Effect of vitamin A on development of the central nervous system

Abstract

Pregnant rats and mice were treated with large doses of vitamin A to examine its effect on the closure of the neural groove in the developing embryo. In the rat the most effective dose was 30,000 U.S.P. units given at day 8, 9, and 10 of pregnancy. Twenty‐six per cent of the implanted embryos showed anencephaly and/or myeloschisis. In the mouse the results of vitamin A treatment were inconsistent.In 12‐day rat embryos, the lateral walls of the diencephalon and mesencephalon were slightly everted. Mitotic neuro‐epithelial cells were frequently piled up two or three rows thick, causing a disruption of the internal limiting membrane. Many cells were characterized by a bleb‐like cytoplasmic evagination protruding into the lumen.During the following days, the everted walls of the diencephalon and mesencephalon expanded farther and farther over the sides of the head, thereby often covering the lateral hemispheres and the eyes. Although the hemispheres were displaced by the everted diencephalic plates and the eyes were frequently buried deep inside the head, histological differentiation proceeded normally and a primitive cerebral cortex as well as normal eye structures were observed. The accumulation of mitotic figures, the formation of cytoplasmic protrusions, and the presence of small neuro‐epithelial rosettes throughout the brain were the most striking cytological anomalies.By the eighteenth day of development, small hemorrhages occurred in the mesenchyme surrounding the brain and degeneration became apparent. At birth a small amount of degenerated brain tissue was all that remained from the large exencephalic brain, and the newborn had the appearance of an anencephalic. It is concluded that large doses of vitamin A prevent the neural groove from closing, possibly by interfering with the Cell membrane and/or the mitotic activity of the neuro‐epithelial cells.