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The teratogenic effects of alcohol have long been publicized; yet fetal alcohol exposure is one of the most common preventable causes of birth defects. Currently, alcohol abstinence during pregnancy is the best and only way to prevent FASD. However, alcohol consumption remains astoundingly prevalent among pregnant women; therefore, additional measures need to be made available to help protect the developing embryo before irreparable damage is done. Maternal nutritional interventions using methyl donors have been investigated as potential preventative measures to mitigate the adverse effects of fetal alcohol exposure. Here, we show that a single acute preimplantation (E2.5; 8\u2010cell stage) fetal alcohol exposure (2\u2009\u00d7\u20092.5\u2009g\/kg ethanol with a 2h interval) in mice leads to long\u2010term FASD\u2010like morphological phenotypes (e.g. growth restriction, brain malformations, skeletal delays) in late\u2010gestation embryos (E18.5) and demonstrate that supplementing the maternal diet with a combination of four methyl donor nutrients, folic acid, choline, betaine, and vitamin B12, prior to conception and throughout gestation effectively reduces the incidence and severity of alcohol\u2010induced morphological defects without altering DNA methylation status of imprinting control regions and regulation of associated imprinted genes. This study clearly supports that preimplantation embryos are vulnerable to the teratogenic effects of alcohol, emphasizes the dangers of maternal alcohol consumption during early gestation, and provides a potential proactive maternal nutritional intervention to minimize FASD progression, reinforcing the importance of adequate preconception and prenatal nutrition.<\/jats:p>","DOI":"10.1096\/fj.202201564r","type":"journal-article","created":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T10:45:35Z","timestamp":1677667535000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Mitigating the detrimental developmental impact of early fetal alcohol exposure using a maternal methyl donor\u2010enriched diet"],"prefix":"10.1096","volume":"37","author":[{"given":"M\u00e9lanie","family":"Breton\u2010Larriv\u00e9e","sequence":"first","affiliation":[{"name":"Centre Hospitalier Universitaire Sainte\u2010Justine Research Center  Montreal Canada"},{"name":"Department of Biochemistry and Molecular Medicine Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Elder","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire Sainte\u2010Justine Research Center  Montreal Canada"},{"name":"Department of Biochemistry and Molecular Medicine Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa\u2010Marie","family":"Legault","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire Sainte\u2010Justine Research Center  Montreal Canada"},{"name":"Department of Biochemistry and Molecular Medicine Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Langford\u2010Avelar","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire Sainte\u2010Justine Research Center  Montreal Canada"},{"name":"Department of Biochemistry and Molecular Medicine Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda J.","family":"MacFarlane","sequence":"additional","affiliation":[{"name":"Agriculture, Food, and Nutrition Evidence Center Texas A&amp;M University  Texas Fort Worth USA"},{"name":"Department of Nutrition Texas A&amp;M University  College Station Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3504-8253","authenticated-orcid":false,"given":"Serge","family":"McGraw","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire Sainte\u2010Justine Research Center  Montreal Canada"},{"name":"Department of Biochemistry and Molecular Medicine Universit\u00e9 de Montr\u00e9al  Montreal Canada"},{"name":"Department of Obstetrics and Gynecology Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(73)91092-1"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2015-4256"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2013.07.013"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30150-4"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13103452"},{"key":"e_1_2_11_7_1","volume-title":"Australian guidelines to reduce health risks from drinking alcohol","author":"Lewis P","year":"2009"},{"key":"e_1_2_11_8_1","volume-title":"Advisory on alcohol use during pregnancy. 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