Pre-implantation alcohol exposure induces lasting sex-specific DNA methylation programming errors in the developing forebrain

Clinical Epigenetics

M. Caron¹  K. Doiron¹  L. M. Legault²  M. Breton-Larrivée²  A. Lemieux²  A. Langford-Avelar²  S. McGraw³  D. Sinnett⁴  L. A. Jerome-Majewska⁵ 

[1] CHU Sainte-Justine Research Center, 3175 Chemin de La Côte-Sainte-Catherine, H3T 1C5, Montréal, QC, Canada;CHU Sainte-Justine Research Center, 3175 Chemin de La Côte-Sainte-Catherine, H3T 1C5, Montréal, QC, Canada;Department of Biochemistry and Molecular Medicine, Université de Montréal, 2900 Boulevard Edouard-Montpetit, H3T 1J4, Montréal, QC, Canada;CHU Sainte-Justine Research Center, 3175 Chemin de La Côte-Sainte-Catherine, H3T 1C5, Montréal, QC, Canada;Department of Biochemistry and Molecular Medicine, Université de Montréal, 2900 Boulevard Edouard-Montpetit, H3T 1J4, Montréal, QC, Canada;Department of Obstetrics and Gynecology, Université de Montréal, 2900 Boulevard Edouard-Montpetit, H3T 1J4, Montréal, QC, Canada;CHU Sainte-Justine Research Center, 3175 Chemin de La Côte-Sainte-Catherine, H3T 1C5, Montréal, QC, Canada;Department of Pediatrics, Université de Montréal, 2900 Boulevard Edouard-Montpetit, H3T 1J4, Montréal, QC, Canada;McGill University Health Centre Glen Site, 1001 Boulevard Décarie, H4A 3J1, Montréal, QC, Canada;Department of Pediatrics, McGill University, 1001 Boulevard Décarie, H4A 3J1, Montréal, QC, Canada;

关键词: Prenatal exposure;    Fetal alcohol spectrum disorder;    DNA methylation;    Early embryonic development;    Epigenetic reprogramming;    Imprinting;   

DOI  :  10.1186/s13148-021-01151-0

来源: Springer

【 摘 要 】

BackgroundPrenatal 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.ResultsUsing 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).ConclusionThese findings support that alcohol-induced DNA methylation programming deviations during pre-implantation could contribute to the manifestation of neurodevelopmental phenotypes associated with FASD.

【 授权许可】

CC BY