{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T08:54:01Z","timestamp":1767862441328,"version":"3.49.0"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T00:00:00Z","timestamp":1523923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["506\/13"],"award-info":[{"award-number":["506\/13"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>In utero exposure to valproic acid (<jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>) has been associated with worse pregnancy outcomes compared to all other antiepileptic drugs. We have previously shown that <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content> alters the expression of placental transporters for hormones and nutrients in\u00a0vitro and in pregnant mice. Here, our aim was to characterize the effects of short exposure to <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content> on the expression of carriers for compounds essential for fetal development in human placentas ex\u00a0vivo, under controlled conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Placentas were obtained from cesarean deliveries of women with no known epilepsy. Cotyledons were cannulated and perfused in the absence or the presence of <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content> (42, 83, or 166\u00a0\u03bcg\/mL; n\u00a0=\u00a06\/group) in the maternal perfusate over 180\u00a0minutes. A customized gene panel array was used to analyze the expression of carrier genes in the perfused cotyledons. We additionally measured in the perfused placentas folic acid concentrations and histone acetylation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content> significantly altered the <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels of major carriers for folic acid, glucose, choline, thyroid hormones, and serotonin (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05) and reduced placental folate concentrations by 25%\u201035% (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.059). The effects were observed at therapeutic concentrations sufficient to enhance placental histone acetylation, and some were concentration\u2010dependent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Our results point to the placenta as a novel target of <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>, implying potential involvement of the placenta in <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>'s adverse fetal outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.14078","type":"journal-article","created":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T06:01:31Z","timestamp":1524031291000},"page":"993-1003","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Adverse placental effects of valproic acid: Studies in perfused human placentas"],"prefix":"10.1111","volume":"59","author":[{"given":"Miriam","family":"Rubinchik\u2010Stern","sequence":"first","affiliation":[{"name":"Institute for Drug Research School of Pharmacy The Hebrew University of Jerusalem Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam","family":"Shmuel","sequence":"additional","affiliation":[{"name":"Institute for Drug Research School of Pharmacy The Hebrew University of Jerusalem Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Bar","sequence":"additional","affiliation":[{"name":"Department of Obstetrics &amp; Gynecology Edith Wolfson Medical Center Holon Israel"},{"name":"Sackler School of Medicine Tel Aviv University Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"Kovo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics &amp; Gynecology Edith Wolfson Medical Center Holon Israel"},{"name":"Sackler School of Medicine Tel Aviv University Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Eyal","sequence":"additional","affiliation":[{"name":"Institute for Drug Research School of Pharmacy The Hebrew University of Jerusalem Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,4,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13021"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25031"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13872"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2018.02.004"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.2270"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0803531"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70323-X"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001182"},{"key":"e_1_2_9_10_1","unstructured":"European Medicines Agency.Assessment report. 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