The Dysfunctional Placenta Epigenome: Causes and Consequences

• Murr R . Interplay between different epigenetic modifications and mechanisms. Adv. Genet.70 , 101–141 (2010).
   PubMed Web of Science ®Google Scholar
• Fowden AL , MooreT. Review: parent–offspring conflict and the control of placental function. Placenta33(Suppl. 33) , S33–S36 (2012).
   PubMed Web of Science ®Google Scholar
• Frost JM , MooreGE. The importance of imprinting in the human placenta. PLoS Genet.6 , e1001015 (2010).
   PubMed Web of Science ®Google Scholar
• Fowden AL , CoanPL, AngioliniE, BurtonGJ, ConstanciaM. Imprinted genes and the epigenetic regulation of placental phenotype. Prog. Biophys. Mol. Bio.106(1) , 281–288 (2011).
   PubMed Web of Science ®Google Scholar
• Chiu RW , ChimSS, WongIHet al. Hypermethylation of RASSF1A in human and rhesus placentae. Am. J. Pathol. 170(3) , 941–950 (2007).
   PubMed Web of Science ®Google Scholar
• Wong NC , NovakovicB, WeinrichBet al. Methylation of the adenomatous polyposis coli (APC) gene in human placenta and hypermethylation in choriocarcinoma cells. Cancer Lett. 268(1) , 56-62 (2008).
   PubMed Web of Science ®Google Scholar
• Cohen CJ , RebolloR, BabovicS, DaiEL, RobinsonWP, MagerDL. Placenta-specific expression of the interleukin-2 (IL-2) receptor β subunit from an endogenous retroviral promoter. J. Biol. Chem.286(41) , 35543–35552 (2011).
   PubMed Web of Science ®Google Scholar
• Gimenez J , MontgiraudC, OriolGet al. Comparative methylation of ERVWE1/syncytin-1 and other human endogenous retrovirus LTRs in placenta tissues. DNA Res. 16(4) , 195–211 (2009).
   PubMed Web of Science ®Google Scholar
• Chuang HC , ChangCW, ChangGD, YaoTP, ChenH. Histone deacetylase 3 binds to and regulates the GCMα transcription factor. Nucleic Acids Res.34 , 1459–1469 (2006).
   PubMed Web of Science ®Google Scholar
• Weier JF , FerlatteC, WeierHU. Somatic genomic variations in extra-embryonic tissues. Curr. Genomics11(6) , 402–408 (2010).
   PubMed Web of Science ®Google Scholar
• Robinson WP , LauzonJL, InnesAM, LimK, ArsovskaS, McFaddenDE. Origin and outcome of pregnancies affected by androgenetic/biparental chimerism. Hum. Reprod.22 , 1114–1122 (2007).
   PubMed Web of Science ®Google Scholar
• Rosenberg MJ , WolffCR, El-EmawyA, StaplesMC, Perrone-BizzozeroNI, SavageDD. Effects of moderate drinking during pregnancy on placental gene expression. Alcohol44(7–8) , 673–690 (2010).
   PubMed Web of Science ®Google Scholar
• Votavova H , Dostalova Merkerova M, Fejglova K et al. Transcriptome alterations in maternal and fetal cells induced by tobacco smoke. Placenta32(10) , 763–770 (2011).
   PubMed Web of Science ®Google Scholar
• Marouani N , TebourbiO, MokniMet al. Embryotoxicity and fetotoxicity following intraperitoneal administrations of hexavalent chromium to pregnant rats. Zygote 19(3) , 229–235 (2011).
   PubMed Web of Science ®Google Scholar
• Eriksson JG . Early growth and coronary heart disease and type 2 diabetes: findings from the Helsinki Birth Cohort Study (HBCS). Am. J. Clin. Nutr.94(Suppl. 6) , S1799–S1802 (2011).
   PubMed Web of Science ®Google Scholar
• Gruslin A , LemyreB. Pre-eclampsia: fetal assessment and neonatal outcomes. Best Pract. Res. Clin. Obstet. Gynaecol.25(4) , 491–507 (2011).
   PubMed Web of Science ®Google Scholar
• Brosens I , PijnenborgR, VercruysseL, RomeroR. The “great obstetrical syndromes” are associated with disorders of deep placentation. Am. J. Obstet. Gynecol.204(3) , 193–201 (2011).
   PubMed Web of Science ®Google Scholar
• Senner CE , HembergerM. Regulation of early trophoblast differentiation – lessons from the mouse. Placenta31(11) , 944–950 (2010).
   PubMed Web of Science ®Google Scholar
• Szabova L , SonMY, ShiJet al. Membrane-type MMPs are indispensable for placental labyrinth formation and development. Blood 116(25) , 5752–5761 (2010).
   PubMed Web of Science ®Google Scholar
• Garcia-Gonzalez MA , OutedaP, ZhouQet al. Pkd1 and Pkd2 are required for normal placental development. PLoS ONE5(9) , e12821 (2010).
   PubMedGoogle Scholar
• Wu G , Imhoff-KunschB, GirardAW. Biological mechanisms for nutritional regulation of maternal health and fetal development. Paediatr. Perinat. Epidemiol.26(Suppl. 1) , S4–S26 (2012).
   PubMed Web of Science ®Google Scholar
• Aviram A , HodM, YogevY. Maternal obesity: implications for pregnancy outcome and long-term risks – a link to maternal nutrition. Int. J. Gynaecol. Obstet.115(Suppl. 1) , S6–S10 (2011).
   PubMed Web of Science ®Google Scholar
• Marshall NE , GuildC, ChengYW, CaugheyAB, HalloranDR. Maternal superobesity and perinatal outcomes. Am. J. Obstet. Gynecol.206(5) , 417 e1–e6 (2012).
   Google Scholar
• Gallou-Kabani C , GaboryA, TostJet al. Sex- and diet-specific changes of imprinted gene expression and DNA methylation in mouse placenta under a high-fat diet. PLoS ONE 21 , 5(12), e14398 (2010).
   Google Scholar
• Frias AE , MorganTK, EvansAEet al. Maternal high-fat diet disturbs uteroplacental hemodynamics and increases the frequency of stillbirth in a nonhuman primate model of excess nutrition. Endocrinology 152(6) , 2456–2464 (2011).
   PubMed Web of Science ®Google Scholar
• Hayes EK , LechowiczA, PetrikJJ. Adverse fetal and neonatal outcomes associated with a life-long high fat diet: role of altered development of the placental vasculature. PLoS ONE7(3) , e33370 (2012).
   PubMed Web of Science ®Google Scholar
• McMinn J , WeiM, SchupfNet al. Unbalanced placental expression of imprinted genes in human intrauterine growth restriction. Placenta 27(6–7) , 540–549 (2006).
   PubMed Web of Science ®Google Scholar
• Koukoura O , SifakisS, SouflaGet al. Loss of imprinting and aberrant methylation of IGF2 in placentas from pregnancies complicated with fetal growth restriction. Int. J. Mol. Med. 28(4) , 481–487 (2011).
   PubMed Web of Science ®Google Scholar
• Smith AC , ChoufaniS, FerreiraJC, WeksbergR. Growth regulation, imprinted genes, and chromosome 11p15.5. Pediatr. Res.61(5 Pt 2) , 43R–47R (2007).
   PubMed Web of Science ®Google Scholar
• Guo L , ChoufaniS, FerreiraJet al. Altered gene expression and methylation of the human chromosome 11 imprinted region in small for gestational age (SGA) placentae. Dev. Biol. 320(1) , 79–91 (2008).
   PubMed Web of Science ®Google Scholar
• Gao WL , LiD, XiaoZX. Detection of global DNA methylation and paternally imprinted H19 gene methylation in preeclamptic placentas. Hypertens. Res.34(5) , 655–661 (2011).
   PubMed Web of Science ®Google Scholar
• Diplas AI , LambertiniL, LeeMJet al. Differential expression of imprinted genes in normal and IUGR human placentas. Epigenetics 4(4) , 235–240 (2009).
   PubMed Web of Science ®Google Scholar
• Chmurzynska A . Fetal programming: link between early nutrition, DNA methylation, and complex diseases. Nutr. Rev.68(2) , 87–98 (2010).
   PubMed Web of Science ®Google Scholar
• Goyal R , GoyalD, LeitzkeA, GheorgheCP, LongoLD. Brain renin–angiotensin system: fetal epigenetic programming by maternal protein restriction during pregnancy. Reprod. Sci.17(3) , 227–238 (2010).
   PubMed Web of Science ®Google Scholar
• Kulkarni A , DangatK, KaleA, SableP, Chavan-GautamP, JoshiS. Effects of altered maternal folic acid, vitamin B12 and docosahexaenoic acid on placental global DNA methylation patterns in Wistar rats. PLoS ONE6(3) , e17706 (2011).
   PubMed Web of Science ®Google Scholar
• McKay JA , MathersJC. Diet induced epigenetic changes and their implications for health. Acta Physiol. (Oxf.)202(2) , 103–118 (2011).
   PubMed Web of Science ®Google Scholar
• Lillycrop KA , Slater-JefferiesJL, HansonMA, GodfreyKM, JacksonAA, BurdgeGC. Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyltransferase-1 expression is involved in impaired DNA methylation and changes in histone modifications. Br. J. Nutr.97 , 1064–1073 (2007).
   PubMed Web of Science ®Google Scholar
• Simpson JL , BaileyLB, PietrzikK, ShaneB, HolzgreveW. Micronutrients and women of reproductive potential: required dietary intake and consequences of dietary deficiency or excess. Part I–Folate, vitamin B12, vitamin B6. J. Matern. Fetal Neonatal Med.23(12) , 1323–1343 (2010).
   PubMed Web of Science ®Google Scholar
• Dasarathy J , GrucaLL, BennettCet al. Methionine metabolism in human pregnancy. Am. J. Clin. Nutr. 91(2) , 357–365 (2010).
   PubMed Web of Science ®Google Scholar
• Vacek TP , VacekJC, TyagiSC. Mitochondrial mitophagic mechanisms of myocardial matrix metabolism and remodelling. Arch. Physiol. Biochem.118(1) , 31–42 (2012).
   PubMed Web of Science ®Google Scholar
• Ke XD , Foucault-BertaudA, GenovesioC, Dignat-GeorgeF, LamyE, CharpiotP. Homocysteine modulates the proteolytic potential of human arterial smooth muscle cells through a reactive oxygen species dependant mechanism. Mol. Cell. Biochem.335(1–2) , 203–210 (2010).
   PubMed Web of Science ®Google Scholar
• Tong W , ZhangL. Fetal hypoxia and programming of matrix metalloproteinases. Drug Discov. Today17(3–4) , 124–134 (2012).
   PubMed Web of Science ®Google Scholar
• Pringle KG , KindKL, Sferruzzi-PerriAN, ThompsonJG, RobertsCT. Beyond oxygen, complex regulation and activity of hypoxia inducible factors in pregnancy. Hum. Reprod. Update16(4) , 415–431 (2010).
   PubMed Web of Science ®Google Scholar
• De Marco CS , CaniggiaI. Mechanisms of oxygen sensing in human trophoblast cells. Placenta23(Suppl. A) , S58–S68 (2002).
   PubMed Web of Science ®Google Scholar
• Rosario GX , KonnoT, SoaresMJ. Maternal hypoxia activates endovascular trophoblast cell invasion. Dev. Biol.314(2) , 362–375 (2008).
   PubMed Web of Science ®Google Scholar
• Tal R , ShaishA, BarshackIet al. Effects of hypoxia-inducible factor-1α overexpression in pregnant mice: possible implications for preeclampsia and intrauterine growth restriction. Am. J. Pathol. 177(6) , 2950–2962 (2010).
   PubMed Web of Science ®Google Scholar
• Roh CR , BudhrajaV, KimHS, NelsonDM, SadovskyY. Microarray-based identification of differentially expressed genes in hypoxic term human trophoblasts and in placental villi of pregnancies with growth restricted fetuses. Placenta26(4) , 319–328 (2005).
   PubMed Web of Science ®Google Scholar
• Nishizawa H , OtaS, SuzukiMet al. Comparative gene expression profiling of placentas from patients with severe pre-eclampsia and unexplained fetal growth restriction. Reprod. Biol. Endocrinol. 9 , 107 (2011).
   PubMed Web of Science ®Google Scholar
• Gascoin-Lachambre G , BuffatC, RebourcetRet al. Cullins in human intra-uterine growth restriction: expressional and epigenetic alterations. Placenta 31(2) , 151–157 (2010).
   PubMed Web of Science ®Google Scholar
• Fu J , LvX, LinHet al. Ubiquitin ligase cullin 7 induces epithelial-mesenchymal transition in human choriocarcinoma cells. J. Biol. Chem. 285(14) , 10870–10879 (2010).
   PubMed Web of Science ®Google Scholar
• Gheorghe CP , MohanS, ObergKC, LongoLD. Gene expression patterns in the hypoxic murine placenta: a role in epigenesis? Reprod. Sci.14(3) , 223–233 (2007).
   PubMed Web of Science ®Google Scholar
• Mouillet JF , ChuT, HubelCA, NelsonDM, ParksWT, SadovskyY. The levels of hypoxia-regulated microRNAs in plasma of pregnant women with fetal growth restriction. Placenta31(9) , 781–784 (2010).
   PubMed Web of Science ®Google Scholar
• Shruti K , ShreyK, VibhaR. Micro RNAs: tiny sequences with enormous potential. Biochem. Biophys. Res. Commun.407(3) , 445–449 (2011).
   PubMed Web of Science ®Google Scholar
• Pineles BL , RomeroR, MontenegroDet al. Distinct subsets of microRNAs are expressed differentially in the human placentas of patients with preeclampsia. Am. J. Obstet. Gynecol. 196(3) , 261. e1–e6 (2007).
   PubMed Web of Science ®Google Scholar
• Mayor-Lynn K , ToloubeydokhtiT, CruzAC, CheginiN. Expression profile of microRNAs and mRNAs in human placentas from pregnancies complicated by preeclampsia and preterm labor. Reprod. Sci. (1) , 46–56 (2011).
   PubMed Web of Science ®Google Scholar
• Kuehbacher A , UrbichC, ZeiherAM, DimmelerS. Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis. Circ. Res.101(1) , 59–68 (2007).
   PubMed Web of Science ®Google Scholar
• Yang WJ , YangDD, NaS, SanduskyGE, ZhangQ, ZhaoG. Dicer is required for embryonic angiogenesis during mouse development. J. Biol. Chem.280 , 9330–9335 (2005).
   PubMed Web of Science ®Google Scholar
• Kim KM , ParkSJ, JungSHet al. miR-182 is a negative regulator of osteoblast proliferation, differentiation, and skeletogenesis through targeting FoxO1. J. Bone Miner. Res. 27(8) , 1669–1679 (2012).
   PubMed Web of Science ®Google Scholar
• Contreras J , RaoDS. MicroRNAs in inflammation and immune responses. Leukemia26(3) , 404–413 (2012).
   PubMed Web of Science ®Google Scholar
• Warning JC , McCrackenSA, MorrisJM. A balancing act: mechanisms by which the fetus avoids rejection by the maternal immune system. Reproduction141(6) , 715–724 (2011).
   PubMed Web of Science ®Google Scholar
• Bernardi FC , FelisbertoF, VuoloFet al. Oxidative damage, inflammation, and toll-like receptor 4 pathway are increased in preeclamptic patients: a case–control study. Oxid. Med. Cell. Longev. 636419 (2012).
   PubMed Web of Science ®Google Scholar
• Bobetsis YA , BarrosSP, LinDMet al. Bacterial infection promotes DNA hypermethylation. J. Dent. Res. 86(2) , 169–174 (2007).
   PubMed Web of Science ®Google Scholar
• Suter M , AbramoviciA, Aagaard-TilleryK. Genetic and epigenetic influences associated with intrauterine growth restriction due to in utero tobacco exposure. Pediatr. Endocrinol. Rev.8(2) , 94–102 (2010).
   PubMedGoogle Scholar
• Maccani MA , Avissar-WhitingM, BanisterCE, McGonnigalB, PadburyJF, MarsitCJ. Maternal cigarette smoking during pregnancy is associated with downregulation of miR-16, miR-21, and miR-146a in the placenta. Epigenetics5(7) , 583–589 (2010).
   PubMed Web of Science ®Google Scholar
• Huuskonen P , StorvikM, ReinisaloMet al. Microarray analysis of the global alterations in the gene expression in the placentas from cigarette-smoking mothers. Clin. Pharmacol. Ther. 83 , 542–550 (2008).
   PubMed Web of Science ®Google Scholar
• Christensen BC , HousemanEA, MarsitCJet al. Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet. 5 , e1000602 (2009).
   PubMed Web of Science ®Google Scholar
• Shoemaker R , DengJ, WangW, ZhangK. Allele-specific methylation is prevalent and is contributed by CpG-SNPs in the human genome. Genome Res.20 , 883–889 (2010).
   PubMed Web of Science ®Google Scholar
• Yuen RK , AvilaL, PenaherreraMSet al. Human placental-specific epipolymorphism and its association with adverse pregnancy outcomes. PLoS ONE 4 , e7389 (2009).
   PubMed Web of Science ®Google Scholar
• Jimenez-Chillaron JC , IsganaitisE, CharalambousMet al. Intergenerational transmission of glucose intolerance and obesity by in utero undernutrition in mice. Diabetes 58 , 460–468 (2009).
   PubMed Web of Science ®Google Scholar
• Barker DJ . Developmental origins of adult health and disease. J. Epidemiol. Community Health58 , 114 –115 (2004).
   PubMed Web of Science ®Google Scholar
• Jin W , PattiME. Genetic determinants and molecular pathways in the pathogenesis of Type 2 diabetes. Clin. Sci.116 , 99–111 (2009).
   Web of Science ®Google Scholar
• Yajnik CS , DeshpandeSS, JacksonAAet al. Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study. Diabetologia 51(1) , 29–38 (2008).
   PubMed Web of Science ®Google Scholar
• Ravelli AC , van Der Meulen JH, Osmond C, Barker DJ, Bleker OP. Obesity at the age of 50 y in men and women exposed to famine prenatally. Am. J. Clin. Nutr.70(5) , 811–816 (1999).
   PubMed Web of Science ®Google Scholar
• Barker DJ , GelowJ, ThornburgK, OsmondC, KajantieE, ErikssonJG. The early origins of chronic heart failure: impaired placental growth and initiation of insulin resistance in childhood. Eur. J. Heart Fail.12(8) , 819–825 (2010).
   PubMed Web of Science ®Google Scholar
• Laughon M , BoseC, AllredENet al. Antecedents of chronic lung disease following three patterns of early respiratory disease in preterm infants. Arch. Dis. Child Fetal Neonatal Ed. 96(2) , F114–F120 (2011).
   PubMed Web of Science ®Google Scholar
• Karadag A , SakuraiR, WangYet al. Effect of maternal food restriction on fetal rat lung lipid differentiation program. Pediatr. Pulmonol. 44(7) , 635–644 (2009).
   PubMed Web of Science ®Google Scholar
• Rexhaj E , BlochJ, JayetPYet al. Fetal programming of pulmonary vascular dysfunction in mice: role of epigenetic mechanisms. Am. J. Physiol. Heart Circ. Physiol. 301(1) , H247–H252 (2011).
   PubMed Web of Science ®Google Scholar
• Susser E , HoekHW, BrownA. Neurodevelopmental disorders after prenatal famine: the story of the Dutch Famine Study. Am. J. Epidemiol.147 , 213–216 (1998).
   PubMed Web of Science ®Google Scholar
• St Clair D , XuM, WangPet al. Rates of adult schizophrenia following prenatal exposure to the Chinese famine of 1959–1961. JAMA 294 , 557–562 (2005).
   PubMed Web of Science ®Google Scholar
• Ke X , LeiQ, JamesSJet al. Uteroplacental insufficiency affects epigenetic determinants of chromatin structure in brains of neonatal and juvenile IUGR rats. Physiol. Genomics 25 , 16–28 (2006).
   PubMed Web of Science ®Google Scholar
• Jensen Peña C , MonkC, ChampagneFA. Epigenetic effects of prenatal stress on 11β-hydroxysteroid dehydrogenase-2 in the placenta and fetal brain. PLoS ONE7(6) , e39791 (2012).
   PubMed Web of Science ®Google Scholar
• Wyrwoll CS , HolmesMC. Prenatal excess glucocorticoid exposure and adult affective disorders: a role for serotonergic and catecholamine pathways. Neuroendocrinology95(1) , 47–55 (2012).
   PubMed Web of Science ®Google Scholar
• Vucetic Z , TotokiK, SchochHet al. Early life protein restriction alters dopamine circuitry. Neuroscience 168(2) , 359–370 (2010).
   PubMed Web of Science ®Google Scholar
• Ramachandran A , SnehalathaC, ShettyAS, NandithaA. Trends in prevalence of diabetes in Asian countries. World J. Diabetes3(6) , 110–117 (2012).
   PubMedGoogle Scholar
• Maclean PS , BergouignanA, CornierMA, JackmanMR. Biology‘s response to dieting: the impetus for weight regain. Am. J. Physiol. Regul. Integr. Comp. Physiol.301(3) R581–R600 (2011).
   PubMed Web of Science ®Google Scholar
• Stoffers DA , DesaiBM, DeLeonDD, SimmonsRA. Neonatal exendin-4 prevents the development of diabetes in the intrauterine growth retarded rat. Diabetes52 , 734–740 (2003).
   PubMed Web of Science ®Google Scholar
• Lambertini L , DiplasAI, LeeMJ, SperlingR, ChenJ, WetmurJ. A sensitive functional assay reveals frequent loss of genomic imprinting in human placenta. Epigenetics3 , 261–269 (2008).
   PubMed Web of Science ®Google Scholar
• Yuen RK , PenaherreraMS, von Dadelszen P, McFadden DE, Robinson WP. DNA methylation profiling of human placentae reveals promoter hypomethylation of multiple genes in early-onset preeclampsia. Eur. J. Hum. Genet.18 , 1006–1012 (2010).
   PubMed Web of Science ®Google Scholar
• Lo YM , CorbettaN, ChamberlainPFet al. Presence of fetal DNA in maternal plasma and serum. Lancet 350(9076) , 485–487 (1997).
   PubMed Web of Science ®Google Scholar
• Illanes S , ParraM, SerraRet al. Increased free fetal DNA levels in early pregnancy plasma of women who subsequently develop preeclampsia and intrauterine growth restriction. Prenat. Diagn. 29(12) , 1118–1122 (2009).
   PubMed Web of Science ®Google Scholar
• Sifakis S , ZaravinosA, MaizN, SpandidosDA, NicolaidesKH. First-trimester maternal plasma cell-free fetal DNA and preeclampsia. Am. J. Obstet. Gynecol.201(5) , 472.e1–e7 (2009).
   PubMed Web of Science ®Google Scholar
• Papageorgiou EA , KaragrigoriouA, TsalikiE, VelissariouV, CarterNP, PatsalisPC. Fetal-specific DNA methylation ratio permits noninvasive prenatal diagnosis of trisomy 21. Nat. Med.17(4) , 510–513 (2011).
   PubMed Web of Science ®Google Scholar
• Adamo KB , FerraroZM, BrettKE. Can we modify the intrauterine environment to halt the intergenerational cycle of obesity? Int. J. Environ. Res. Public Health9(4) , 1263–1307 (2012).
   PubMed Web of Science ®Google Scholar

▪ Website

• WHO: Obesity and Overweight, Fact Sheet No. 311 (2012). www.who.int/mediacentre/factsheets/fs311/en
   Google Scholar