A comparison between trisomy 12 and vitamin A induced exencephaly and associated malformations in the mouse embryo

Summary

Morphological and morphometric comparison of exencephaly in 13–15 day old mouse embryos caused either by chromosomal trisomy (Ts 12) or the teratogenic action of Vitamin A disclosed significant similarities as well as distinct differences: similarities included an open cranial vault and laterally everted brain, shortening of the sagittal and transversal axis of the skull base, caudal shift of the optic axis, deformation and dislocation of the hypophysis and inner ear due to a change of growth vectors of the skull base and its surrounding tissue. The differences were that in Ts 12 the caudal shift of the eyes causes enophthalmia, while after Vitamin A application additional malformations of the facial bones and defective formation of the orbits result in exophthalmia; the inner ear shows developmental retardation and hypoplasia only in Ts 12, but severe impairment of the development of all parts of the ear with complete lack of the outer and middle ear characterizes Vitamin A damage. Similarly, marked inhibition of hypophyseal development, the residues of Rathke's pouch, and cleft of the basal sphenoid occurs after Vitamin A, but is absent in Ts 12.

The differences in the exencephalic malformation complex suggest that the area affected in early organogenesis which determins the later malformation, is limited to the paraxial mesoderm in Ts 12, whereas Vitamin A treatment produces additional head mesenchyme abnormalities, in particular of neural crest derivatives. Although Vitamin A-damaged embryos show more extensive malformations, Ts 12 embryos have a shorter lifespan. This is a consequence of the fact that all the cells of the embryo are endowed with the abnormal chromosomal condition.