Table 2.

Summary of the Epigenetic Effects of Alcohol on Early Development

Age	Model	EtOH Dose or BEC	Cell Type	Effects	Citation
Fetal	Cultured rat fetal astrocytes	75 mM	Cultured astrocytes	Decreased DNMT activity, decreased methylation of tPA promoter, decreased DNMT3a protein	Zhang et al., 2014
Fetal	Cultured mouse fetal cortical neurons	75 mM, 5 days	Cultured neurons	Demethylation of NR2B gene	Marutha Ravindran & Ticku, 2004
Fetal	Cultured mouse fetal cortical neurons	75 mM, 5 days for chronic intermittent ethanol paradigm	Cultured neurons	Demethylation of NR2B gene	Qiang et al., 2010
Fetal	Mouse, cultured embryo	Dose: 88 mM	Cultured embryo	Altered methylation in many genes involved in metabolism, neural development, imprinting	Liu et al., 2009
Fetal	Mouse, cultured neurospheres	Dose: 13 mM, 26 mM, 70 mM	Cultured neurospheres	Altered activating and repressive histone marks (H3K4me3 and H3K27me3) on genes involved in neural precursor identity and neurogenesis	Veazey et al., 2013
Fetal	Cultured mouse fetal cortical neurospheres	13 mM or 70 mM EtOH	Cultured neurospheres	High dose suppressed miR-21, -335, -9, and -153; Low dose increased miR-335	Sathyan et al., 2007
Fetal	Mouse, Gestational day 9–11	Dose: 3 g/kg	Somatic embryo	DNA hypomethylation, lower methylase activity	Garro et al., 1991
Fetal	Mice, Gestational day 9	Dose: 5.8 g/kg EtOH	Somatic embryo	Subtle decrease in methylation of Igf2 locus with EtOH	Downing et al., 2011
Fetal	Mouse, Gestational day 6–15	BEC: ≥0.4 μg/mL EtOH	Brain	Upregulation of many miRNAs, including, miR-10a, miR-10b, miR-9 with EtOH; Downregulation of many miRNAs, including miR-200a, miR-496, miR-296 with EtOH	Wang et al., 2009
Fetal	Mouse, Gestational Day 0.5–8.5	Dose: ~12 g/kg/day	Brain (hippocampus)	Altered miRNAs expression of miR138-2, miR290, miR16-2; Altered site specific methylation of several CpG islands	Marjonen et al., 2015
Fetal	Mouse and Rat, Gestational day 6–15	Dose: 0.5, 1, 2, 4 and 6 g/kg/day	Brain	Decreased MeCP2 in prefrontal cortex and striatum	Kim et al., 2013
Fetal	Rat, Gestational day 8–21	Dose: 5% w/v EtOH, 35% ethanol-derived calories	Brain (hippocampus and cortex)	Altered imprinting patterns and expression of Dio3	Sittig et al., 2011
Fetal	Mouse, Gestational day 7–16	BEC: 120–160 mg/dL	Brain (hippocampus)	Altered methylation program during development in hippocampus, decreased Mecp2 and Tet1	Chen et al., 2013
Fetal	Rats, Gestational day 7–21	Dose: 6.7% EtOH (v/v), BEC: ~110–120 mg/dL	Brain (hypothalamus) in Pomc cells	Increased MeCP2 protein and DNA binding to Pomc gene	Gangisetty et al., 2014
Neonatal	Rats, postnatal days 2–12	BEC: 30–80 mM	Brain (cerebellum)	Reduced CREB binding protein, reduced H3 and H4 acetylation with EtOH exposure	Guo et al., 2011
Fetal and preconception	Mouse; Fetal: gestational Day 0.5–8.5; Preconception: 4 days/week for 10 weeks	Dose: 10% EtOH (v/v), ~12 g/kg/day	Tail	Hypermethylation of the Agouti mutation (Avy) locus and transcriptional silencing of the gene	Kaminen-Ahola et al., 2010
Fetal (F1) exposure, F1–3 generations	Rats, Gestational day 7–21	Dose: 6.7% EtOH (v/v), BEC: ~110–120 mg/dL	Brain (hypothalamic neurons), sperm	Increased methylation of the Pomc gene promoter in hypothalamus and sperm cells in F1-F3 offspring	Govorko et al., 2012; Bekdash et al., 2013
Fetal (F1) exposure, F2 offspring	Mouse, Gestational day 10–18	Dose: 0.5 g/kg/day EtOH	Sperm, brain	Decrease in methylation of H19 gene in sperm of exposed F1 offspring, Decrease in methylation of H19 gene in brain of F2 offspring	Stouder et al., 2011
Human children	Human children with FASD and healthy control children	Not reported	Buccal epithelial cells	658 differentially methylated sites in FASD children compared to controls, overlapping with 95 different genes; increased methylation on genes relevant to neurodevelopment	Portales-Casamar et al., 2016