Correlation between alterations in Meckel's cartilage and induction of cleft palate with beta-aminoproprionitrile in the rat.

The lathyrogen beta-aminoproprionitrile (BAPN) induces cleft palate in rats when administered at a critical time in secondary palate formation. BAPN is known to inhibit the crosslinking of newly synthesized collagen, but its primary site of action in producing cleft palate is unknown. In this study time-mated Sprague-Dawley rats were given a single oral dose of 600 mg/kg BAPN at five known gestational ages in the 48 hours before palatal shelf elevation, and the fetuses were studied on days 16, 17 and 18. Evaluation of craniofacial relations and palate development in BAPN-treated heads revealed that delayed palatal shelf elevation and resulting cleft palate were related to retrognathia of the mandible. However, shortening of the mandible was due primarily to vertical and lateral bending of Meckel's cartilage. High and retruded tongue positions that were present with the deformities in Meckel's cartilage interfered with palatal shelf movement to the horizontal plane. The group treated with BAPN at 15 days 7 hours, approximately 24 hours before normal palatal shelf elevation, had the most severe defects in Meckel's cartilage, the longest delay in palatal shelf elevation and the highest incidence of cleft palate. Inhibition of crosslinking of collagen in Meckel's cartilage appeared to weaken the cartilage during the critical period in facial development when extention of the tongue and mandible beneath the primary palate is required to facilitate palatal shelf elevation.