{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:09:13Z","timestamp":1791050953114,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2007,3,28]],"date-time":"2007-03-28T00:00:00Z","timestamp":1175040000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2007,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>BACKGROUND:<\/jats:bold> Prenatal exposure to ethanol induces holoprosencephalic malformations in both humans and laboratory animals. However, its teratogenic window for inducing holoprosencephaly is narrow, and the teratogenic mechanism is not well understood. In the present study, we examined the morphological changes in the craniofacial structures of mouse embryos\/fetuses at intervals following ethanol treatment and evaluated gene expression patterns in the embryos. <jats:bold>METHODS:<\/jats:bold> Pregnant C57BL\/6J mice were given two doses of ethanol (30 mg\/kg in total) on the morning (7:00 and 11:00 <jats:sc>AM<\/jats:sc>) of day 7. The fetuses were observed at E10.5 and E15.5 grossly and\/or histologically. The expression of <jats:italic>Shh<\/jats:italic> and <jats:italic>Nkx2.1<\/jats:italic> gene transcripts was examined at E8.5 by <jats:italic>in situ<\/jats:italic> hybridization. <jats:bold>RESULTS:<\/jats:bold> Gross and histological abnormalities of the brain and face were found in ethanol\u2010exposed fetuses, and their midline structures were most frequently affected. The midline commissural fibers were often lacking in ethanol\u2010exposed fetuses, even in those cases without external gross malformations. <jats:italic>In situ<\/jats:italic> hybridization revealed down\u2010regulation of <jats:italic>Shh<\/jats:italic> and <jats:italic>Nkx2.1<\/jats:italic> genes in ethanol\u2010exposed embryos. <jats:bold>CONCLUSIONS:<\/jats:bold> The results indicate that ethanol may perturb the expression of some developmental genes at a critical stage of embryonic development and induce holoprosencephaly and other midline craniofacial malformations, including histological brain abnormalities. Birth Defects Research (Part A), 2007. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/bdra.20367","type":"journal-article","created":{"date-parts":[[2007,3,28]],"date-time":"2007-03-28T20:48:46Z","timestamp":1175114926000},"page":"513-523","source":"Crossref","is-referenced-by-count":36,"title":["Sequential developmental changes in holoprosencephalic mouse embryos exposed to ethanol during the gastrulation 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