{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:59:22Z","timestamp":1790218762027,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T00:00:00Z","timestamp":1639353600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/G007993\/1"],"award-info":[{"award-number":["BB\/G007993\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:sec><jats:title>Scope<\/jats:title><jats:p>Persistent DNA methylation changes may mediate effects of early\u2010life exposures on later\u2010life health. Human lifespan is challenging for prospective studies, therefore data from longitudinal studies are limited. Projecting data from mouse models of early\u2010life exposure to human studies offers a tool to address this challenge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>C57BL\/6J mice were fed low\/normal folate diets before and during pregnancy and lactation. Genome\u2010wide promoter methylation was measured in male offspring livers at 17.5 days gestation and 28 weeks. Eight promoters were concurrently hypermethylated by folate depletion in fetuses and adults (&gt;1.10 fold\u2010change; <jats:italic>p<\/jats:italic> &lt; 0.05). Processes\/pathways potentially influenced by global changes, and function of these eight genes, suggest neurocognitive effects. Human observational and randomized controlled trial data were interrogated for translation. Methylation at birth was inversely associated with maternal plasma folate in six genes (\u22121.15% to \u22120.16% per nmol L<jats:sup>\u22121<\/jats:sup>; <jats:italic>p<\/jats:italic> &lt; 0.05), while maternal folic acid supplementation was associated with differential methylation of four genes in adulthood. Three CpGs were persistently hypermethylated with lower maternal folate (<jats:italic>p<\/jats:italic> = 0.04).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Some persistent folate\u2010induced methylation changes in mice are mirrored in humans. This demonstrates utility of mouse data in identifying human loci for interrogation as biomarkers of later\u2010life health.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.202100789","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T07:10:54Z","timestamp":1638342654000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Impact of In Utero Folate Exposure on DNA Methylation and Its Potential Relevance for Later\u2010Life Health\u2014Evidence from Mouse Models Translated to Human Cohorts"],"prefix":"10.1002","volume":"66","author":[{"given":"Dieuwertje E.","family":"Kok","sequence":"first","affiliation":[{"name":"Division of Human Nutrition and Health Wageningen University &amp; Research  Wageningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca C.","family":"Richmond","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit, Population Health Sciences Bristol Medical School University of Bristol  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel","family":"Adriaens","sequence":"additional","affiliation":[{"name":"Maastricht Centre for Systems Biology Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris T.","family":"Evelo","sequence":"additional","affiliation":[{"name":"Maastricht Centre for Systems Biology Maastricht University  Maastricht The Netherlands"},{"name":"Department of Bioinformatics \u2013 BiGCaT NUTRIM Research School Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianne","family":"Ford","sequence":"additional","affiliation":[{"name":"Department of Applied Sciences Faculty of Health and Life Sciences Northumbria University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Mathers","sequence":"additional","affiliation":[{"name":"Centre for Healthier Lives Population Health Sciences Institute Newcastle University Human Nutrition Research Centre  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natassia","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2711-0301","authenticated-orcid":false,"given":"Jill A.","family":"McKay","sequence":"additional","affiliation":[{"name":"Department of Applied Sciences Faculty of Health and Life Sciences Northumbria University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,13]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2007.01809.x"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare5010014"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0708473"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2016.11.011"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/gps.5138"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1809471115"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4020-9173-5_13"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3142"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.2011.02278.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31014"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2011.09.004"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30312-X"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-016-3452-1"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0029665108008744"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/15648265080292S114"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-020-00161-2"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.13574"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-44794-z"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201604-0788OC"},{"key":"e_1_2_9_20_1","first-page":"208","volume":"26","author":"Caffrey A.","year":"2018","journal-title":"Proc. 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