Telethon Kids Institute, The University of Western Australia, Perth, Australia
Alexander N Larcombe
Respiratory Environmental Health, Wal-yan Respiratory Research Centre, Telethon Kids Institute, Nedlands, Australia; Occupation, Environment and Safety, School of Population Health, Curtin University, Perth, Australia
Nina Kresoje
Telethon Kids Institute, Nedlands, Australia
Emily K Chivers
Respiratory Environmental Health, Wal-yan Respiratory Research Centre, Telethon Kids Institute, Nedlands, Australia
Chloe Bakker
Respiratory Environmental Health, Wal-yan Respiratory Research Centre, Telethon Kids Institute, Nedlands, Australia
James P Fitzpatrick
School of Psychological Sciences, University of Western Australia, Perth, Australia
Elizabeth J Elliott
University of Sydney, Faculty of Medicine and Health, Specialty of Child and Adolescent Health, Melbourne, Australia; Sydney Children’s Hospitals Network (Westmead) and Kids Research, Geelong, Australia
Deakin University, IMPACT – the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Australia; Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, Australia; Department of Paediatrics, University of Melbourne, Royal Children’s Hospital, Parkville, Australia
Evelyne Muggli
Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, Australia; Department of Paediatrics, University of Melbourne, Royal Children’s Hospital, Parkville, Australia
Jane Halliday
Department of Paediatrics, University of Melbourne, Royal Children’s Hospital, Parkville, Australia; Reproductive Epidemiology, Murdoch Children's Research Institute, Parkville, Australia
Delyse Hutchinson
Reproductive Epidemiology, Murdoch Children's Research Institute, Parkville, Australia; Deakin University, School of Psychology, Faculty of Health, Geelong, Australia; Murdoch Children’s Research Institute, Centre for Adolescent Health, Royal Children’s Hospital, Melbourne, Australia; University New South Wales, National Drug and Alcohol Research Centre, Sydney, Australia
Telethon Kids Institute, Nedlands, Australia; Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Australia; ARC Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Perth, Australia
Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Australia; ARC Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Perth, Australia
Martyn Symons
Telethon Kids Institute, The University of Western Australia, Perth, Australia; National Drug Research Institute, enAble Institute, Curtin University, Perth, Australia
Alcohol consumption in pregnancy can affect genome regulation in the developing offspring but results have been contradictory. We employed a physiologically relevant murine model of short-term moderate prenatal alcohol exposure (PAE) resembling common patterns of alcohol consumption in pregnancy in humans. Early moderate PAE was sufficient to affect site-specific DNA methylation in newborn pups without altering behavioural outcomes in adult littermates. Whole-genome bisulfite sequencing of neonatal brain and liver revealed stochastic influence on DNA methylation that was mostly tissue-specific, with some perturbations likely originating as early as gastrulation. DNA methylation differences were enriched in non-coding genomic regions with regulatory potential indicative of broad effects of alcohol on genome regulation. Replication studies in human cohorts with fetal alcohol spectrum disorder suggested some effects were metastable at genes linked to disease-relevant traits including facial morphology, intelligence, educational attainment, autism, and schizophrenia. In our murine model, a maternal diet high in folate and choline protected against some of the damaging effects of early moderate PAE on DNA methylation. Our studies demonstrate that early moderate exposure is sufficient to affect fetal genome regulation even in the absence of overt phenotypic changes and highlight a role for preventative maternal dietary interventions.
