{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T22:29:10Z","timestamp":1788820150615,"version":"build-2803163510"},"reference-count":65,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["IOS\u20101349668"],"award-info":[{"award-number":["IOS\u20101349668"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DE\u2010023553"],"award-info":[{"award-number":["R01 DE\u2010023553"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R56DE026024\u201002"],"award-info":[{"award-number":["5R56DE026024\u201002"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Congenital heart defects (CHDs) are a leading cause of perinatal mortality, and maternal cigarette smoking is a well\u2010established risk factor. In recent years, electronic cigarette (e\u2010cigarette) use has surged, yet its safety during pregnancy remains poorly defined. Human epidemiologic studies have yielded inconsistent results, underscoring the need for complementary approaches. Developmental vertebrate models provide a cost\u2010effective first\u2010line strategy to identify potential risks. Here, we used the\n                      <jats:italic>Xenopus laevis<\/jats:italic>\n                      model to investigate the effects of e\u2010cigarette aerosol extracts on cardiovascular development during embryogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Xenopus<\/jats:italic>\n                      embryos were exposed during critical stages (20\u201340) to an aerosolized extract of a vanillin flavored e\u2010liquid (e\u2010cigAM\u2010F), nicotine only, or vanillin. Transgenic lines (gata1:GFP for blood, flk1:GFP for vessels) and O\u2010dianisidine staining assessed blood and vascular development. Cardiac structure was evaluated by microscopy and immunofluorescence (troponin T); ventricular area and heart rate were quantified. RT\u2010qPCR and reanalysis of existing RNA\u2010Seq data assessed expression changes in cardiac and hematopoietic genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Embryos exposed to e\u2010cigAM\u2010F had decreased levels of hemoglobin subunits,\n                      <jats:italic>gata1<\/jats:italic>\n                      , and heme biosynthetic genes in craniofacial tissues after exposure. Blood delivery to the head was reduced, though blood remained near the heart. Vascular labeling indicated altered vessel organization but not gross loss of vasculature. Tadpoles exposed to e\u2010cigAM\u2010F had smaller ventricles and modestly reduced heart rate. Early cardiogenic transcripts were also suppressed. Vanillin, but not nicotine, exposure phenocopied the e\u2010cigAM\u2010F effects with respect to heart morphology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Exposure to an aerosolized e\u2010liquid (particularly its vanillin component) perturbs cardiovascular development in\n                      <jats:italic>Xenopus<\/jats:italic>\n                      , manifesting as reduced cranial blood flow, vascular abnormalities, smaller ventricles, and slower heart rate. These results implicate flavoring chemicals (rather than nicotine alone) in developmental cardiotoxicity, underscoring the need for mechanistic and mammalian model studies of inhaled e\u2010liquid constituents.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bdr2.2535","type":"journal-article","created":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T06:00:50Z","timestamp":1758952850000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["E\u2010Cigarette and Vanillin Exposure Disrupts Cardiovascular Development in\n                    <i>Xenopus laevis<\/i>"],"prefix":"10.1002","volume":"117","author":[{"suffix":"III","given":"James E.","family":"Black","sequence":"first","affiliation":[{"name":"Department of Biology Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas O.","family":"Raymond","sequence":"additional","affiliation":[{"name":"Department of Biology Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1427-9140","authenticated-orcid":false,"given":"Amanda J. G.","family":"Dickinson","sequence":"additional","affiliation":[{"name":"Department of Biology Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00283.2020"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V77.6.1334.1334"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci13101417"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jog.14294"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1227145"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/01480549009032286"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2016.03.001"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389557519666190312164355"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquatox.2021.105995"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1561"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1089\/jmf.2012.0162"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12012\u2010024\u201009850\u20109"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0960327120947785"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201028723\u20100"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2018.07.001"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00304.2018"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/ntr\/ntac111"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.23.10713"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2021.09.004"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0115305"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1139\/bcb\u20102017\u20100122"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.2550090603"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1520-6866(2000)20:2<87::AID-TCM4>3.0.CO;2-6"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsbl.2020.0361"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17328"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1571"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcdd3020021"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2019.110945"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408444.2025.2497754"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25010194"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20107883\u20100_15"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci46322"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3791\/52062"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.22864"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0185729"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12884\u2010020\u201003247\u20106"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1177\/10556656231163400"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00246\u2010012\u20100470\u2010x"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ypmed.2022.107375"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2005.01.015"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2023.116631"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1113\/jp286493"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.121.317749"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u201060761\u2010849\u20102_15"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.23300"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.8b00084"},{"key":"e_1_2_10_48_1","volume-title":"Normal Table of Xenopus laevis\u00a0(Daudin): A Systematical and Chronological Survey of the Development From the Fertilized Egg Till the End of Metamorphosis","author":"Nieuwkoop P. 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