{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:30:45Z","timestamp":1790753445105,"version":"4.1.0"},"reference-count":102,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["U01 AA026101"],"award-info":[{"award-number":["U01 AA026101"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R37 AA007789"],"award-info":[{"award-number":["R37 AA007789"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R01 AA022460"],"award-info":[{"award-number":["R01 AA022460"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015741","name":"Kids Brain Health Network","doi-asserted-by":"publisher","award":["Grant"],"award-info":[{"award-number":["Grant"]}],"id":[{"id":"10.13039\/501100015741","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009408","name":"Brain Canada Foundation","doi-asserted-by":"publisher","award":["Developmental Neurosciences Research Training Award"],"award-info":[{"award-number":["Developmental Neurosciences Research Training Award"]}],"id":[{"id":"10.13039\/100009408","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Prenatal adversity or stress can have long-term consequences on developmental trajectories and health outcomes. Although the biological mechanisms underlying these effects are poorly understood, epigenetic modifications, such as DNA methylation, have the potential to link early-life environments to alterations in physiological systems, with long-term functional implications. We investigated the consequences of two prenatal insults, prenatal alcohol exposure (PAE) and food-related stress, on DNA methylation profiles of the rat brain during early development. As these insults can have sex-specific effects on biological outcomes, we analyzed epigenome-wide DNA methylation patterns in prefrontal cortex, a key brain region involved in cognition, executive function, and behavior, of both males and females. We found sex-dependent and sex-concordant influences of these insults on epigenetic patterns. These alterations occurred in genes and pathways related to brain development and immune function, suggesting that PAE and food-related stress may reprogram neurobiological\/physiological systems partly through central epigenetic changes, and may do so in a sex-dependent manner. Such epigenetic changes may reflect the sex-specific effects of prenatal insults on long-term functional and health outcomes and have important implications for understanding possible mechanisms underlying fetal alcohol spectrum disorder and other neurodevelopmental disorders.<\/jats:p>","DOI":"10.3390\/genes12111773","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T12:46:23Z","timestamp":1636461983000},"page":"1773","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Prenatal Adversity Alters the Epigenetic Profile of the Prefrontal Cortex: Sexually Dimorphic Effects of Prenatal Alcohol Exposure and Food-Related Stress"],"prefix":"10.3390","volume":"12","author":[{"given":"Alexandre A.","family":"Lussier","sequence":"first","affiliation":[{"name":"Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA"},{"name":"Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7301-5700","authenticated-orcid":false,"given":"Tamara S.","family":"Bodnar","sequence":"additional","affiliation":[{"name":"Department of Cellular and Physiological Sciences, Faculty of Medicine, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Moksa","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hirst","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada"},{"name":"Canada\u2019s Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 4S6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Kobor","sequence":"additional","affiliation":[{"name":"BC Children\u2019s Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada"},{"name":"Department of Medical Genetics, University of British Columbia, Vancouver, BC V5Z 4H4, Canada"},{"name":"Centre for Molecular Medicine and Therapeutics, Vancouver, BC V5Z 4H4, Canada"},{"name":"Program in Child and Brain Development, CIFAR, MaRS Centre, West Tower, 661 University Ave., Suite 505, Toronto, ON M5G 1M1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7937-3904","authenticated-orcid":false,"given":"Joanne","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Department of Cellular and Physiological Sciences, Faculty of Medicine, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.3389\/fpsyg.2010.00223","article-title":"Prenatal Maternal Stress Associated with ADHD and Autistic Traits in Early Childhood","volume":"1","author":"Ronald","year":"2011","journal-title":"Front. 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