{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:09:21Z","timestamp":1791144561846,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2005,6,6]],"date-time":"2005-06-06T00:00:00Z","timestamp":1118016000000},"content-version":"vor","delay-in-days":3870,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Teratology"],"published-print":{"date-parts":[[1994,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mild hyperhomocysteinemia is frequently observed in mothers who gave birth to a child with a neural tube defect (NTD). In a previous study we showed <jats:sc>L<\/jats:sc>\u2010homocysteine was embryotoxic to gestational day 10 (GD 10) rat embryos in culture, however, no NTDs were observed. We therefore investigated the effect of <jats:sc>L<\/jats:sc>\u2010homocysteine on the development of neural plate stage (GD9. 5) rat embryos. Other objectives of this study were investigation into whether the embryotoxicity of <jats:sc>L<\/jats:sc>\u2010homocysteine could be attenuated by compounds related to its metabolism and clarification of the mechanism of <jats:sc>L<\/jats:sc>\u2010homocysteine embryotoxicity. In GD9. 5 rat embryos <jats:sc>L<\/jats:sc>\u2010homocysteine was not toxic at 1\u2010 and 2\u2010mM concentrations. Rather at these concentrations it promoted development of the rat embryos in serum that without supplementation caused NTDs in the embryos. <jats:sc>L<\/jats:sc>\u2010Methionine had the same preventive effect at even lower concentrations, but folinic acid (1mM) did not improve embryonic development. <jats:italic>N<\/jats:italic><jats:sup>5<\/jats:sup>\u2010Methyltetrahydrofolate (5\u2010Ch<jats:sub>3<\/jats:sub>\u2010THF)(100 \u03bc,M)<jats:sc>L<\/jats:sc>\u2010serine(6 mM), and <jats:sc>L<\/jats:sc>\u2010methionine(6 and 12 mM) attenuated the embryotoxicity of <jats:sc>L<\/jats:sc>\u2010homocysteine(6 mM) in GD10 rat embryos. Vitamin B<jats:sub>12<\/jats:sub>(10 \u03bcM) completely abolished the embryotoxicity of <jats:sc>L<\/jats:sc>\u2010homocysteine, which was shown to be mediated by catalysis of the spontaneous oxidation of <jats:sc>L<\/jats:sc>\u2010homocysteine, to the less toxic. <jats:sc>L<\/jats:sc>\u2010homocysteine. In GD 11 rat embryos, both <jats:sc>L<\/jats:sc>\u2010and <jats:sc>D<\/jats:sc>\u2010homocysteine were readily and taken up when added to the culture (3 mM)and increased embryonic S\u2010adenosylhomocysteine (SAH) levels 14\u2010and 3\u2010fold, respectively. This difference was shown to be caused by the stereospecific preference of SAH hydrolase. We propose the basis for <jats:sc>L<\/jats:sc>\u2010homocysteine embryotoxicity is an inhibition of transmethylation reactions by increased embryonic SAH levels. \u00a9 1994 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/tera.1420500506","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T16:06:09Z","timestamp":1118505969000},"page":"348-360","source":"Crossref","is-referenced-by-count":103,"title":["Prevention of neural tube defects by and toxicity of <scp>L<\/scp>\u2010homocysteine in cultured postimplantation rat embryos"],"prefix":"10.1002","volume":"50","author":[{"given":"Leon A. G. J. 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