Inhibition of collagen cross-linking associated with β-aminopropionitrile-induced cleft palate in the rat

Abstract

Lathyrogenic compounds have been shown previously to induce cleft palate in the rat when administered during gestation. The present study examines the induction of cleft palate by the lathyrogen, β-aminopropionitrile (BAPN) and attempts to correlate this with the effect BAPN has on the cross-linking of embryonic collagen. It was found that 98% cleft palate fetuses could be produced by a single oral dose of 600 mg/kg BAPN only when administered during a 24-hr period of gestation beginning with day 15, whereas cleft palate was not induced on day 14 or 16. BAPN did not affect the synthesis of sulfated mucopolysaccharides or proteins, including collagen, in the embryo, but a dramatic and reversible inhibition was observed in collagen cross-linking. Maximum inhibition occurred 24 hr after BAPN administration, whereas no effect was seen after 48 hr. A correlation was observed between the inhibition of collagen cross-linking and cleft palate formation when BAPN was given in various concentrations as a single oral dose on day 15. It is suggested that the inhibition of collagen cross-linking in the embryo may play a role in cleft palate induction by BAPN.