{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T17:33:53Z","timestamp":1760204033368},"reference-count":66,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2004,11,2]],"date-time":"2004-11-02T00:00:00Z","timestamp":1099353600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2004,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Valproic acid (VPA) is widely used to treat epilepsy and bipolar disorder and is also a potent teratogen, but its teratogenic mechanisms are unknown. We have attempted to describe a fundamental role of the Polycomb group (Pc\u2010G) in VPA\u2010induced transformations of the axial skeleton.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Pregnant NMRI mice were given a single subcutaneous injection of vehicle or VPA (800 mg\/kg) on gestation day (GD) 8. The expression of genes encoding Polycomb and trithorax groups was measured by quantitative real\u2010time RT\u2010PCR using total RNA isolated from the embryos exposed to vehicle or VPA for 1, 3, and 6 hr. In addition, the use of two less teratogenic antiepileptic chemicals valpromide (VPD) and valnoctamide (VCD) provide reliable evidence to support the relationship between VPA teratogenicity and the Polycomb group.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>At a teratogenic level, VPA inhibits the expression of the Polycomb group genes, including <jats:italic>Eed<\/jats:italic>, <jats:italic>Ezh2<\/jats:italic>, <jats:italic>Zfp144<\/jats:italic>, <jats:italic>Bmi1<\/jats:italic>, <jats:italic>Cbx2<\/jats:italic>, <jats:italic>Rnf2<\/jats:italic>, and <jats:italic>YY1<\/jats:italic> in the mouse embryos. In contrast, neither VPD nor VCD have significant effects on the expression of those genes affected by VPA. The trithorax group (trx\u2010G) gene <jats:italic>MLL<\/jats:italic>, which is known to be required to maintain homeobox gene expression such as the Polycomb gene, is not affected by a teratogenic dose of VPA.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>We propose that, during embryonic development, VPA may affect the gene silencing pathway mediated by the Polycomb group complex. The epigenetic mechanism of VPA teratogenicity on anteroposterior patterning is suspected. Birth Defects Research (Part A), 2004. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.20085","type":"journal-article","created":{"date-parts":[[2004,11,11]],"date-time":"2004-11-11T08:45:55Z","timestamp":1100162755000},"page":"870-879","source":"Crossref","is-referenced-by-count":14,"title":["Polycomb homologs are involved in teratogenicity of valproic acid in 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