{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T16:13:59Z","timestamp":1765728839114,"version":"3.40.5"},"reference-count":66,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T00:00:00Z","timestamp":1655856000000},"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":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Excessive alcohol consumption during pregnancy is associated with high risk of congenital heart defects, but it is unclear how alcohol specifically affects heart development during the acute aftermath of a maternal binge drinking episode. We hypothesize that administration of a single maternal binge dose of alcohol to pregnant mice at embryonic day 9.5 (E9.5) causes perturbations in the expression patterns of specific genes in the developing heart in the acute period (1\u20133\u2009days) following the binge episode. To test this hypothesis and identify strong candidate ethanol\u2010sensitive target genes of interest, we adapted a mouse binge alcohol model that is associated with a high incidence of congenital heart defects as described below.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods\/Results<\/jats:title><jats:p>Pregnant mice were administered a single dose of alcohol (2.5\u00a0g\/kg in saline) or control (saline alone) via oral gavage. To evaluate the impact of maternal binge alcohol on cardiac gene expression profiles, we isolated embryonic hearts from both groups (<jats:italic>n<\/jats:italic>\u00a0=\u00a05\/group) at 24, 48, and 72\u2009h post\u2010gavage for transcriptomic analyses. RNA was extracted and evaluated using quantitative RNA\u2010sequencing (RNA\u2010Seq) methods. To identify a cohort of binge\u2010altered cardiac genes, we set the threshold for change at &gt;2.0\u2010fold difference with adjusted<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 versus control.\u00a0 RNA\u2010Seq analysis of cardiac gene expression revealed that of the 17 genes that were altered within the first 48\u2009h post\u2010binge, with the largest category consisting of transcription factors (<jats:italic>Alx1, Alx4, HoxB7, HoxD8,<\/jats:italic>and<jats:italic>Runx2<\/jats:italic>), followed by signaling molecules (<jats:italic>Adamts18, Dkk2, Rtl1,<\/jats:italic>and<jats:italic>Wnt7a<\/jats:italic>). Furthermore, multiple comparative and pathway analyses suggested that several of the candidate genes identified through differential RNA\u2010Seq analysis may interact through certain common pathways. To investigate this further, we performed gene\u2010specific qPCR analyses for three representative candidate targets:<jats:italic>Runx2<\/jats:italic>,<jats:italic>Wnt7a<\/jats:italic>, and<jats:italic>Mlxipl<\/jats:italic>. Notably, only<jats:italic>Wnt7a<\/jats:italic>showed significantly (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) decreased expression in response to maternal binge alcohol in the qPCR assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings identify<jats:italic>Wnt7a<\/jats:italic>and a short list of potential other candidate genes and pathways for further study, which could provide mechanistic insights into how maternal binge alcohol consumption produces congenital cardiac malformations.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14880","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T04:20:52Z","timestamp":1655094052000},"page":"1433-1448","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Maternal binge alcohol consumption leads to distinctive acute perturbations in embryonic cardiac gene expression profiles"],"prefix":"10.1111","volume":"46","author":[{"given":"Shani","family":"Abraham","sequence":"first","affiliation":[{"name":"Division of Metabolic and Cardiovascular Science, Burnett School of Biomedical Sciences, College of Medicine University of Central Florida Orlando Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chad","family":"Lindo","sequence":"additional","affiliation":[{"name":"Division of Metabolic and Cardiovascular Science, Burnett School of Biomedical Sciences, College of Medicine University of Central Florida Orlando Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Peoples","sequence":"additional","affiliation":[{"name":"Division of Metabolic and Cardiovascular Science, Burnett School of Biomedical Sciences, College of Medicine University of Central Florida Orlando Florida 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