The ultrastructural effects of excess maternal vitamin A on the primitive streak stage rat embryo

1. A single injection of 1 i.u. vitamin A palmitate was administered to pregnant female rats on one of the days 0–14 of pregnancy. The litters were examined for malformations and prenatal death. On the basis of the results of this preliminary investigation, treatment on day 8 was selected for detailed study. 2. Day-8 embryos were examined with the electron microscope from 2 to 24 h after maternal vitamin A administration. Ultrastructural abnormalities were: membrane swelling (cytoplasmic vacuoles, ‘budding’, nuclear membrane irregularities, general swelling leading to cell death); changes in the extra- to intracellular fluid ratio; increase in the number of lipid droplets; autophagic vacuoles; condensed and swollen mitochondria. 3. These changes were not equally distributed among the different cell types. It is suggested that this differential effect leads to a loss of synchrony between the development of structures from the different germ layers, in addition to a general retardation. Loss of contact between mesoderm cells may delay normal migratory movements and induction of neural plate. The general retardation is related to the lower birthweights of treated embryos versus controls, and the differential effects to the subsequent abnormal morphogenesis.