Effect of retinoic acid upon the chick embryonic morphogenetic systems. I. The embryotoxicity dose range.

The effects of all-trans-beta-retinoic acid upon the developing chick embryo were investigated using the Chick Embryotoxicity Screening Test (CHEST). A dose of 0.3 microgram, injected subgerminally in stages HH 10--11, arrested the neural tube development, disturbed extraembryonic vasculogenesis, and induced formation of haemorrhagic blisters in the caudal region. Single administration of retinoic acid on days 2, 3, and 4 revealed a stage-specific effect. Being high, due to the abundant mortality of embryos injected on day 2, the effect drops conspicuously on day 3, and rises once again on day 4 when a remarkable proportion of the surviving fetuses suffer from serious morphological damage comprising cardiovascular lesions, maldevelopment of the central face, and dysmelia. The target tissues are similar to those of vitamin A in developing mammals. The increased sensitivity of chick embryo morphogenetic systems between days 3 and 4 supports the hypothesis that the deleterious action of retinoic acid is due to the development of specific binding sites in the target cell populations.