Vincristine‐Induced Craniofacial Skeletal Teratogenicity in Foetal Rabbits: Multimodal Morphometric Assessment and Partial Protection by L‐Carnitine

Abstract

Vincristine, a microtubule-disrupting vinca alkaloid, is teratogenic during organogenesis and may compromise neural crest-related craniofacial development; however, its effects on craniofacial and cervical development and the potential for maternal L-carnitine protection remain unclear. Pregnant New Zealand White rabbits (n = 9) were allocated to Group I-Control (saline), Group II-Vincristine (0.1 mg/kg intraperitoneally [IP] on gestational day [GD] 10) and Group III-Vincristine + L-carnitine (vincristine 0.1 mg/kg IP on GD 10 plus L-carnitine 500 mg/kg IP on GD 9-14). Foetuses were collected at GD 29 for craniofacial and cervical morphometry, radiographic measurements and Alcian blue/Alizarin red S skeletal staining. Compared with Group I controls, vincristine caused 36.7% embryonic resorption, universal craniofacial malformations, severe intrauterine growth retardation, 33%-85% reductions in craniofacial dimensions relative to control values, 29%-48% decreases in radiographic skull and mandibular measures and 22.8%-57.5% shortening of cervical metrics (all p < 0.001). With L-carnitine co-administration, resorption decreased to 13.3% and gross malformation burden was reduced; quantitatively, L-carnitine recovered approximately 53%-78% of the vincristine-induced craniofacial deficit, 65%-100% of the radiographic skull and mandibular deficit and 71.5%-79% of the cervical shortening, although all measurements except rostral skull width remained significantly different from controls (p < 0.05). These findings indicate that maternal L-carnitine provides substantial, but incomplete, attenuation of vincristine-associated craniofacial and cervical teratogenicity in the rabbit model.