Abstract
1. ICR-JCL mice were treated with an intraperitoneal injection of 600,000 IU/kg of vitamin A on day 10 of pregnancy, and divided into two groups. 2. In the first group, fetuses were removed and examined for external malformations on day 18 of pregnancy. All of the fetuses of vitamin A-treated mice showed micromelia, oligodactylia or syndactylia. 3. In the second group, the limb buds of the embryos were dissected out at 2, 4, 12, 24, 48 and 72 hours after the injection of vitamin A and were submitted to histological observations. 3-a. The first sign of the effect of hypervitaminosis A on the limb buds was found at 24 hours after the administration of vitamin A as an increase in the number of necrotic mesenchymal cells in the pre- and postaxial areas of the limb buds. 3-b. At 48 hours after the administration of vitamin A, the mesenchymal necrosis reached its maximum in the vitamine A-treated limb buds. 3-c. At 72 hours after the administration of vitamin A, digital rays and mesenchymal condensations were not recognized in the region corresponding to the first and second digits in the treated limb buds. 4. From these findings, it was concluded that the limb anomalies observed on day 18 of pregnancy were mainly due to the massive mesenchymal necrosis which was caused by hypervitaminosis A in the earlier phase of limb development.
