Developmental toxicity of concanavalin A in rats: association with restricted migration of neural crest cells.
Concanavalin A (Con A), a plant lectin, was injected iv into pregnant rats as a single dose of 5, 10 or 20 mg/kg on gestational day (GD) 8, to investigate developmental toxicity in foetuses at term and to examine histologically embryos between GD 10 and 12. There were high incidences of various malformations in the 10 and 20 mg/kg groups: externally, craniofacial dysplasia and closure defects of the ventral body wall; internally, anophthalmia and cardiovascular malformations; and in the skeleton, anomalies of the anterior region of the vertebrae and ribs. Histological examination revealed that neural crest cells (NCC) in the control embryos appeared to be streaming from the neural crest towards the ventral region on GD 10, 11 and 12, and reached the region of the branchial arches on GD 12. By contrast, those in the Con A-treated embryos were aggregated near the dorsal region on GD 10 and 11, and had not reached the destination even on GD 12. These findings suggest that pathogenesis of developmental toxicity of Con A in rats is associated with disturbance of NCC migration and inhibition of their pluripotentiality at the destination.
Nishida
A
A
Safety Research Laboratory, Tanabe Seiyaku Co Ltd, Osaka, Japan.
Kobayashi
T
T
Ariyuki
F
F
D000014:Abnormalities, Drug-Induced; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000002:abnormalities / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D003208:Concanavalin A / Q000633:toxicity*; D019465:Craniofacial Abnormalities / Q000139:chemically induced; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005865:Gestational Age; D006330:Heart Defects, Congenital / Q000139:chemically induced; D008297:Male; D009432:Neural Crest / Q000166:cytology / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D003208:Concanavalin A