Influence of various levels of hypervitaminosis A and zinc deficiency on teratogenesis and DNA synthesis in the rat

Administration of excess vitamin A during gestation results in gross malformations of the fetus. It has been proposed that the mechanism of action of vitamin A in producing malformations is through a reduction in DNA synthesis and altered cellular differentiation. A similar mechanism has been suggested for the teratogenic effect of zinc deficiency. The simultaneous treatment of pregnant rats with excess vitamin A (3,000 or 30,000 IU/day) and low dietary zinc (0.4 or 9 ppm) resulted in a high incidence of fetal malformations from each treatment with no discernible interaction. Both treatments resulted in brain deformities, but zinc deficiency caused a higher incidence of lung and tail malformations and a general reduction in the uptake of 3 H‐thymidine into embryonic DNA. The administration of excess vitamin A resulted in a higher incidence of fetal eye and palate anomalies than did zinc deficiency but had no effect on DNA synthesis. The lack of interaction between the treatments with regard to fetal malformations, the differences in the types of organs which were affected by the two treatments, and the reduction in DNA synthesis by zinc deficiency but not by vitamin A excess suggest that these conditions alter development through different mechanisms.