RT Journal Article
SR Electronic
T1 Pre-Implantation Alcohol Exposure Induces Lasting Sex-Specific DNA Methylation Programming Errors in the Developing Forebrain
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.07.415208
DO 10.1101/2020.12.07.415208
A1 LM Legault
A1 K Doiron
A1 M Breton-Larrivée
A1 A Langford-Avelar
A1 A Lemieux
A1 M Caron
A1 LA Jerome-Majewska
A1 D Sinnett
A1 S McGraw
YR 2021
UL http://biorxiv.org/content/early/2021/08/11/2020.12.07.415208.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.