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FEBS Lett. 2006 May 15;580(11):2803-7. Epub 2006 Apr 21.

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

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Neural Development Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EA, UK.


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.

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