Related Experiment Videos
Cranio-facial dysmorphism: experimental study in the mouse, clinical applications
R Glineur1, S Louryan, A Lemaître
1Service de Chirurgie Maxillo-Faciale, Cliniques Universitaires, Hôpital Erasme, Brussels, Belgium.
Abstract:
To obtain a better understanding of mandibulo-facial dysostosis and hemicraniofacial microsomia in man, the authors carried out a histologic and scanning electron microscope study of the facial malformations produced in mouse embryos by retinoic acid and methyl-triazene. The administration of 400 mg/kg 13 cis-retinoic acid (RA) to pregnant C57BL mice on day 9 of gestation produced anomalies of the cephalic extremity in the embryos resembling human mandibulo-facial dysostosis. The 64 embryos collected presented hypoplasia of the branchial arches or the snout in 79% of cases, auricular anomalies in 47% and ophthalmic anomalies in 12.5%. Fourteen NMRI mice on day 10.5 of gestation were treated with 1.5 mg (0.5 mg/kg) methyl-triazene (Methyl). The 126 embryos collected had developed a very high percentage of micromandibles and anomalies of both embryonic ears (94.6% to 100%). Finally, although the facial anomalies produced by retinoic acid resemble the human mandibulo-facial dysostosis syndrome, no correlation was found between hemicraniofacial microsomia and the administration of methyl-triazene.
Insights
Retinoic acid (RA) exposure in mice caused facial defects similar to human mandibulo-facial dysostosis. Methyl-triazene (Methyl) induced severe jaw and ear anomalies, but no link to hemicraniofacial microsomia was found.
Area of Science:
- Developmental Biology
- Teratology
- Craniofacial Biology
Background:
- Mandibulo-facial dysostosis and hemicraniofacial microsomia are complex human congenital conditions.
- Understanding the etiology of these conditions is crucial for diagnosis and treatment.
Purpose of the Study:
- To investigate the teratogenic effects of retinoic acid (RA) and methyl-triazene (Methyl) on craniofacial development in mouse embryos.
- To compare induced malformations with human mandibulo-facial dysostosis and hemicraniofacial microsomia.
Main Methods:
- Histologic and scanning electron microscope analysis of mouse embryos exposed to RA or Methyl during gestation.
- Dose-dependent administration of 13 cis-retinoic acid (400 mg/kg) on day 9.
- Administration of methyl-triazene (1.5 mg) on day 10.5.
Main Results:
- Retinoic acid exposure resulted in anomalies resembling human mandibulo-facial dysostosis, including branchial arch hypoplasia (79%), auricular anomalies (47%), and ophthalmic anomalies (12.5%).
- Methyl-triazene induced significant micromandibles and ear anomalies (94.6%-100%) in embryos.
- No correlation was established between methyl-triazene administration and hemicraniofacial microsomia.
Conclusions:
- Retinoic acid is a potent teratogen causing craniofacial malformations similar to mandibulo-facial dysostosis in mice.
- Methyl-triazene induces distinct craniofacial defects, primarily affecting the mandible and ears, but is not linked to hemicraniofacial microsomia.
- This study provides insights into the developmental pathways of craniofacial anomalies and potential etiological factors.