Introduction of late gestational teratogenesis in rat lung by hypervitaminosis A

Long-Evans black-hooded rats treated via stomach tube with 160,000 USP units of retinyl acetate (vitamin A) in 0.5 ml Mazola corn oil on gestational days 15--19 deliver normal-sized litters with significantly decreased viability. Vitamin A is known to effect the differentiation and to stimulate the growth of epithelial cells. Additionally, lung epithelia undergo marked morphologic and physiologic changes late in gestation. Thus the effects of hypervitaminosis A on developing lung constitute an excellent system for the study of teratogenesis late in gestation. Non-hilar, right lower-lobe sections of lungs from the vehicle control and experimental groups, compared via quantitative light microscopy, revealed no significant difference in gross overall histologic appearance on any given day, either in the total number of airways present in the volume of lung sectioned or in the percent area of any individual airway occupied by cells or by lumen. The only significant difference was in the number of cells per square micrometer in that region of an airway occupied by cells. Additionally, there was a significant difference between the control and experimental mitotic indices on gestational days 18 and 19. Thus in the experimental group the number of cells lining the developing airways increases, while the absolute thickness of this cellular layer remains constant. Transmission electron microscopy (TEM) fails to reveal any morphologic differences between control and treated type II pneumatocytes. The increased number of respiratory cells in what otherwise appears to be normal lung may create a diffusion-perfusion imbalance or other difficulties contributing to the heightened neonatal mortality resulting from teratogen exposure late in gestation.