{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T23:51:39Z","timestamp":1770681099127,"version":"3.49.0"},"reference-count":32,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T00:00:00Z","timestamp":1572307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2019,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Recently, the use of the antiepileptic drug valproic acid (VPA) for the treatment of psychiatric conditions has been on the rise. However, studies have shown that in utero VPA exposure can affect embryonic development, including being associated with congenital heart defects. One proposed mechanism of VPA\u2010initiated teratogenicity is the inhibition of histone deacetylase, which is involved in the regulation of transcription factors that regulate cardiogenesis. Myocyte enhancing factor 2C (<jats:italic>Mef2c<\/jats:italic>), a transcription factor involved in the development of cardiac structure and cardiomyocyte differentiation, has been shown to increase in response to in utero VPA exposure, associating with contractile dysfunction and myocardial disorganization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To characterize the effects of VPA on murine heart development, pregnant CD\u20101 mice were dosed with 400\u2009mg\/kg of VPA on gestational day (GD) 9. Using high\u2010resolution ultrasound, we examined the effects of VPA on cardiac contractile function on GD 14\u201318, with fetal hearts being harvested on GD 19 for histological analysis. Lastly, we conducted quantitative real\u2010time polymerase chain reaction to measure the relative <jats:italic>Mef2c<\/jats:italic> gene expression in GD 16 murine hearts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed structural anomalies at GD 19 in the hearts of VPA\u2010treated mice. Additionally, our results showed alterations in measures of cardiac contractility, with a decrease or increase in cardiac contractile ability in VPA\u2010treated mice depending on the GD and measurement taken.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results further characterize the effects of VPA on heart development and suggest that alterations in <jats:italic>Mef2c<\/jats:italic> gene expression, at least on GD 16, do not mediate VPA\u2010induced cardiotoxicity in CD\u20101 mice.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.1610","type":"journal-article","created":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T12:35:26Z","timestamp":1572352526000},"page":"1551-1560","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Characterizing the effects of in utero exposure to valproic acid on murine fetal heart development"],"prefix":"10.1002","volume":"111","author":[{"given":"Nicola A.","family":"Philbrook","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Nikolovska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca D.","family":"Maciver","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine L.","family":"Belanger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1088-5538","authenticated-orcid":false,"given":"Louise M.","family":"Winn","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences Queen's University  Kingston Ontario Canada"},{"name":"School of Environmental Studies Queen's University  Kingston Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,10,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfv169"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23147"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2014.04.001"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.32.9.724"},{"key":"e_1_2_6_6_1","unstructured":"Congenital Heart Defects | National Heart Lung and Blood Institute. (2019). Retrieved from.https:\/\/www.nhlbi.nih.gov\/health-topics\/congenital-heart-defects"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2005.07.008"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/embo-reports\/kvf053"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-3425fje"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028725"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(97)00215-0"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0907328"},{"key":"e_1_2_6_13_1","first-page":"e50994","article-title":"In utero measurement of heart rate in mouse by noninvasive m\u2010mode echocardiography","volume":"81","author":"Kim W.","year":"2013","journal-title":"JoVE (Journal of Visualized Experiments)"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(20010115)98:2<168::AID-AJMG1026>3.0.CO;2-O"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2014.128"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5317.1404"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-9182-2_26"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002119"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1520-6866(1996)16:2<97::AID-TCM4>3.0.CO;2-A"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.10030"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carpath.2007.06.005"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2009.02.014"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101287200"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.008367"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2013.01.004"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420480206"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30107-8"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13021"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2010.08.001"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35438"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/1423-0127-17-16"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M510217200"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.19.8456-8464.2005"}],"container-title":["Birth Defects Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdr2.1610","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdr2.1610","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bdr2.1610","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdr2.1610","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T12:57:21Z","timestamp":1694177841000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdr2.1610"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,29]]},"references-count":32,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2019,11,15]]}},"alternative-id":["10.1002\/bdr2.1610"],"URL":"https:\/\/doi.org\/10.1002\/bdr2.1610","archive":["Portico"],"relation":{},"ISSN":["2472-1727","2472-1727"],"issn-type":[{"value":"2472-1727","type":"print"},{"value":"2472-1727","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,29]]},"assertion":[{"value":"2019-06-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}