Morphogenesis of axial skeletal (dysraphic) disorders induced by aliphatic nitriles.

The previous study (Willhite et al., '81) linked the administration of acrylonitrile or propionitrile in the pregnant hamster to the production of severe axial skeletal (dysraphic) malformations in the hamster fetus. The present investigation dealt with histological study of both early embryos and term fetuses challenged with a teratogenic dose of either of these nitriles. Inspection of hamster embryos 10 hours after the teratogenic stimulus revealed mesodermal changes including a reduced number of cells, shrinkage of the cell cytoplasm, and enlarged extracellular spaces. In addition, a reduced number of mitotic figures and focal necrobiosis were noted. The affected embryos were smaller and were delayed in their development as compared to controls. Analysis of the fourteen-day-old hamster fetuses revealed the basichondrocranium in both cranioschisis occulta with encephalocoele and cranioschisis aperta with exencephyaly to be shorter than control and lordotic to the vertebral axis. These alterations were more accentuated in cranioschisis aperta than in cranioschisis occulta. The ultimate skeletal malformations may be the reflection of a primary paraxial mesodermal insufficiency.