{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T15:59:06Z","timestamp":1780502346734,"version":"3.54.1"},"reference-count":41,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100003321","name":"Queen's University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP 115188"],"award-info":[{"award-number":["MOP 115188"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Placenta"],"published-print":{"date-parts":[[2021,9]]},"DOI":"10.1016\/j.placenta.2021.07.299","type":"journal-article","created":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T02:05:09Z","timestamp":1627610709000},"page":"141-152","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"special_numbering":"C","title":["Characterizing the effects of in utero valproic acid exposure on murine fetoplacental development"],"prefix":"10.1016","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9200-3652","authenticated-orcid":false,"given":"Sidra","family":"Shafique","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1088-5538","authenticated-orcid":false,"given":"Louise M.","family":"Winn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.placenta.2021.07.299_bib1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1093\/inthealth\/ihy006","article-title":"Developmental origins of health and disease: the relevance to developing nations","volume":"10","author":"Mandy","year":"2018","journal-title":"Int. Health"},{"key":"10.1016\/j.placenta.2021.07.299_bib2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fendo.2018.00570","article-title":"Regulation of placental development and its impact on fetal growth\u2014new insights from mouse models","volume":"9","author":"Woods","year":"2018","journal-title":"Front. Endocrinol."},{"key":"10.1016\/j.placenta.2021.07.299_bib3","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/35080570","article-title":"Placental development: lessons from mouse mutants","volume":"2","author":"Rossant","year":"2001","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.placenta.2021.07.299_bib4","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s00281-016-0574-0","article-title":"The decidua-the maternal bed embracing the embryo-maintains the pregnancy","author":"Mori","year":"2016","journal-title":"Semin. Immunopathol."},{"key":"10.1016\/j.placenta.2021.07.299_bib5","doi-asserted-by":"crossref","first-page":"100","DOI":"10.4103\/2096-2924.216864","article-title":"Developmental aspect of decidual patterning","volume":"1","author":"Zhou","year":"2017","journal-title":"Reprod. Dev. Med."},{"key":"10.1016\/j.placenta.2021.07.299_bib6","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1007\/s11515-011-1120-z","article-title":"Developmental genes during placentation: insights from mouse mutants","volume":"6","author":"Lu","year":"2011","journal-title":"Front. Biol. China"},{"key":"10.1016\/j.placenta.2021.07.299_bib7","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1159\/000144801","article-title":"Development of trophoblast and placenta of the mouse: a reinvestigation with regard to the in vitro culture of mouse trophoblast and placenta","volume":"98","author":"M\u00fcntener","year":"1977","journal-title":"Cells Tissues Organs"},{"key":"10.1016\/j.placenta.2021.07.299_bib8","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3389\/fphys.2016.00028","article-title":"Placental adaptation: what can we learn from Birthweight:placental weight ratio?","volume":"7","author":"Hayward","year":"2016","journal-title":"Front. Physiol."},{"key":"10.1016\/j.placenta.2021.07.299_bib9","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/978-3-642-00663-0_6","article-title":"Receptor- and reactive intermediate-mediated mechanisms of teratogenesis","volume":"196","author":"Wells","year":"2010","journal-title":"Handb. Exp. Pharmacol."},{"key":"10.1016\/j.placenta.2021.07.299_bib10","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/tera.1420350319","article-title":"Teratogen update: valproic acid","volume":"35","author":"Lammer","year":"1987","journal-title":"Teratology"},{"issue":"Suppl 6","key":"10.1016\/j.placenta.2021.07.299_bib11","first-page":"9","article-title":"Treatment of bipolar disorder","volume":"64","author":"M\u00f6ller","year":"2003","journal-title":"J. Clin. Psychiatr."},{"key":"10.1016\/j.placenta.2021.07.299_bib12","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1093\/toxsci\/kfq140","article-title":"Genetic and maternal effects on valproic acid teratogenesis in C57BL\/6J and DBA\/2J mice","volume":"116","author":"Downing","year":"2010","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.placenta.2021.07.299_bib13","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1056\/NEJMoa0907328","article-title":"Valproic acid monotherapy in pregnancy and major congenital malformations","volume":"362","author":"Jentink","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.placenta.2021.07.299_bib14","first-page":"441","article-title":"Major malformations with valproic acid","volume":"52","author":"Koren","year":"2006","journal-title":"Can. Fam. Physician"},{"key":"10.1016\/j.placenta.2021.07.299_bib15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.reprotox.2009.02.014","article-title":"Valproic acid in pregnancy: how much are we endangering the embryo and fetus?","volume":"28","author":"Ornoy","year":"2009","journal-title":"Reprod. Toxicol."},{"key":"10.1016\/j.placenta.2021.07.299_bib16","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/S0022-3476(80)80517-8","article-title":"Teratogenicity of valproic acid","volume":"97","author":"Dalens","year":"1980","journal-title":"J. Pediatr."},{"key":"10.1016\/j.placenta.2021.07.299_bib17","first-page":"933","article-title":"Valproic acid therapy and neural tube defects","volume":"132","author":"Garden","year":"1985","journal-title":"Can. Med. Assoc. J."},{"key":"10.1016\/j.placenta.2021.07.299_bib18","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.pharmthera.2018.05.007","article-title":"Autism spectrum disorder: classification, diagnosis and therapy","volume":"190","author":"Sharma","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.placenta.2021.07.299_bib19","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1212\/WNL.0000000000001182","article-title":"IQ at 6 years after in utero exposure to antiepileptic drugs: a controlled cohort study","volume":"84","author":"Baker","year":"2015","journal-title":"Neurology"},{"key":"10.1016\/j.placenta.2021.07.299_bib20","first-page":"153","article-title":"Valproic acid transfer across human placental cotyledon during dual perfusion in vitro","volume":"17","author":"Semczuk-Sikora","year":"2010","journal-title":"Ann. Agric. Environ. Med."},{"key":"10.1016\/j.placenta.2021.07.299_bib21","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1111\/epi.14721","article-title":"The effects of valproic acid on early pregnancy human placentas: pilot ex vivo analysis in cultured placental villi","volume":"60","author":"Tetro","year":"2019","journal-title":"Epilepsia"},{"key":"10.1016\/j.placenta.2021.07.299_bib22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1477-7827-6-34","article-title":"In vivo quantification of embryonic and placental growth during gestation in mice using micro-ultrasound","volume":"6","author":"Mu","year":"2008","journal-title":"Reprod. Biol. Endocrinol."},{"key":"10.1016\/j.placenta.2021.07.299_bib23","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.taap.2005.07.008","article-title":"Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice","volume":"211","author":"Dawson","year":"2006","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.placenta.2021.07.299_bib24","first-page":"92","article-title":"Morphometric study of the teratogenic effect of artesunate on the central nervous system of the wistar rat foetus","volume":"19","author":"Mesembe","year":"2005","journal-title":"Niger. J. Physiol. Sci."},{"key":"10.1016\/j.placenta.2021.07.299_bib25","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S1567-5769(01)00183-7","article-title":"Maternal immune stimulation in mice decreases fetal malformations caused by teratogens","volume":"2","author":"Holladay","year":"2002","journal-title":"Int. Immunopharm."},{"key":"10.1016\/j.placenta.2021.07.299_bib26","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3126\/nmcj.v21i3.26459","article-title":"The effect of piracetam on valproic acid induced congenital malformations in Swiss albino mice","volume":"21","author":"Shrestha","year":"2019","journal-title":"Nepal Med. Coll. J."},{"key":"10.1016\/j.placenta.2021.07.299_bib27","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1136\/jnnp-2012-304270","article-title":"Liverpool and Manchester Neurodevelopment Group, the prevalence of neurodevelopmental disorders in children prenatally exposed to antiepileptic drugs","volume":"84","author":"Bromley","year":"2013","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"10.1016\/j.placenta.2021.07.299_bib28","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.neuroscience.2013.03.030","article-title":"Rearrangement of the dendritic morphology in limbic regions and altered exploratory behavior in a rat model of autism spectrum disorder","volume":"241","author":"Bringas","year":"2013","journal-title":"Neuroscience"},{"key":"10.1016\/j.placenta.2021.07.299_bib29","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/0041-008X(85)90081-X","article-title":"Teratogenic valproic acid concentrations: infusion by implanted minipumps vs conventional injection regimen in the mouse","volume":"80","author":"Nau","year":"1985","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.placenta.2021.07.299_bib30","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1002\/bdra.23277","article-title":"Novel mechanism for valproate-induced teratogenicity","volume":"100","author":"Fathe","year":"2014","journal-title":"Birth Defects Res. Part A Clin. Mol. Teratol."},{"key":"10.1016\/j.placenta.2021.07.299_bib31","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1124\/mol.111.072314","article-title":"Valproic acid increases formation of reactive oxygen species and induces apoptosis in postimplantation embryos: a role for oxidative stress in valproic acid-induced neural tube defects","volume":"80","author":"Tung","year":"2011","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.placenta.2021.07.299_bib32","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1002\/bdrb.21018","article-title":"Reduction in valproic acid-induced neural tube defects by maternal immune stimulation: role of apoptosis","volume":"95","author":"Mallela","year":"2012","journal-title":"Birth Defects Res. Part B Dev. Reproductive Toxicol."},{"key":"10.1016\/j.placenta.2021.07.299_bib33","first-page":"3063","article-title":"Congenital eye defects due to failure of embryonic eyelid closure | IOVS | ARVO Journals","volume":"54","author":"Meng","year":"2013","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.placenta.2021.07.299_bib34","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/j.neuroscience.2009.07.021","article-title":"Prenatal exposure to valproic acid leads to reduced expression of synaptic adhesion molecule neuroligin 3 in mice","volume":"163","author":"Kolozsi","year":"2009","journal-title":"Neuroscience"},{"key":"10.1016\/j.placenta.2021.07.299_bib35","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0892-0362(99)00083-5","article-title":"Prenatal exposure of rats to valproic acid reproduces the cerebellar anomalies associated with autism","volume":"22","author":"Ingram","year":"2000","journal-title":"Neurotoxicol. Teratol."},{"key":"10.1016\/j.placenta.2021.07.299_bib36","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/S1474-4422(05)70224-6","article-title":"Birth defects after prenatal exposure to antiepileptic drugs","volume":"4","author":"Perucca","year":"2005","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.placenta.2021.07.299_bib37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphys.2018.01884","article-title":"The possible role of placental morphometry in the detection of fetal growth restriction","volume":"9","author":"Salavati","year":"2019","journal-title":"Front. Physiol."},{"key":"10.1016\/j.placenta.2021.07.299_bib38","first-page":"275","article-title":"Phenotypic analysis of the mouse placenta","volume":"121","author":"Natale","year":"2006","journal-title":"Methods Mol. Med."},{"key":"10.1016\/j.placenta.2021.07.299_bib39","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1095\/biolreprod.103.024166","article-title":"Developmental dynamics of the definitive mouse placenta assessed by Stereology1","volume":"70","author":"Coan","year":"2004","journal-title":"Biol. Reprod."},{"key":"10.1016\/j.placenta.2021.07.299_bib40","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/tera.1420450605","article-title":"Valproic acid\u2010induced placental and teratogenic effects in rats","volume":"45","author":"Khera","year":"1992","journal-title":"Teratology"},{"key":"10.1016\/j.placenta.2021.07.299_bib41","first-page":"1","article-title":"Associations between the features of gross placental morphology and birthweight","author":"Freedman","year":"2018","journal-title":"Pediatr. Dev. Pathol."}],"container-title":["Placenta"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S014340042100494X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S014340042100494X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T23:56:47Z","timestamp":1778716607000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S014340042100494X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9]]},"references-count":41,"alternative-id":["S014340042100494X"],"URL":"https:\/\/doi.org\/10.1016\/j.placenta.2021.07.299","relation":{},"ISSN":["0143-4004"],"issn-type":[{"value":"0143-4004","type":"print"}],"subject":[],"published":{"date-parts":[[2021,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Characterizing the effects of in utero valproic acid exposure on murine fetoplacental development","name":"articletitle","label":"Article Title"},{"value":"Placenta","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.placenta.2021.07.299","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}