PROTECTION OF MICE FROM TERATOGEN-INDUCED CLEFT PALATE BY EXOGENOUS METHIONINE

AbstractA major challenge for biomedical research is the reduction and/or prevention of congenital craniofacial abnormalities which can be induced by some extrinsic toxicants such as retinoic acids (e.g. isotretinoin, Accutane®) and glucocorticoids (corticosteroid hormones) during embryonic craniofacial morphogenesis. Our present studies using a genetically susceptible mouse strain (B10.A) indicate that the teratogenic actions of exogenous retinoic acid or glucocorticoid in secondary cleft palate induction can be largely reduced or even completely rescued by subsequent administration of methionine. The greatest reduction in frequency of all-trans retinoic acid- or triamcinolone-induced secondary cleft palate was obtained by a single-dose IP administration of methionine at 187 mg/kg to pregnant mice on E13 21 hr. It appears that detrimental toxic effects were not observed in mice treated with this therapeutic level of methionine. Our present findings support the need for further research into the role of e...