Excess methionine suppresses the methylation cycle and inhibits neural tube closure in mouse embryos

FEBS Lett. 2006 May 15;580(11):2803-7. doi: 10.1016/j.febslet.2006.04.020. Epub 2006 Apr 21.


Suppression of one-carbon metabolism or insufficient methionine intake are suggested to increase risk of neural tube defects (NTD). Here, exogenous methionine unexpectedly caused frequent NTD in cultured mouse embryos. NTD were associated with reduced cranial mesenchyme cell density, which may result from a preceding reduction in proliferation. The abundance ratio of S-adenosylmethionine to S-adenosylhomocysteine was also decreased in treated embryos, suggesting methylation reactions may be suppressed. Such an effect is potentially causative as NTD were also observed when DNA methylation was specifically inhibited. Thus, reduced cranial mesenchyme density and impairment of critical methylation reactions may contribute to development of methionine-induced NTD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azacitidine / pharmacology
  • Embryo Culture Techniques
  • Embryo, Mammalian / drug effects*
  • Embryo, Mammalian / embryology*
  • Embryo, Mammalian / metabolism
  • Embryo, Mammalian / pathology
  • Folic Acid / pharmacology
  • Methionine / pharmacology*
  • Methylation / drug effects
  • Mice
  • Neural Tube Defects / chemically induced*
  • Neural Tube Defects / embryology*
  • Neural Tube Defects / metabolism
  • Neural Tube Defects / prevention & control
  • Phenotype


  • Folic Acid
  • Methionine
  • Azacitidine