Pathogenesis of encephaloschisis in retinoic-acid-treated hamster embryos I: a morphometric study of the craniofacial structures.

The severity of the developmental disorders of the paraxial mesoderm and neuroectoderm must objectively be compared to determine which of the two structures is more deeply involved in the pathogenesis of encephaloschisis. In the present study, hamster fetuses were obtained from dams that had been treated with retinoic acid, and divided into two groups: fetuses with encephaloschisis and those without apparent external malformations in the cranium and face. Mid-sagittal serial sections of the head were prepared, histologically processed, and utilized for the reconstruction of the profile of the head structures. Using this reconstructed profile, we measured the length of the skull base bone structures (basisphenoid and basiocciput), which develop from the paraxial mesoderm, brain structures (mesencephalon and metencephalon), which develop from the neuroectoderm, and facial bone structures (nasal septum and hard palate), which develop from cephalic neural crest cells. The measured length of each structure was compared between the treated and control groups. It was found that treatment with retinoic acid resulted in significantly (P < 0.05) shortened lengths of the skull base bone structures both in fetuses with encephaloschisis and those without apparent external malformations in the cranium and face. In the brain structure of fetuses without encephaloschisis, as well as in the facial bone structures, however, this shortness was not observed. These results suggest that developmental disorders in the paraxial mesoderm may play an important role in the pathogenesis of encephaloschisis.