Pathogenesis of retinoic acid-induced ear malformations in a primate model

Citation
X. Wei et al., Pathogenesis of retinoic acid-induced ear malformations in a primate model, TERATOLOGY, 60(2), 1999, pp. 83-92
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
TERATOLOGY
ISSN journal
0040-3709 → ACNP
Volume
60
Issue
2
Year of publication
1999
Pages
83 - 92
Database
ISI
SICI code
0040-3709(199908)60:2<83:PORAEM>2.0.ZU;2-4
Abstract
13-cis retinoic acid (RA) is a causative agent for human/monkey retinoic ac id embryopathy (RAE), in which the most common type of malformation is micr otia or anotia. In the present study, malformed ears of monkey fetuses expo sed to RA during early embryogenesis were analyzed and revealed a subtype o f defects., i.e., apparent duplication of the external/middle ear. A part o f the posterior auricle appeared to be ectopically formed in the anterior a uricular region or in the region posterior to the auricle. Additionally, th ere was duplication of the zygomatic arch, malleus, and incus. In order to characterize possible pathogenetic events underlying these malformations, e mbryos at selected stages were collected after dosing dams with RA at 5 mg/ kg/day during gestational days 12-27. Cellular retinoic acid binding protei n I whole-mount immunostaining showed that RA induced specific alterations in the migration of cranial neural crest cells (NCC). NCC en route to the s econd pharyngeal arch were bifurcated, and some of these NCC migrated abnor mally into the first and/or third arches, which may underlie external ear d uplication. Scanning electron microscopy and neurofilament immunostaining p rovided evidence that there was partial duplication of trigeminal nerve/gan glion following RA insult. The duplication of NCC neuronal derivatives in t he first pharyngeal arch is consistent with duplication of NCC mesenchymal components (zygomatic arch, malleus, and incus). Therefore, RA-induced alte rations in cranial NCC migration patterns are likely to be a pathogenetic e vent underlying ear malformations (including duplication) of RAE in monkeys . (C) 1999 Wiley-Liss, Inc.