{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:55:49Z","timestamp":1790078149261,"version":"4.0.1"},"reference-count":31,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2014,7,26]],"date-time":"2014-07-26T00:00:00Z","timestamp":1406332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD072251"],"award-info":[{"award-number":["HD072251"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:p>Background: Valproic acid (VPA) is a commonly prescribed drug for those affected by epilepsy and bipolar disorders. VPA has a well known teratogenic potential, causing a variety of birth defects including neural tube defects (NTDs) and other congenital malformations, when women are treated with this medication during pregnancy. Unfortunately, the mechanism by which VPA is teratogenic remains unknown, although a range of potential mechanisms including histone deacetylase inhibition and folate antagonism have been proposed. The latter is of considerable importance, as clinicians need to know if additional folate supplements can prevent VPA\u2010induced defects. <jats:bold>Methods:<\/jats:bold> We herein approach this question experimentally, using enzyme\u2010linked immunosorbent assay assays and cell culture modeling, to demonstrate that VPA serves as a noncompetitive inhibitor of the high affinity folate receptors. <jats:bold>Results:<\/jats:bold> Binding affinities experimentally determined through enzyme\u2010linked immunosorbent assay assays indicate that VPA serves as a noncompetitive substrate that can lessen the ability of the three primary folate forms to bind to the high affinity folate receptors. Tests in HEK293T cells indicate that the membrane\u2010bound folate receptors of VPA treated cells bind significantly lower amounts of folic acid than do untreated cells. <jats:bold>Conclusion:<\/jats:bold> If these data translate to the overall transport and subsequent bioavailability of folates, noncompetitive inhibition of the folate receptors by VPA may serve to lower the bioavailable folates in VPA treated mothers. This represents a novel mechanism by which in utero VPA exposure could be disrupting developmental processes by noncompetitively binding to the folate receptors during embryogenesis, thus inducing the wide range of defects seen in babies born to VPA treated mothers. Birth Defects Research (Part A) 100:592\u2013597, 2014. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/bdra.23277","type":"journal-article","created":{"date-parts":[[2014,7,26]],"date-time":"2014-07-26T06:21:36Z","timestamp":1406355696000},"page":"592-597","source":"Crossref","is-referenced-by-count":66,"title":["Brief report novel mechanism for valproate\u2010induced teratogenicity"],"prefix":"10.1002","volume":"100","author":[{"given":"Kristin","family":"Fathe","sequence":"first","affiliation":[{"name":"Department of Molecular Biosciences University of Texas Austin Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Palacios","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences Dell Pediatric Research Institute, University of Texas Austin Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard H.","family":"Finnell","sequence":"additional","affiliation":[{"name":"Department of 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