Antifungal triazole derivative triadimefon induces ectopic maxillary cartilage by altering the morphogenesis of the first branchial arch.
BACKGROUND
The triazole derivative, triadimefon (FON), induces branchial arch abnormalities in post-implantation rat embryos cultured in vitro, and cranio-facial malformations in mouse fetuses. Ectopic maxillary cartilage has been also described as a typical FON-related malformation. This work studies the morphogenesis of the ectopic cartilage in rat embryos and fetuses exposed in vivo to FON during the early postimplantation period.


METHODS
Pregnant rats were treated with 0, 250, and 500 mg/kg FON on Day 9.5 of pregnancy (D9.5) and sacrificed at term (D20), during the early fetal period (D17) or at different embryogenetic periods (D10, D11, D12). The skeleton was examined after stain of bone and cartilage or of cartilage alone respectively at term or at D17. The neural crest cell (NCC) migration and compaction was investigated at D10 and D11 and the cranial nerve organization described at D12.


RESULTS
Triadimefon is teratogenic in rats under the chosen experimental conditions. The malformations were at the level of the cranio-facial and axial skeleton at term and of the hindbrain nerves in embryos. A NCC abnormal migration and compaction was observed at the level of the first branchial arch: in FON-exposed embryos NCC were detected at the level of both maxillary and mandibular processes, whereas control embryos showed the immunostained tissue only at the level of the mandibular bud.


CONCLUSIONS
The pathogenic pathway, proposed to explain the ectopic cartilage, is the displacement of part of the NCC-derived tissues at the maxillary region of the first branchial arch.
Di Renzo
Francesca
F
University of Milan, Department of Biology, Italy.
Broccia
Maria L
ML
Giavini
Erminio
E
Menegola
Elena
E
D000014:Abnormalities, Drug-Induced; D000818:Animals; D001934:Branchial Region / Q000002:abnormalities*; D002356:Cartilage / Q000002:abnormalities*; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D008297:Male; D008437:Maxilla / Q000002:abnormalities*; D009024:Morphogenesis / Q000187:drug effects; D009432:Neural Crest / Q000166:cytology / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D014230:Triazoles / Q000633:toxicity*
D005659:Fungicides, Industrial; D014230:Triazoles; C032910:triadimefon