{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T01:21:02Z","timestamp":1793064062317,"version":"4.5.0"},"reference-count":54,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,2,10]],"date-time":"2012-02-10T00:00:00Z","timestamp":1328832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Fetal alcohol spectrum disorders (<jats:styled-content style=\"fixed-case\">FASD<\/jats:styled-content>) are a leading cause of neurodevelopmental disability. The mechanisms underlying <jats:styled-content style=\"fixed-case\">FASD<\/jats:styled-content> are incompletely understood, and biomarkers to identify those at risk are lacking. Here, we perform metabolomic analysis of embryoid bodies and neural lineages derived from human embryonic stem (<jats:styled-content style=\"fixed-case\">hES<\/jats:styled-content>) cells to identify the neural secretome produced in response to ethanol (<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>t<jats:styled-content style=\"fixed-case\">OH<\/jats:styled-content>) exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">WA<\/jats:styled-content>01 and <jats:styled-content style=\"fixed-case\">WA<\/jats:styled-content>09 <jats:styled-content style=\"fixed-case\">hES<\/jats:styled-content> cells were differentiated into embryoid bodies, neural progenitors, or neurons. Cells along this progression were cultured for 4\u00a0days with 0, 0.1, or 0.3% <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>t<jats:styled-content style=\"fixed-case\">OH<\/jats:styled-content>. Supernatants were subjected to <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>18 chromatography followed by <jats:styled-content style=\"fixed-case\">ESI<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">QTOF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>. Features were annotated using public databases, and the identities of 4 putative biomarkers were confirmed with purified standards and comparative <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>EtOH treatment induced statistically significant changes to metabolite abundance in human embryoid bodies (180 features), neural progenitors (76 features), and neurons (42 features). There were no shared significant features between different cell types. Fifteen features showed a dose\u2013response to <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>t<jats:styled-content style=\"fixed-case\">OH<\/jats:styled-content>. Four chemical identities were confirmed: <jats:sc>l<\/jats:sc>\u2010thyroxine, 5\u2032\u2010methylthioadenosine, and the tryptophan metabolites, <jats:sc>l<\/jats:sc>\u2010kynurenine and indoleacetaldehyde. One feature with a putative annotation of succinyladenosine was significantly increased in both <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>t<jats:styled-content style=\"fixed-case\">OH<\/jats:styled-content> treatments. Additional features were selective to <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>t<jats:styled-content style=\"fixed-case\">OH<\/jats:styled-content> treatment but were not annotated in public databases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>EtOH exposure induces statistically significant changes to the metabolome profile of human embryoid bodies, neural progenitors, and neurons. Several of these metabolites are normally present in human serum, suggesting their usefulness as potential serum <jats:styled-content style=\"fixed-case\">FASD<\/jats:styled-content> biomarkers. These findings suggest the biochemical pathways that are affected by <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>t<jats:styled-content style=\"fixed-case\">OH<\/jats:styled-content> in the developing nervous system and delineate mechanisms of alcohol injury during human development.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1530-0277.2011.01732.x","type":"journal-article","created":{"date-parts":[[2012,2,11]],"date-time":"2012-02-11T02:05:44Z","timestamp":1328925944000},"page":"1314-1324","source":"Crossref","is-referenced-by-count":26,"title":["Metabolic Biomarkers of Prenatal Alcohol Exposure in Human Embryonic Stem Cell\u2013Derived Neural Lineages"],"prefix":"10.1111","volume":"36","author":[{"given":"Jessica A.","family":"Palmer","sequence":"first","affiliation":[{"name":"Department of Animal Sciences University of Wisconsin\u2010Madison Madison Wisconsin"},{"name":"Stemina Biomarker Discovery Inc. Madison Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley M.","family":"Poenitzsch","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences University of Wisconsin\u2010Madison Madison Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences University of Wisconsin\u2010Madison Madison Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin R.","family":"Conard","sequence":"additional","affiliation":[{"name":"Stemina Biomarker Discovery Inc. Madison Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"West","sequence":"additional","affiliation":[{"name":"Stemina Biomarker Discovery Inc. Madison Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela G.","family":"Cezar","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences University of Wisconsin\u2010Madison Madison Wisconsin"},{"name":"Stemina Biomarker Discovery Inc. Madison Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,2,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2003.11.016"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agp005"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2004-0094"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1330390"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1993.tb03688.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1991.tb00544.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2007.0022"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-200306000-00004"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.20182"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2002.tb02431.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(87)91490-2"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1991.tb00578.x"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(87)90199-2"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.173.3992.149"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1013713905833"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(74)90988-7"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6768132"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-1014"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/1029842021000010884"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1990.tb00503.x"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(79)90785-6"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(99)00024-9"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2009.0529"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(77)90213-X"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1990.tb00500.x"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac031386"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2010.01170.x"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(96)00282-1"},{"key":"e_1_2_6_30_1","first-page":"23","volume-title":"The Physiology of Polyamines","author":"Mendez JD","year":"1989"},{"key":"e_1_2_6_31_1","unstructured":"MW Miller 2006 Oxford University Press New York"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(87)90726-8"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10491"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(71)91040-3"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2007.00354.x"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/74447"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2010.01.004"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0892-0362(98)00049-X"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1997.tb03767.x"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0940-2993(11)80077-1"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1995.tb01494.x"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2010.01373.x"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac051437y"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00125a012"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-504"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(77)90109-5"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2009.07.002"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20713"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5391.1145"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2007.11.003"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpc.2007.03.006"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2010.05.007"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2010.12.019"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2006.00008.x"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1201-1129"}],"container-title":["Alcoholism: Clinical and Experimental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1530-0277.2011.01732.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1530-0277.2011.01732.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T12:27:04Z","timestamp":1698755224000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1530-0277.2011.01732.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2,10]]},"references-count":54,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2012,8]]}},"alternative-id":["10.1111\/j.1530-0277.2011.01732.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1530-0277.2011.01732.x","archive":["Portico"],"relation":{},"ISSN":["0145-6008","1530-0277"],"issn-type":[{"value":"0145-6008","type":"print"},{"value":"1530-0277","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,2,10]]}}}