Pre-implantation alcohol exposure induces lasting sex-specific DNA methylation programming errors in the developing forebrain
| Autor: | Anthony Lemieux, Maxime Caron, Serge McGraw, Karine Doiron, Loydie A. Jerome-Majewska, Lisa-Marie Legault, Daniel Sinnett, Alexandra Langford-Avelar, Mélanie Breton-Larrivée |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Alcohol Drinking Embryonic Development Biology Bioinformatics Epigenesis Genetic Biological pathway Mice Prosencephalon Pregnancy Prenatal exposure Early embryonic development Genetics Animals Humans Imprinting (psychology) Molecular Biology Genetics (clinical) Fetus DNA methylation Research Gene Expression Regulation Developmental Imprinting Phenotype Embryonic stem cell Human genetics Disease Models Animal Fetal alcohol spectrum disorder Epigenetic reprogramming Fetal Alcohol Spectrum Disorders Prenatal Exposure Delayed Effects Forebrain Female Reprogramming Developmental Biology DNA Damage |
| Zdroj: | Clinical Epigenetics |
| ISSN: | 1868-7083 |
| Popis: | Background Prenatal alcohol exposure is recognized for altering DNA methylation profiles of brain cells during development, and to be part of the molecular basis underpinning Fetal Alcohol Spectrum Disorder (FASD) etiology. However, we have negligible information on the effects of alcohol exposure during pre-implantation, the early embryonic window marked with dynamic DNA methylation reprogramming, and on how this may rewire the brain developmental program. Results Using a pre-clinical in vivo mouse model, we show that a binge-like alcohol exposure during pre-implantation at the 8-cell stage leads to surge in morphological brain defects and adverse developmental outcomes during fetal life. Genome-wide DNA methylation analyses of fetal forebrains uncovered sex-specific alterations, including partial loss of DNA methylation maintenance at imprinting control regions, and abnormal de novo DNA methylation profiles in various biological pathways (e.g., neural/brain development). Conclusion These findings support that alcohol-induced DNA methylation programming deviations during pre-implantation could contribute to the manifestation of neurodevelopmental phenotypes associated with FASD. |
| Databáze: | OpenAIRE |
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