Advanced search
Publication Cover
Epigenomics Volume 5, 2013 - Issue 1
Submit an article Journal homepage
248
Views
1
CrossRef citations to date
0
Altmetric
Review

Epigenetic Medicine and Fetal Alcohol Spectrum Disorders

Marisol Resendiz1 Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USAView further author information
,
Yuanyuan Chen2 Department of Anatomy & Cell Biology, MS508, Indiana University School Medicine, Indianapolis, IN 46202, USAView further author information
,
Nail C Öztürk2 Department of Anatomy & Cell Biology, MS508, Indiana University School Medicine, Indianapolis, IN 46202, USA;3 Department of Anatomy, Mersin University School of Medicine, TurkeyView further author information
&
Feng C Zhou1 Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA;2 Department of Anatomy & Cell Biology, MS508, Indiana University School Medicine, Indianapolis, IN 46202, USACorrespondence[email protected]
View further author information
Pages 73-86 | Published online: 15 Feb 2013

References

  • Heijmans BT , TobiEW, SteinAD et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc. Natl Acad. Sci. USA 105(44) , 17046–17049 (2008).
  • Suderman M , McgowanPO, SasakiA et al. Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus. Proc. Natl Acad. Sci. USA 109(Suppl. 2) , 17266–17272 (2012).
  • Madrigano J , BaccarelliA, MittlemanMA et al. Prolonged exposure to particulate pollution, genes associated with glutathione pathways, and DNA methylation in a cohort of older men. Environ. Health Perspect. 119(7) , 977–982 (2011).
  • Kumar A , ChoiKH, RenthalW et al. Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum. Neuron 48(2) , 303–314 (2005).
  • Zhang TY , HellstromIC, BagotRC, WenX, DiorioJ, MeaneyMJ. Maternal care and DNA methylation of a glutamic acid decarboxylase 1 promoter in rat hippocampus. J. Neurosci.30(39) , 13130–13137 (2010).
  • Little RE , SingCF. Father‘s drinking and infant birth weight: report of an association. Teratology36(1) , 59–65 (1987).
  • Hegedus AM , AltermanAI, TarterRE. Learning achievement in sons of alcoholics. Alcohol Clin. Exp. Res.8(3) , 330–333 (1984).
  • Ramsahoye BH , BiniszkiewiczD, LykoF, ClarkV, BirdAP, JaenischR. Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. Proc. Natl Acad. Sci. USA97(10) , 5237–5242 (2000).
  • Lister R , PelizzolaM, DowenRH et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462(7271) , 315–322 (2009).
  • Jones PA , TakaiD. The role of DNA methylation in mammalian epigenetics. Science293(5532) , 1068–1070 (2001).
  • Miranda TB , JonesPA. DNA methylation: the nuts and bolts of repression. J. Cell. Physiol.213(2) , 384–390 (2007).
  • Suzuki MM , BirdA. DNA methylation landscapes: provocative insights from epigenomics. Nat. Rev. Genet.9(6) , 465–476 (2008).
  • Ball MP , LiJB, GaoY et al. Targeted and genome-scale strategies reveal gene–body methylation signatures in human cells. Nat. Biotech. 27(4) , 361–368 (2009).
  • Anastasiadou C , MalousiA, MaglaverasN, KouidouS. Human epigenome data reveal increased CpG methylation in alternatively spliced sites and putative exonic splicing enhancers. DNA Cell Biol.30(5) , 267–275 (2011).
  • Bhutani N , DavidDM, BlauHM. DNA demethylation dynamics. Cell146(6) , 866–872 (2011).
  • Wu SC , ZhangY. Active DNA demethylation: many roads lead to Rome. Nat. Rev. Mol. Cell Biol.11(9) , 607–620 (2010).
  • Szulwach KE , LiX, LiY et al. 5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging. Nat. Neurosci. 14(12) , 1607–1616 (2011).
  • Song CX , SzulwachKE, FuY et al. Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine. Nat. Biotech. 29(1) , 68–72 (2011).
  • Kubiura M , OkanoM, KimuraH, KawamuraF, TadaM. Chromosome-wide regulation of euchromatin-specific 5mC to 5hmC conversion in mouse ES cells and female human somatic cells. Chromosome Res.20(7) , 837–848 (2012).
  • Inoue A , ZhangY. Replication-dependent loss of 5-hydroxymethylcytosine in mouse preimplantation embryos. Science334(6053) , 194 (2011).
  • Iqbal K , JinSG, PfeiferGP, SzaboPE. Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine. Proc. Natl Acad. Sci. USA108(9) , 3642–3647 (2011).
  • Wu H , D‘alessioAC, ItoS et al. Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells. Genes Dev. 25(7) , 679–684 (2011).
  • Pastor WA , PapeUJ, HuangY et al. Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells. Nature 473(7347) , 394–397 (2011).
  • Williams K , ChristensenJ, PedersenMT et al. TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature 473(7347) , 343–348 (2011).
  • Stroud H , FengS, Morey Kinney S, Pradhan S, Jacobsen SE. 5-hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells. Genome Biol.12(6) , R54 (2011).
  • Yildirim O , LiR, HungJH et al. Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells. Cell 147(7) , 1498–1510 (2011).
  • Morgan HD , SantosF, GreenK, DeanW, ReikW. Epigenetic reprogramming in mammals. Hum. Mol. Genet.14 Spec No 1 , R47–R58 (2005).
  • Salvaing J , Aguirre-LavinT, BoulesteixC, LehmannG, DebeyP, BeaujeanN. 5-Methylcytosine and 5-hydroxymethylcytosine spatiotemporal profiles in the mouse zygote. PLoS ONE7(5) , e38156 (2012).
  • Nestor CE , OttavianoR, ReddingtonJ et al. Tissue type is a major modifier of the 5-hydroxymethylcytosine content of human genes. Genome Res. 22(3) , 467–477 (2012).
  • Zhou FC , ChenY, LoveA. Cellular DNA methylation program during neurulation and its alteration by alcohol exposure. Birth Defects Res. A Clin. Mol. Teratol.91(8) , W703–W715 (2011).
  • Zhou F . DNA methylation program during development. Front. Biol.7(6) , 485–494 (2012).
  • Chen Y , ZhouFC. Alcohol alters cellular DNA methylation program in growth retarded cortex and hippocampus. Alcohol Clin. Exp. Res.36(Suppl. 1), Abstract 0789 (2012).
  • Ozturk N , ZhouFC. Alcohol markedly alters methyl binding proteins during neural development. Alcohol Clin. Exp. Res.36(Suppl. 1), Abstract 0459 (2012).
  • Liu Y , BalaramanY, WangG, NephewKP, ZhouFC. Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation. Epigenetics4(7) , 500–511 (2009).
  • Zhou FC , BalaramanY, TengM, LiuY, SinghRP, NephewKP. Alcohol alters DNA methylation patterns and inhibits neural stem cell differentiation. Alcohol Clin. Exp. Res.35(4) , 735–746 (2011).
  • Khare T , PaiS, KonceviciusK et al. 5-hmC in the brain is abundant in synaptic genes and shows differences at the exon-intron boundary. Nat. Struct. Mol. Biol. 19(10) , 1037–1043 (2012).
  • Niculescu MD , ZeiselSH. Diet, methyl donors and DNA methylation: interactions between dietary folate, methionine and choline. J. Nutr.132(8) , S2333–S2335 (2002).
  • Wani NA , NadaR, KaurJ. Biochemical and molecular mechanisms of folate transport in rat pancreas; interference with ethanol ingestion. PLoS ONE6(12) , e28599 (2011).
  • Biswas A , SenthilkumarSR, SaidHM. Effect of chronic alcohol exposure on folate uptake by liver mitochondria. Am. J. Physiol. Cell Physiol.302(1) , C203–C209 (2012).
  • Mcguffin R , GoffP, HillmanRS. The effect of diet and alcohol on the development of folate deficiency in the rat. Br. J. Haematol.31(2) , 185–192 (1975).
  • Hutson JR , StadeB, LehotayDC, CollierCP, KapurBM. Folic acid transport to the human fetus is decreased in pregnancies with chronic alcohol exposure. PLoS ONE7(5) , e38057 (2012).
  • Kharbanda KK . Alcoholic liver disease and methionine metabolism. Semin. Liver Dis.29(02) , 155–165 (2009).
  • Lu SC , Huang Z-Z, Yang H, Mato JM, Avila MA, Tsukamoto H. Changes in methionine adenosyltransferase and S-adenosylmethionine homeostasis in alcoholic rat liver. Am. J. Physiol. Gastrointest. Liver Physiol.279(1) , G178–G185 (2000).
  • Lee SJ , KangMH, MinH. Folic acid supplementation reduces oxidative stress and hepatic toxicity in rats treated chronically with ethanol. Nutr. Res. Pract.5(6) , 520–526 (2011).
  • Ojeda ML , BarreroMJ, NogalesF, MurilloML, CarrerasO. Oxidative effects of chronic ethanol consumption on the functions of heart and kidney: folic acid supplementation. Alcohol Alcohol.47(4) , 404–412 (2012).
  • Barrero MJ , OjedaML, Díaz Castro J, Nogales F, Murillo ML, Carreras O. The effects of ethanol upon hydric balance and arterial pressure in rats: folic acid as a possible hypotensor. Life Sci.90(9–10) , 337–342 (2012).
  • Chirapapaisan N , UiprasertkulM, ChuncharuneeA. The effect of coenzyme Q10 and curcumin on chronic methanol intoxication induced retinopathy in rats. J. Med. Assoc. Thai.95(Suppl. 4) , S76–S81 (2012).
  • Gundogan F , ElwoodG, MarkP et al. Ethanol-induced oxidative stress and mitochondrial dysfunction in rat placenta. Relevance to pregnancy loss. Alcohol Clin. Exp. Res. 34(3) , 415–423 (2010).
  • Liu YQ , LiuY, MoritaT, SugiyamaK. Methionine and serine synergistically suppress hyperhomocysteinemia induced by choline deficiency, but not by guanidinoacetic acid, in rats fed a low casein diet. Biosci. Biotechnol. Biochem.75(12) , 2333–2339 (2011).
  • Chen YL , YangSS, PengHC, HsiehYC, ChenJR, YangSC. Folate and vitamin B12 improved alcohol-induced hyperhomocysteinemia in rats. Nutrition27(10) , 1034–1039 (2011).
  • Blencowe H , CousensS, ModellB, LawnJ. Folic acid to reduce neonatal mortality from neural tube disorders. Int. J. Epidemiol.39(Suppl. 1) , I110–I121 (2010).
  • Safi J , JoyeuxL, ChalouhiGE. Periconceptional folate deficiency and implications in neural tube defects. J. Pregnancy2012 , 295083 (2012).
  • Yanaguita M , GutierrezC, RibeiroC, LimaG, MachadoH, PeresL. Pregnancy outcome in ethanol-treated mice with folic acid supplementation in saccharose. Childs Nerv. Syst.24(1) , 99–104 (2008).
  • Monk BR , LeslieFM, ThomasJD. The effects of perinatal choline supplementation on hippocampal cholinergic development in rats exposed to alcohol during the brain growth spurt. Hippocampus22(8) , 1750–1757 (2012).
  • Thomas JD , TranTD. Choline supplementation mitigates trace, but not delay, eyeblink conditioning deficits in rats exposed to alcohol during development. Hippocampus22(3) , 619–630 (2012).
  • Thomas JD , IdrusNM, MonkBR, DominguezHD. Prenatal choline supplementation mitigates behavioral alterations associated with prenatal alcohol exposure in rats. Birth Defects Res. A Clin. Mol. Teratol.88(10) , 827–837 (2010).
  • Ryan SH , WilliamsJK, ThomasJD. Choline supplementation attenuates learning deficits associated with neonatal alcohol exposure in the rat: effects of varying the timing of choline administration. Brain Res.1237 , 91–100 (2008).
  • Niculescu MD , CraciunescuCN, ZeiselSH. Dietary choline deficiency alters global and gene-specific DNA methylation in the developing hippocampus of mouse fetal brains. FASEB J.20(1) , 43–49 (2006).
  • Kovacheva VP , MellottTJ, DavisonJM et al. Gestational choline deficiency causes global and Igf2 gene DNA hypermethylation by up-regulation of Dnmt1 expression. J. Biol. Chem. 282(43) , 31777–31788 (2007).
  • Davison JM , MellottTJ, KovachevaVP, BlusztajnJK. Gestational choline supply regulates methylation of histone H3, expression of histone methyltransferases G9a (Kmt1c) and Suv39h1 (Kmt1a), and DNA methylation of their genes in rat fetal liver and brain. J. Biol. Chem.284(4) , 1982–1989 (2009).
  • Soliman M , RosenbergerT. Acetate supplementation increases brain histone acetylation and inhibits histone deacetylase activity and expression. Mol. Cell. Biochem.352(1) , 173–180 (2011).
  • Kenyon SH , NicolaouA, GibbonsWA. The effect of ethanol and its metabolites upon methionine synthase activity in vitro. Alcohol15(4) , 305–309 (1998).
  • Garro AJ , McbethDL, LimaV, LieberCS. Ethanol consumption inhibits fetal DNA methylation in mice: implications for the fetal alcohol syndrome. Alcohol Clin. Exp. Res.15(3) , 395–398 (1991).
  • Wolff GL , KodellRL, MooreSR, CooneyCA. Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice. FASEB J.12(11) , 949–957 (1998).
  • Duhl DM , VrielingH, MillerKA, WolffGL, BarshGS. Neomorphic agouti mutations in obese yellow mice. Nat. Genet.8(1) , 59–65 (1994).
  • Kaminen-Ahola N , AholaA, MagaM et al. Maternal ethanol consumption alters the epigenotype and the phenotype of offspring in a mouse model. PLoS Genet. 6(1) , e1000811 (2010).
  • Ouko LA , ShantikumarK, KnezovichJ, HaycockP, SchnughDJ, RamsayM. Effect of alcohol consumption on CpG methylation in the differentially methylated regions of H19 and IG-DMR in male gametes-implications for fetal alcohol spectrum disorders. Alcohol Clin. Exp. Res.33(9) , 1615–1627 (2009).
  • Haycock PC . Fetal alcohol spectrum disorders: the epigenetic perspective. Biol. Reprod.81(4) , 607–617 (2009).
  • Marutha Ravindran CR , TickuMK. Changes in methylation pattern of NMDA receptor NR2B gene in cortical neurons after chronic ethanol treatment in mice. Brain Res. Mol. Brain Res.121(1–2) , 19–27 (2004).
  • Govorko D , BekdashRA, ZhangC, SarkarDK. Male germline transmits fetal alcohol adverse effect on hypothalamic proopiomelanocortin gene across generations. Biol. Psychiatry72(5) , 378–388 (2012).
  • Otero NK , ThomasJD, SaskiCA, XiaX, KellySJ. Choline supplementation and DNA methylation in the hippocampus and prefrontal cortex of rats exposed to alcohol during development. Alcohol Clin. Exp. Res.36(10) , 1701–1709 (2012).
  • Zhou F . DNA Methylation program during development. Front. Biol.7(6) , 485–494 (2012).
  • Kim JS , ShuklaSD. Acute in vivo effect of ethanol (binge drinking) on histone H3 modifications in rat tissues. Alcohol Alcohol.41(2) , 126–132 (2006).
  • Shukla SD , LeeYJ, ParkPH, AroorAR. Acetaldehyde alters MAP kinase signalling and epigenetic histone modifications in hepatocytes. In: Acetaldehyde-Related Pathology: Bridging the Trans-Disciplinary Divide. Chadwick DJ, Goode J (Eds). John Wiley & Sons, Ltd, NJ, USA, 217–228 (2007).
  • Pal-Bhadra M , BhadraU, JacksonDE, MamathaL, Park P-H, Shukla SD. Distinct methylation patterns in histone H3 at Lys-4 and Lys-9 correlate with up- & down-regulation of genes by ethanol in hepatocytes. Life Sci.81(12) , 979–987 (2007).
  • D‘Addario C , CaputiF, EkströmT et al. Ethanol induces epigenetic modulation of prodynorphin and pronociceptin gene expression in the rat amygdala complex. J. Mol. Neurosci. 49(2) , 312–319 (2012).
  • Guo W , CrosseyEL, ZhangL et al. Alcohol exposure decreases CREB binding protein expression and histone acetylation in the developing cerebellum. PLoS ONE 6(5) , e19351 (2011).
  • D‘addario C , JohanssonS, CandelettiS et al. Ethanol and acetaldehyde exposure induces specific epigenetic modifications in the prodynorphin gene promoter in a human neuroblastoma cell line. FASEB J. 25(3) , 1069–1075 (2011).
  • Xiangyuan W ang, Gomutputra P, Wolgemuth DJ, Baxi LV. Acute alcohol exposure induces apoptosis and increases histone H3K9/18 acetylation in the mid-gestation mouse lung. Reprod. Sci.17(4) , 384–390 (2010).
  • Jiang X , YanJ, WestAA et al. Maternal choline intake alters the epigenetic state of fetal cortisol-regulating genes in humans. FASEB J. 26(8) , 3563–3574 (2012).
  • Wang LL , ZhangZ, LiQ et al. Ethanol exposure induces differential microRNA and target gene expression and teratogenic effects which can be suppressed by folic acid supplementation. Hum. Reprod. 24(3) , 562–579 (2009).
  • Miranda R . MicroRNAs and fetal brain development: implications for ethanol teratology during the second trimester period of neurogenesis. Front. Genet.3 , 77 (2012).
  • Soares AR , PereiraPM, FerreiraV et al. Ethanol exposure induces upregulation of specific microRNAs in zebrafish embryos. Toxicol. Sci. 127(1) , 18–28 (2012).
  • Shibata M , NakaoH, KiyonariH, AbeT, AizawaS. MicroRNA-9 regulates neurogenesis in mouse telencephalon by targeting multiple transcription factors. J. Neurosci.31(9) , 3407–3422 (2011).
  • Fabbri M , GarzonR, CimminoA et al. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc. Natl Acad. Sci. USA 104(40) , 15805–15810 (2007).
  • Baer C , ClausR, FrenzelLP et al. Extensive promoter DNA hypermethylation and hypomethylation is associated with aberrant microRNA Expression in chronic lymphocytic leukemia. Cancer Res. 72(15) , 3775–3785 (2012).
  • Wilhelm-Benartzi CS , HousemanEA, MaccaniMA et al. In utero exposures, infant growth, and DNA methylation of repetitive elements and developmentally related genes in human placenta. Environ. Health Perspect.120(2) , 296–302 (2012).
  • Haycock PC , RamsayM. Exposure of mouse embryos to ethanol during preimplantation development: effect on DNA methylation in the H19 imprinting control region. Biol. Reprod.81(4) , 618–627 (2009).
  • Downing C , JohnsonTE, LarsonC et al. Subtle decreases in DNA methylation and gene expression at the mouse Igf2 locus following prenatal alcohol exposure. effects of a methyl-supplemented diet. Alcohol 45(1) , 65–71 (2011).
  • Rubert G , MiñanaR, PascualM, GuerriC. Ethanol exposure during embryogenesis decreases the radial glial progenitor pool and affects the generation of neurons and astrocytes. J. Neurosci. Res.84(3) , 483–496 (2006).
  • Miller MW . Migration of cortical neurons is altered by gestational exposure to ethanol. Alcohol Clin. Exp. Res.17(2) , 304–314 (1993).
  • Roitbak T , ThomasK, MartinA, AllanA, CunninghamLA. Moderate fetal alcohol exposure impairs neurogenic capacity of murine neural stem cells isolated from the adult subventricular zone. Exp. Neurol.229(2) , 522–525 (2011).
  • De La Monte SM , GanjuN, BanerjeeK, BrownNV, LuongT, WandsJR. Partial rescue of ethanol-induced neuronal apoptosis by growth factor activation of phosphoinositol-3-kinase. Alcohol Clin. Exp. Res.24(5) , 716–726 (2000).
  • Goh JM , BensleyJG, KennaK et al. Alcohol exposure during late gestation adversely affects myocardial development with implications for postnatal cardiac function. Am. J. Physiol. Heart Circ. Physiol. 300(2) , H645–H651 (2011).
  • Parnell SE , DehartDB, WillsTA et al. Maternal oral intake mouse model for fetal alcohol spectrum disorders: ocular defects as a measure of effect. Alcohol Clin. Exp. Res. 30(10) , 1791–1798 (2006).
  • Hofer R , BurdL. Review of published studies of kidney, liver, and gastrointestinal birth defects in fetal alcohol spectrum disorders. Birth Defects Res. A Clin. Mol. Teratol.85(3) , 179–183 (2009).
  • Burd L , KlugMG, MartsolfJT, KerbeshianJ. Fetal alcohol syndrome: neuropsychiatric phenomics. Neurotoxicol. Teratol.25(6) , 697–705 (2003).
  • Connor PD , SampsonPD, StreissguthAP, BooksteinFL, BarrHM. Effects of prenatal alcohol exposure on fine motor coordination and balance: a study of two adult samples. Neuropsychologia44(5) , 744–751 (2006).
  • Mattson SN , RoebuckTM. Acquisition and retention of verbal and nonverbal information in children with heavy prenatal alcohol exposure. Alcohol Clin. Exp. Res.26(6) , 875–882 (2002).
  • Mattson SN , GoodmanAM, CaineC, DelisDC, RileyEP. Executive functioning in children with heavy prenatal alcohol exposure. Alcohol Clin. Exp. Res.23(11) , 1808–1815 (1999).
  • Famy C , StreissguthAP, UnisAS. Mental illness in adults with fetal alcohol syndrome or fetal alcohol effects. Am. J. Psychiatry155(4) , 552–554 (1998).
  • O‘Connor M , ShahB, WhaleyS, CroninP, GundersonB, GrahamJ. Psychiatric illness in a clinical sample of children with prenatal alcohol exposure. Am. J. Drug Alcohol Abuse28(4) , 743 (2002).
  • Hamid A , WaniNA, KaurJ. New perspectives on folate transport in relation to alcoholism-induced folate malabsorption – association with epigenome stability and cancer development. FEBS J.276(8) , 2175–2191 (2009).
  • Shukla SD , VelazquezJ, FrenchSW, LuSC, TickuMK, ZakhariS. Emerging role of epigenetics in the actions of alcohol. Alcohol Clin. Exp. Res.32(9) , 1525–1534 (2008).
  • Walker AK , NakamuraT, ByrneRJ et al. Neonatal lipopolysaccharide and adult stress exposure predisposes rats to anxiety-like behaviour and blunted corticosterone responses. Implications for the double-hit hypothesis. Psychoneuroendocrinology 34(10) , 1515–1525 (2009).
  • Kirkbride JB , SusserE, KundakovicM, KresovichJK, Davey Smith G, Relton CL. Prenatal nutrition, epigenetics and schizophrenia risk: can we test causal effects? Epigenomics4(3) , 303–315 (2012).
  • Sabunciyan S , AryeeMJ, IrizarryRA et al. Genome-wide DNA methylation scan in major depressive disorder. PLoS ONE 7(4) , e34451 (2012).
  • Seitz HK , StickelF. Molecular mechanisms of alcohol-mediated carcinogenesis. Nat. Rev. Cancer7(8) , 599–612 (2007).
  • Walsh C , MacmillanHL, JamiesonE. The relationship between parental substance abuse and child maltreatment: findings from the Ontario Health Supplement. Child Abuse Negl.27(12) , 1409–1425 (2003).
  • Branchi I , KarpovaNN, D‘AndreaI, CastrénE, AllevaE. Epigenetic modifications induced by early enrichment are associated with changes in timing of induction of BDNF expression. Neurosci. Lett.495(3) , 168–172 (2011).
  • Anway MD , RekowSS, SkinnerMK. Comparative anti-androgenic actions of vinclozolin and flutamide on transgenerational adult onset disease and spermatogenesis. Reprod. Toxicol.26(2) , 100–106 (2008).
  • Crépin M , DieuMC, LejeuneS et al. Evidence of constitutional MLH1 epimutation associated to transgenerational inheritance of cancer susceptibility. Hum Mutat. 33(1) , 180–188 (2012).
  • Bielawski DM , ZaherFM, SvinarichDM, AbelEL. Paternal alcohol exposure affects sperm cytosine methyltransferase messenger RNA levels. Alcohol Clin. Exp. Res.26(3) , 347–351 (2002).
  • Knezovich JG , RamsayM. The effect of preconception paternal alcohol exposure on epigenetic remodelling of the H19 and Rasgrf1 imprinting control regions in mouse offspring. Front. Genet.3 , 10 (2012).
  • Stouder C , SommE, Paoloni-GiacobinoA. Prenatal exposure to ethanol: a specific effect on the H19 gene in sperm. Reprod. Toxicol.31(4) , 507–512 (2011).
  • Cisneros FJ , BranchS. Transplacental exposure to the DNA demethylating agent, 5-AZA-CdR, affects the sexual behavior of CD-1 male mice. Neuroyoxicology25(3) , 411–417 (2004).
  • Zimmermann U , SpringK, WittchenHU et al. Arginine vasopressin and adrenocorticotropin secretion in response to psychosocial stress is attenuated by ethanol in sons of alcohol-dependent fathers. J. Psychiatr. Res. 38(4) , 385–393 (2004).
  • Ueno M , KatayamaKI, NakayamaH, DoiK. Mechanisms of 5-azacytidine (5AzC)-induced toxicity in the rat foetal brain. Int. J. Exp. Pathol.83(3) , 139–150 (2002).
  • Li J , LiXM, CaudillM et al. Betaine feeding prevents the blood alcohol cycle in rats fed alcohol continuously for 1 month using the rat intragastric tube feeding model. Exp. Mol. Pathol. 91(2) , 540–547 (2011).
  • A Report of the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline and Subcommittee on Upper Reference Levels of Nutrients, Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. The National Academies Press, Washington, DC, USA (1998).
  • Feinberg AP . Epigenetics at the epicenter of modern medicine. JAMA299(11) , 1345–1350 (2008).
  • Halsted CH , VillanuevaJ, ChandlerCJ et al. Ethanol feeding of micropigs alters methionine metabolism and increases hepatocellular apoptosis and proliferation. Hepatology 23(3) , 497–505 (1996).
  • Bönsch D , LenzB, FiszerR, FrielingH, KornhuberJ, BleichS. Lowered DNA methyltransferase (DNMT-3b) mRNA expression is associated with genomic DNA hypermethylation in patients with chronic alcoholism. J. Neural Transm.113(9) , 1299–1304 (2006).
  • Ehrlich D , PirchlM, HumpelC. Effects of long-term moderate ethanol and cholesterol on cognition, cholinergic neurons, inflammation, and vascular impairment in rats. Neuroscience205 , 154–166 (2012).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.