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Protection of mice from teratogen-induced cleft palate by exogenous methionine
1Center for Craniofacial Molecular Biology, School of Dentistry, University of Southern California, Los Angeles 90033, USA.
Abstract:
A 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 exogenous methionine in cleft palate reduction, that will provide a biological rationale for considering methionine as a therapeutic agent.
Insights
Methionine can significantly reduce or prevent craniofacial abnormalities, like cleft palate, caused by toxicants such as retinoic acid and glucocorticoids during embryonic development.
Area of Science:
- Developmental biology
- Toxicology
- Teratology
Background:
- Congenital craniofacial abnormalities pose a significant challenge in biomedical research.
- Extrinsic toxicants like retinoic acids and glucocorticoids can induce these abnormalities during embryonic development.
Purpose of the Study:
- To investigate the potential of methionine in reducing or preventing toxicant-induced craniofacial abnormalities, specifically cleft palate.
- To evaluate the efficacy of methionine as a therapeutic agent against teratogenic effects.
Main Methods:
- Studies were conducted using a genetically susceptible B10.A mouse strain.
- Pregnant mice were administered toxicants (all-trans retinoic acid or triamcinolone) followed by methionine.
- Methionine was administered via a single intraperitoneal (IP) dose at 187 mg/kg on embryonic day 13 (E13) at 21 hours.
Main Results:
- Subsequent administration of methionine largely reduced or completely rescued the teratogenic effects of retinoic acid and glucocorticoids.
- The greatest reduction in secondary cleft palate frequency was observed with methionine treatment.
- No detrimental toxic effects were observed in mice treated with the therapeutic level of methionine.
Conclusions:
- Methionine shows promise as a therapeutic agent for reducing toxicant-induced cleft palate.
- Further research is warranted to explore the biological rationale for methionine's protective effects.
- Findings support considering methionine for the prevention of congenital craniofacial abnormalities.