Swiss-Webster mice were treated with excess vitamin A during three successive days in the second half of pregnancy. The cerebral cortex of the newborn was examined one to ten days after birth. Histological examination revealed a rather sharply delineated zone of abnormal cells characterized by a lightly stained cytoplasm, a thick nuclear memberane, a desely stained nucleoplasm and several dark chromatin bodies. When the position of the zone containing the abnormal cells was analyzed and correlated with the day of formation in the neuroepithelial zone, it was found that the affected cells were neuroblasts already present in the cortex before the vitamin treatment was started. This indicates that excess vitamin A, given to pregnant mice during the later stages of gestation, influences the development of the cerebral cortex, not only by interfering with the production of cells in the neuroepithelial zone, but also by affecting the differentiation of existing neuroblasts. As a result of these anomalies, some of the newborn appeared to have abnormal patterns of behavior.