Eur J Anat, 11 (1): 17-26 (2007)

Histological examination of major craniofacial abnormalities produced in rat foetuses with a variety of retinoids

Wise M., Emmanouil-Nikoloussi E.N., Moxham B.J.

Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3US, United Kingdom; Faculty of Medicine, Aristotle University of Thessaloniki, University Campus, Thessaloniki 54124, Greece; Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3US, United Kingdom

ABSTRACT Retinoic acid is a vitamin-A derived compound that plays an important role in craniofacial development. However, numerous studies have shown that exogenously administered retinoic acid analogues have teratogenic effects both in humans and in experimental animals. This paper presents the results of a study where exogenous administration of retinoic acid analogues to pregnant Wistar rats resulted in major craniofacial malformations of most of the foetuses. Seven groups of pregnant rats were exposed to a variety of retinoic acid analogues, administered in different doses on different gestational days. A further control group was not exposed to these compounds. All the rats were impregnated and sacrificed on the same gestational days (GD 0 and GD 18 respectively). Following examination of the 34 foetuses obtained from the retinoic acid-treated litters, 5 were chosen for histological investigation to describe the major, external craniofacial malformations resulting from exposure to the teratogens. These malformations included exophthalmos, anophthalmos, exencephaly, craniofacial asymmetry and facial tags. Also reported here are the incidences of teratomas and absorptions in these litters. Previously, we have reported the incidence of cleft lip and palate in rats subjected to an identical experimental regimen. Our data provide further evidence that retinoic acid analogues, all-trans-retinoic acid in particular, disturb normal craniofacial development in such a way that a spectrum of craniofacial malformations can be induced by embryonic exposure to these compounds.

Keywords: retinoic acid derivative, retinoid derivative, retinol, animal experiment, animal model, animal tissue, article, cleft lip palate, controlled study, craniofacial malformation, embryo, exencephaly, exophthalmos, female, fetotoxicity, fetus, gestational age, histology, histopathology, nonhuman, pregnancy, rat, teratogenicity, teratoma, Wistar rat