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EPIGENETIC PROGRAMMING AND FETAL GROWTH RESTRICTIONS

Part of: Bespoke shallow archive Weizmann

Published online by Cambridge University Press:  03 June 2010

JOSE CARLOS FERREIRA ,
SANAA CHOUFANI ,
JOHN KINGDOM  and
ROSANNA WEKSBERG
JOSE CARLOS FERREIRA
Affiliation:
Program in Genetics and Genome Biology, Hospital for Sick Children Research Institute, Toronto, ON, Canada University of Toronto, Toronto, ON, Canada
SANAA CHOUFANI
Affiliation:
Program in Genetics and Genome Biology, Hospital for Sick Children Research Institute, Toronto, ON, Canada
JOHN KINGDOM
Affiliation:
Maternal–Fetal Medicine Division, Department of Obstetrics and Gynecology, Mount Sinai Hospital, Toronto, ON, Canada University of Toronto, Toronto, ON, Canada
ROSANNA WEKSBERG*
Affiliation:
Program in Genetics and Genome Biology, Hospital for Sick Children Research Institute, Toronto, ON, Canada Division of Clinical and Metabolic Genetics, Hospital for Sick Children, Toronto, ON, Canada University of Toronto, Toronto, ON, Canada
*
Rosanna Weksberg, Hospital for Sick Children, Division of Clinical and Metabolic Genetics, 525 University Avenue, Suite 940, 9th Floor, Toronto, Ontario M5G 1X8Canada. Email address: rweksb@sickkids.ca
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Extract

Normal fetal growth and development depends on multiple molecular mechanisms that coordinate both placental and fetal development. Efforts to better understand fetal/placental growth dysregulation and fetal growth restriction (FGR) are now being driven by several findings that highlight the longterm impact of FGR on susceptibility to disease. The association of poor fetal growth to perinatal medical complications is well accepted but more recent data also show that FGR is linked to common, serious adult health problems. Several large-scale human epidemiological studies from diverse countries have shown that conditions such as coronary heart disease, hypertension, stroke, type 2 diabetes mellitus, adiposity, insulin resistance and osteoporosis are more prevalent in individuals with a history of low birthweight.

Type
Research Article
Information
Fetal and Maternal Medicine Review , Volume 21 , Issue 3 , August 2010 , pp. 204 - 224
Copyright
Copyright © Cambridge University Press 2010

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References

REFERENCES

1Barker, DJ, Winter, PD, Osmond, C, Margetts, B, Simmonds, SJ. Weight in infancy and death from ischaemic heart disease. Lancet. 1989; 2ii: 577–80.CrossRefGoogle Scholar
2Osmond, C, Barker, DJ, Winter, PD, Fall, CH, Simmonds, SJ. Early growth and death from cardiovascular disease in women. Br Med J 1993; 307: 1519–24.Google Scholar
3Hales, CN, Barker, DJ, Clark, PM, , Cox LJ, Fall, C, Osmond, C, et al. Fetal and infant growth and impaired glucose tolerance at age 64. Br Med J 1991; 303: 1019–22.CrossRefGoogle ScholarPubMed
4Leon, DA, Lithell, HO, Vagero, D, Koupilova, I, Mohsen, R, Berglund, L, et al. Reduced fetal growth rate and increased risk of death from ischaemic heart disease: cohort study of 15 000 Swedish men and women born 1915–29. Br Med J 1998; 317: 241–45.Google Scholar
5Lithell, HO, McKeigue, PM, Berglund, L, Mohsen, R, Lithell, UB, Leon, DA. Relation of size at birth to non-insulin dependent diabetes and insulin concentrations in men aged 50–60 years. Br Med J 1996; 312: 406–10.CrossRefGoogle ScholarPubMed
6Forsen, T, Eriksson, J, Tuomilehto, J, Reunanen, A, Osmond, C, Barker, D. The fetal and childhood growth of persons who develop type 2 diabetes. Ann Intern Med 2000; 133: 176–82.CrossRefGoogle ScholarPubMed
7Barker, DJ, Hales, CN, Fall, CH, Osmond, C, Phipps, K, Clark, PM. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 1993; 36: 62–67.CrossRefGoogle ScholarPubMed
8Dennison, EM, Syddall, HE, Sayer, AA, Gilbody, HJ, Cooper, C. Birth weight and weight at 1 year are independent determinants of bone mass in the seventh decade: the Hertfordshire cohort study. Pediatr Res 2005; 57: 582–86.Google Scholar
9Antoniades, L, MacGregor, AJ, Andrew, T, Spector, TD. Association of birth weight with osteoporosis and osteoarthritis in adult twins. Rheumatology 2003; 42: 791–96.CrossRefGoogle ScholarPubMed
10Yarbrough, DE, Barrett-Connor, E, Morton, DJ. Birth weight as a predictor of adult bone mass in postmenopausal women: the Rancho Bernardo Study. Osteoporos Int 2000; 11: 626–30.Google Scholar
11Godfrey, KM, Barker, DJ. Fetal nutrition and adult disease. Am J Clin Nutr 2000; 71: 1344S–52S.Google Scholar
12Roseboom, TJ, Van Der Meulen, JH, Ravelli, AC, Osmond, C, Barker, DJ, Bleker, OP. Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview. Twin Res 2001; 4: 293–98.CrossRefGoogle Scholar
13Chaddha, V, Viero, S, Huppertz, B, Kingdom, J. Developmental biology of the placenta and the origins of placental insufficiency. Semin Fetal Neonatal Med 2004; 9: 357–69.Google Scholar
14Coleman, MA, McCowan, LM, North, RA. Mid-trimester uterine artery Doppler screening as a predictor of adverse pregnancy outcome in high-risk women. Ultrasound Obstet Gynecol 2000; 15: 7–12.Google Scholar
15Ghosh, G, Breborowicz, A, Brazert, M, Maczkiewicz, M, Kobelski, M, Dubiel, M, et al. Evaluation of third trimester uterine artery flow velocity indices in relationship to perinatal complications. J Matern Fetal Neonatal Med 2006; 19: 551–55.Google Scholar
16Cnossen, JS, Morris, RK, ter Riet, G, Mol, BW, Van Der Post, JA, Coomarasamy, A, et al. Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis. CMAJ. 2008; 178: 701–11.Google Scholar
17Todros, T, Sciarrone, A, Piccoli, E, Guiot, C, Kaufmann, P, Kingdom, J. Umbilical Doppler waveforms and placental villous angiogenesis in pregnancies complicated by fetal growth restriction. Obstet Gynecol 1999; 93: 499–503.Google Scholar
18Kingdom, J, Huppertz, B, Seaward, G, Kaufmann, P. Development of the placental villous tree and its consequences for fetal growth. Eur J Obstet Gynecol Reprod Biol 2000; 92: 35–43.CrossRefGoogle ScholarPubMed
19Baschat, AA, Gembruch, U, Reiss, I, Gortner, L, Weiner, CP, Harman, CR. Relationship between arterial and venous Doppler and perinatal outcome in fetal growth restriction. Ultrasound Obstet Gynecol 2000; 16: 407–13.CrossRefGoogle ScholarPubMed
20Redline, RW, Heller, D, Keating, S, Kingdom, J. Placental diagnostic criteria and clinical correlation–a workshop report. Placenta 2005; 26 Suppl A: S114–17.CrossRefGoogle ScholarPubMed
21Mayhew, TM, Manwani, R, Ohadike, C, Wijesekara, J, Baker, PN. The placenta in pre-eclampsia and intrauterine growth restriction: studies on exchange surface areas, diffusion distances and villous membrane diffusive conductances. Placenta 2007; 28: 233–38.Google Scholar
22Kadyrov, M, Kingdom, JC, Huppertz, B. Divergent trophoblast invasion and apoptosis in placental bed spiral arteries from pregnancies complicated by maternal anemia and early-onset preeclampsia/intrauterine growth restriction. Am J Obstet Gynecol 2006; 194: 557–63.Google Scholar
23Madazli, R, Somunkiran, A, Calay, Z, Ilvan, S, Aksu, MF. Histomorphology of the placenta and the placental bed of growth restricted foetuses and correlation with the Doppler velocimetries of the uterine and umbilical arteries. Placenta 2003; 24: 510–16.Google Scholar
24Maulik, D. Management of fetal growth restriction: an evidence-based approach. Clin Obstet Gynecol 2006; 49: 320–34.Google Scholar
25Pallotto, EK, Kilbride, HW. Perinatal outcome and later implications of intrauterine growth restriction. Clin Obstet Gynecol 2006; 49: 257–69.Google Scholar
26Selling, KE, Carstensen, J, Finnstrom, O, Sydsjo, G. Intergenerational effects of preterm birth and reduced intrauterine growth: a population-based study of Swedish mother-offspring pairs. BJOG 2006; 113: 430–40.CrossRefGoogle ScholarPubMed
27Maulik, D. Fetal growth restriction: the etiology. Clin Obstet Gynecol 2006; 49: 228–35.Google Scholar
28Plouin, PF, Breart, G, Rabarison, Y, Rumeau-Rouquette, C, Sureau, C, Menard, J. Fetal growth retardation in gestational hypertension: relationships with blood pressure levels and the time of onset of hypertension. Eur J Obstet Gynecol Reprod Biol 1983; 16: 253–62.Google Scholar
29Sibai, BM. Chronic hypertension in pregnancy. Obstet Gynecol 2002; 100: 369–77.Google Scholar
30Helmerhorst, FM, Perquin, DA, Donker, D, Keirse, MJ. Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies. Br Med J 2004; 328: 261.Google Scholar
31Jackson, RA, Gibson, KA, Wu, YW, Croughan, MS. Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis. Obstet Gynecol 2004; 103: 551–63.Google Scholar
32McDonald, SD, Murphy, K, Beyene, J, Ohlsson, A. Perinatal outcomes of singleton pregnancies achieved by in vitro fertilization: a systematic review and meta-analysis. J Obstet Gynaecol Can 2005; 27: 449–59.Google Scholar
33Henriksen, T, Clausen, T. The fetal origins hypothesis: placental insufficiency and inheritance versus maternal malnutrition in well-nourished populations. Acta Obstet Gynecol Scand 2002; 81: 112–14.Google Scholar
34Pijnenborg, R. Uterine haemodynamics as a possible driving force for endovascular trophoblast migration in the placental bed. Med Hypotheses 2000; 55: 114–18.Google Scholar
35Meekins, JW, Pijnenborg, R, Hanssens, M, McFadyen, IR, van Asshe, A. A study of placental bed spiral arteries and trophoblast invasion in normal and severe pre-eclamptic pregnancies. Br J Obstet Gynaecol 1994; 101: 669–74.Google Scholar
36Biswas, S, Ghosh, SK, Chhabra, S. Surface area of chorionic villi of placentas: an index of intrauterine growth restriction of fetuses. J Obstet Gynaecol Res 2008; 34: 487–93.Google Scholar
37Redline, RW, Boyd, T, Campbell, V, Hyde, S, Kaplan, C, Khong, TY, et al. Maternal vascular underperfusion: nosology and reproducibility of placental reaction patterns. Pediatr Dev Pathol 2004; 7: 237–49.Google Scholar
38Toal, M, Chan, C, Fallah, S, Alkazaleh, F, Chaddha, V, Windrim, RC, et al. Usefulness of a placental profile in high-risk pregnancies. Am J Obstet Gynecol 2007; 196: 363 e1–7.Google Scholar
39Figueroa, R, Maulik, D. Prenatal therapy for fetal growth restriction. Clin Obstet Gynecol 2006; 49: 308–19.Google Scholar
40Mayhew, TM, Desoye, G. A simple method for comparing immunogold distributions in two or more experimental groups illustrated using GLUT1 labelling of isolated trophoblast cells. Placenta 2004; 25: 580–84.CrossRefGoogle ScholarPubMed
41Carter, AM, Hills, F, O'Gorman, DB, Roberts, CT, Sooranna, SR, Watson, CS, et al. The insulin-like growth factor system in mammalian pregnancy–a workshop report. Placenta 2004; 25 Suppl A: S53–6.CrossRefGoogle ScholarPubMed
42Joss-Moore, LA, Lane, RH. The developmental origins of adult disease. Curr Opin Pediatr 2009; 21: 230–34.Google Scholar
43Feinberg, AP. Phenotypic plasticity and the epigenetics of human disease. Nature 2007; 447: 433–40.CrossRefGoogle ScholarPubMed
44Edwards, CA, Ferguson-Smith, AC. Mechanisms regulating imprinted genes in clusters. Curr Opin Cell Biol 2007; 19: 281–89.Google Scholar
45Kacem, S, Feil, R. Chromatin mechanisms in genomic imprinting. Mamm Genome 2009; 20: 544–56.Google Scholar
46Recillas-Targa, F. DNA methylation, chromatin boundaries, and mechanisms of genomic imprinting. Arch Med Res 2002; 33: 428–38.CrossRefGoogle ScholarPubMed
47Valley, CM, Willard, HF. Genomic and epigenomic approaches to the study of X chromosome inactivation. Curr Opin Genet Dev 2006; 16: 240–45.Google Scholar
48Whitelaw, E, Martin, DI. Retrotransposons as epigenetic mediators of phenotypic variation in mammals. Nat Genet 2001; 27: 361–65.CrossRefGoogle ScholarPubMed
49Emerman, M, Temin, HM. Genes with promoters in retrovirus vectors can be independently suppressed by an epigenetic mechanism. Cell 1984; 39: 449–67.Google Scholar
50Reiss, D, Zhang, Y, Rouhi, A, Reuter, M, Mager, DL. Variable DNA methylation of transposable elements: The case study of mouse Early Transposons. Epigenetics 2010; 5: 68–79. Epub 2010 Jan 13.Google Scholar
51Mathers, JC. Early nutrition: impact on epigenetics. Forum Nutr 2007; 60: 42–48.CrossRefGoogle ScholarPubMed
52Heijmans, BT, Tobi, EW, Stein, AD, Putter, H, Blauw, GJ, Susser, ES, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A. 2008; 105: 17046–49.Google Scholar
53Chawla, RK, Watson, WH, Jones, DP. Effect of hypoxia on hepatic DNA methylation and tRNA methyltransferase in rat: similarities to effects of methyl-deficient diets. J Cell Biochem. 1996; 61: 72–80.Google Scholar
54Wellmann, S, Bettkober, M, Zelmer, A, Seeger, K, Faigle, M, Eltzschig, HK, et al. Hypoxia upregulates the histone demethylase JMJD1A via HIF-1. Biochem Biophys Res Commun 2008 372: 892–97.Google Scholar
55Yang, J, Ledaki, I, Turley, H, Gatter, KC, Montero, JC, Li, JL, et al. Role of hypoxia-inducible factors in epigenetic regulation via histone demethylases. Ann N Y Acad Sci 2009; 177: 185–97.Google Scholar
56Bird, A. DNA methylation patterns and epigenetic memory. Genes Dev 2002; 16: 6–21.Google Scholar
57Bogdanovic, O, Veenstra, GJ. DNA methylation and methyl-CpG binding proteins: developmental requirements and function. Chromosoma. 2009; 118: 549–65.Google Scholar
58Suzuki, MM, Bird, A. DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet 2008; 9: 465–76.Google Scholar
59Munshi, A, Shafi, G, Aliya, N, Jyothy, A. Histone modifications dictate specific biological readouts. J Genet Genomics 2009; 36: 75–88.Google Scholar
60Esteller, M. Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet 2007; 8: 286–98.CrossRefGoogle ScholarPubMed
61Kondo, Y, Shen, L, Cheng, AS, Ahmed, S, Boumber, Y, Charo, C, et al. Gene silencing in cancer by histone H3 lysine 27 trimethylation independent of promoter DNA methylation. Nat Genet 2008; 40: 741–50.CrossRefGoogle ScholarPubMed
62Kondo, Y, Shen, L, Yan, PS, Huang, TH, Issa, JP. Chromatin immunoprecipitation microarrays for identification of genes silenced by histone H3 lysine 9 methylation. Proc Natl Acad Sci U S A. 2004; 101: 7398–403.Google Scholar
63Stefani, G, Slack, FJ. Small non-coding RNAs in animal development. Nat Rev Mol Cell Biol 2008; 9: 219–30.Google Scholar
64Chuang, JC, Jones, PA. Epigenetics and microRNAs. Pediatr Res 2007; 61: 24R–9R.Google Scholar
65Pavri, R, Lewis, B, Kim, TK, Dilworth, FJ, Erdjument-Bromage, H, Tempst, P, et al. PARP-1 determines specificity in a retinoid signaling pathway via direct modulation of mediator. Mol Cell 2005; 18: 83–96.CrossRefGoogle Scholar
66Marsit, CJ, Eddy, K, Kelsey, KT. MicroRNA responses to cellular stress. Cancer Res 2006; 66: 10843–848.CrossRefGoogle ScholarPubMed
67Griffiths-Jones, S, Saini, HK, van Dongen, S, Enright, AJ. miRBase: tools for microRNA genomics. Nucleic Acids Res 2008; 36: D154–58.Google Scholar
68Royo, H, Cavaille, J. Non-coding RNAs in imprinted gene clusters. Biol Cell 2008; 100: 149–66.Google Scholar
69Morison, IM, Ramsay, JP, Spencer, HG. A census of mammalian imprinting. Trends Genet 2005; 21: 457–65. Updated at http://igc.otago.ac.nz/Summary-table.pdfGoogle Scholar
70Luedi, PP, Dietrich, FS, Weidman, JR, Bosko, JM, Jirtle, RL, Hartemink, AJ. Computational and experimental identification of novel human imprinted genes. Genome Res 2007; 17: 1723–30.Google Scholar
71Buiting, K, Saitoh, S, Gross, S, Dittrich, B, Schwartz, S, Nicholls, RD, et al. Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting centre on human chromosome 15. Nat Genet 1995; 9: 395–400.Google Scholar
72Horsthemke, B, Buiting, K. Genomic imprinting and imprinting defects in humans. Adv Genet 2008; 61: 225–46.Google Scholar
73Constancia, M, Pickard, B, Kelsey, G, Reik, W. Imprinting mechanisms. Genome Res 1998; 8: 881–900.Google Scholar
74Arnaud, P, Feil, R. Epigenetic deregulation of genomic imprinting in human disorders and following assisted reproduction. Birth Defects Res C Embryo Today. 2005; 75: 81–97.CrossRefGoogle ScholarPubMed
75Reik, W, Constancia, M, Fowden, A, Anderson, N, Dean, W, Ferguson-Smith, A, et al. Regulation of supply and demand for maternal nutrients in mammals by imprinted genes. J Physiol 2003; 547: 35–44.CrossRefGoogle ScholarPubMed
76Tycko, B, Morison, IM. Physiological functions of imprinted genes. J Cell Physiol 2002; 192: 245–58.Google Scholar
77Eich, GF, Silver, MM, Weksberg, R, Daneman, A, Costa, T. Marshall-Smith syndrome: new radiographic, clinical, and pathologic observations. Radiology 1991; 181: 183–88.CrossRefGoogle ScholarPubMed
78Moore, T, Haig, D. Genomic imprinting in mammalian development: a parental tug-of-war. Trends Genet 1991; 7: 45–49.Google Scholar
79Varmuza, S, Mann, M. Genomic imprinting–defusing the ovarian time bomb. Trends Genet 1994; 10: 118–23.Google Scholar
80Weksberg, R, Shuman, C, Smith, AC. Beckwith-Wiedemann syndrome. Am J Med Genet C Semin Med Genet. 2005; 137C: 12–23.Google Scholar
81Squire, JA, Li, M, Perlikowski, S, Fei, YL, Bayani, J, Zhang, ZM, et al. Alterations of H19 imprinting and IGF2 replication timing are infrequent in Beckwith-Wiedemann syndrome. Genomics 2000; 65: 234–42.Google Scholar
82Weksberg, R, Shen, DR, Fei, YL, Song, QL, Squire, J. Disruption of insulin-like growth factor 2 imprinting in Beckwith-Wiedemann syndrome. Nat Genet 1993; 5: 143–50.Google Scholar
83Gicquel, C, Rossignol, S, Cabrol, S, Houang, M, Steunou, V, Barbu, V, et al. Epimutation of the telomeric imprinting center region on chromosome 11p15 in Silver-Russell syndrome. Nat Genet 2005; 37: 1003–1007.Google Scholar
84Horike, S, Ferreira, JC, Meguro-Horike, M, Choufani, S, Smith, AC, Shuman, C, et al. Screening of DNA methylation at the H19 promoter or the distal region of its ICR1 ensures efficient detection of chromosome 11p15 epimutations in Russell-Silver syndrome. Am J Med Genet A 2009; 149A: 2415–423.Google Scholar
85Abu-Amero, S, Monk, D, Frost, J, Preece, M, Stanier, P, Moore, GE. The genetic aetiology of Silver-Russell syndrome. J Med Genet 2008; 45: 193–99.Google Scholar
86Martin-Subero, JI, Bibikova, M, Mackay, D, Wickham-Garcia, E, Sellami, N, Richter, J, et al. Microarray-based DNA methylation analysis of imprinted loci in a patient with transient neonatal diabetes mellitus. Am J Med Genet A 2008; 146A: 3227–29.Google Scholar
87Sharma, S, Kelly, TK, Jones, PA. Epigenetics in cancer. Carcinogenesis. 2010; 31: 27–36. Epub 2009 Sep 13.Google Scholar
88Duvic, M, Vu, J. Vorinostat in cutaneous T-cell lymphoma. Drugs Today (Barc). 2007; 43: 585–99.Google Scholar
89Szyf, M. Epigenetics, DNA methylation, and chromatin modifying drugs. Annu Rev Pharmacol Toxicol 2009; 49: 243–63.Google Scholar
90Park, BH, Kim, YJ, Park, JS, Lee, HY, Ha, EH, Min, JW, et al. [Folate and homocysteine levels during pregnancy affect DNA methylation in human placenta]. J Prev Med Public Health 2005; 38: 437–42.Google Scholar
91Sharp, L, Little, J. Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review. Am J Epidemiol 2004; 159: 423–43.CrossRefGoogle ScholarPubMed
92Lissowska, J, Gaudet, MM, Brinton, LA, Chanock, SJ, Peplonska, B, Welch, R, et al. Genetic polymorphisms in the one-carbon metabolism pathway and breast cancer risk: a population-based case-control study and meta-analyses. Int J Cancer 2007; 120: 2696–703.Google Scholar
93Zogel, C, Bohringer, S, Gross, S, Varon, R, Buiting, K, Horsthemke, B. Identification of cis- and trans-acting factors possibly modifying the risk of epimutations on chromosome 15. Eur J Hum Genet 2006; 14: 752–58.Google Scholar
94Gilbody, S, Lewis, S, Lightfoot, T. Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HuGE review. Am J Epidemiol 2007; 165: 1–13.Google Scholar
95Mohammad, NS, Jain, JM, Chintakindi, KP, Singh, RP, Naik, U, Akella, RR. Aberrations in folate metabolic pathway and altered susceptibility to autism. Psychiatr Genet 2009; 19: 171–76.Google Scholar
96Collin, SM, Metcalfe, C, Zuccolo, L, Lewis, SJ, Chen, L, Cox, A, et al. Association of folate-pathway gene polymorphisms with the risk of prostate cancer: a population-based nested case-control study, systematic review, and meta-analysis. Cancer Epidemiol Biomarkers Prev 2009; 18: 2528–539.Google Scholar
97Wen, SW, Zhou, J, Yang, Q, Fraser, W, Olatunbosun, O, Walker, M. Maternal exposure to folic acid antagonists and placenta-mediated adverse pregnancy outcomes. CMAJ 2008; 179: 1263–268.Google Scholar
98Keating, E, Goncalves, P, Costa, F, Campos, I, Pinho, MJ, Azevedo, I, et al. Comparison of the transport characteristics of bioactive substances in IUGR and normal placentas. Pediatr Res 2009; 66: 495–500.Google Scholar
99Bossenmeyer-Pourie, C, Blaise, S, Pourie, G, Tomasetto, C, Audonnet, S, Ortiou, S, et al. Methyl donor deficiency affects fetal programming of gastric ghrelin cell organization and function in the rat. Am J Pathol 2010; 176: 270–77. Epub 2009 Nov 30.Google Scholar
100Kojima, M, Kangawa, K. Ghrelin: structure and function. Physiol Rev 2005; 85: 495–522.Google Scholar
101Torsello, A, Scibona, B, Leo, G, Bresciani, E, Avallone, R, Bulgarelli, I, et al. Ontogeny and tissue-specific regulation of ghrelin mRNA expression suggest that ghrelin is primarily involved in the control of extraendocrine functions in the rat. Neuroendocrinology 2003; 77: 91–99.Google Scholar
102Minard, ME, Jain, AK, Barton, MC. Analysis of epigenetic alterations to chromatin during development. Genesis 2009; 47: 559–72.Google Scholar
103Rakyan, VK, Down, TA, Thorne, NP, Flicek, P, Kulesha, E, Graf, S, et al. An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs). Genome Res 2008; 18: 1518–529.Google Scholar
104Romanov, GA, Vaniushin, BF. [Intragenomic specificity of DNA methylation in animals. Qualitative differences in tissues and changes in methylation of repeating sequences during aging, carcinogenesis and hormonal induction]. Mol Biol (Mosk). 1980; 14: 357–68.Google Scholar
105Wilson, VL, Smith, RA, Ma, S, Cutler, RG. Genomic 5-methyldeoxycytidine decreases with age. J Biol Chem 1987; 262: 9948–951.Google Scholar
106Maccani, MA, Marsit, CJ. Epigenetics in the placenta. Am J Reprod Immunol 2009; 62: 78–89.CrossRefGoogle ScholarPubMed
107Lewis, A, Mitsuya, K, Umlauf, D, Smith, P, Dean, W, Walter, J, et al. Imprinting on distal chromosome 7 in the placenta involves repressive histone methylation independent of DNA methylation. Nat Genet 2004; 36: 1291–95.Google Scholar
108Novakovic, B, Rakyan, V, Ng, HK, Manuelpillai, U, Dewi, C, Wong, NC, et al. Specific tumour-associated methylation in normal human term placenta and first-trimester cytotrophoblasts. Mol Hum Reprod 2008; 14: 547–54.Google Scholar
109Chiu, RW, Chim, SS, Wong, IH, Wong, CS, Lee, WS, To, KF, et al. Hypermethylation of RASSF1A in human and rhesus placentas. Am J Pathol 2007; 170: 941–50.Google Scholar
110Wong, NC, Novakovic, B, Weinrich, B, Dewi, C, Andronikos, R, Sibson, M, et al. Methylation of the adenomatous polyposis coli (APC) gene in human placenta and hypermethylation in choriocarcinoma cells. Cancer Lett 2008 8; 268: 56–62.Google Scholar
111Dokras, A, Coffin, J, Field, L, Frakes, A, Lee, H, Madan, A, et al. Epigenetic regulation of maspin expression in the human placenta. Mol Hum Reprod 2006; 12: 611–17.CrossRefGoogle ScholarPubMed
112Novakovic, B, Sibson, M, Ng, HK, Manuelpillai, U, Rakyan, VK, Down, TA, et al. Placenta specific methylation of the vitamin D 24-hydroxylase gene:Implications for feedback autoregulation of active vitamin D levels at the fetomaternal interface. J Biol Chem 2009; 284: 14838–848.Google Scholar
113Guo, L, Choufani, S, Ferreira, J, Smith, A, Chitayat, D, Shuman, C, et al. Altered gene expression and methylation of the human chromosome 11 imprinted region in small for gestational age (SGA) placentae. Dev Biol 2008; 320: 79–91.Google Scholar
114Jinno, Y, Ikeda, Y, Yun, K, Maw, M, Masuzaki, H, Fukuda, H, et al. Establishment of functional imprinting of the H19 gene in human developing placentae. Nature Genetics 1995; 10: 318–24.Google Scholar
115Donker, RB, Mouillet, JF, Nelson, DM, Sadovsky, Y. The expression of Argonaute2 and related microRNA biogenesis proteins in normal and hypoxic trophoblasts. Mol Hum Reprod 2007; 13: 273–79.Google Scholar
116Luo, SS, Ishibashi, O, Ishikawa, G, Ishikawa, T, Katayama, A, Mishima, T, et al. Human villous trophoblasts express and secrete placenta-specific microRNAs into maternal circulation via exosomes. Biol Reprod 2009; 81: 717–29.Google Scholar
117Deveault, C, Qian, JH, Chebaro, W, Ao, A, Gilbert, L, Mehio, A, et al. NLRP7 mutations in women with diploid androgenetic and triploid moles: a proposed mechanism for mole formation. Hum Mol Genet 2009; 18: 888–97.Google Scholar
118Liang, Y, Ridzon, D, Wong, L, Chen, C. Characterization of microRNA expression profiles in normal human tissues. BMC Genomics 2007; 8: 166.Google Scholar
119Ozanne, SE, Constancia, M. Mechanisms of disease: the developmental origins of disease and the role of the epigenotype. Nat Clin Pract Endocrinol Metab 2007; 3: 539–46.Google Scholar
120Reik, W, Dean, W, Walter, J. Epigenetic reprogramming in mammalian development. Science 2001; 293: 1089–93.Google Scholar
121Ferguson-Smith, AC, Surani, MA. Imprinting and the epigenetic asymmetry between parental genomes. Science 2001; 293: 1086–89.Google Scholar
122Sleutels, F, Zwart, R, Barlow, DP. The non-coding Air RNA is required for silencing autosomal imprinted genes. Nature 2002; 415: 810–13.Google Scholar
123Tilghman, SM. The sins of the fathers and mothers: genomic imprinting in mammalian development. Cell. 1999; 96: 185–93.Google Scholar
124Li, E, Bestor, TH, Jaenisch, R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 1992; 69: 915–26.Google Scholar
125Howell, CY, Bestor, TH, Ding, F, Latham, KE, Mertineit, C, Trasler, JM, et al. Genomic Imprinting Disrupted by a Maternal Effect Mutation in the Dnmt1 Gene. Cell 2001; 104: 829–38.Google Scholar
126Caspary, T, Cleary, MA, Perlman, EJ, Zhang, P, Elledge, SJ, Tilghman, SM. Oppositely imprinted genes p57(Kip2) and igf2 interact in a mouse model for Beckwith-Wiedemann syndrome. Genes Dev 1999; 13: 3115–24.Google Scholar
127Coan, PM, Burton, GJ, Ferguson-Smith, AC. Imprinted genes in the placenta–a review. Placenta 2005; 26 Suppl A: S10–20.Google Scholar
128Joyce, CA, Sharp, A, Walker, JM, Bullman, H, Temple, IK. Duplication of 7p12.1-p13, including GRB10 and IGFBP1, in a mother and daughter with features of Silver-Russell syndrome. Hum Genet 1999; 105: 273–80.Google Scholar
129Shiura, H, Nakamura, K, Hikichi, T, Hino, T, Oda, K, Suzuki-Migishima, R, et al. Paternal deletion of Meg1/Grb10 DMR causes maternalization of the Meg1/Grb10 cluster in mouse proximal Chromosome 11 leading to severe pre- and postnatal growth retardation. Hum Mol Genet 2009; 18: 1424–38.Google Scholar
130Eggermann, T, Wollmann, HA, Kuner, R, Eggermann, K, Enders, H, Kaiser, P, et al. Molecular studies in 37 Silver-Russell syndrome patients: frequency and etiology of uniparental disomy. Hum Genet 1997; 100: 415–19.Google Scholar
131Kotzot, D, Balmer, D, Baumer, A, Chrzanowska, K, Hamel, BC, Ilyina, H, et al. Maternal uniparental disomy 7–review and further delineation of the phenotype. Eur J Pediatr 2000; 159: 247–56.Google Scholar
132Nakabayashi, K, Fernandez, BA, Teshima, I, Shuman, C, Proud, VK, Curry, CJ, et al. Molecular genetic studies of human chromosome 7 in Russell-Silver syndrome. Genomics 2002; 79: 186–96.Google Scholar
133Eggermann, T, Schonherr, N, Meyer, E, Obermann, C, Mavany, M, Eggermann, K, et al. Epigenetic mutations in 11p15 in Silver-Russell syndrome are restricted to the telomeric imprinting domain. J Med Genet 2006; 43: 615–16.Google Scholar
134Bliek, J, Terhal, P, Van Den Bogaard, MJ, Maas, S, Hamel, B, Salieb-Beugelaar, G, et al. Hypomethylation of the H19 gene causes not only Silver-Russell syndrome (SRS) but also isolated asymmetry or an SRS-like phenotype. Am J Hum Genet 2006; 78: 604–14.CrossRefGoogle Scholar
135Schonherr, N, Meyer, E, Eggermann, K, Ranke, MB, Wollmann, HA, Eggermann, T. (Epi)mutations in 11p15 significantly contribute to Silver-Russell syndrome: but are they generally involved in growth retardation? Eur J Med Genet 2006; 49: 414–18.Google Scholar
136Bartholdi, D, Krajewska-Walasek, M, Ounap, K, Gaspar, H, Chrzanowska, KH, Ilyana, H, et al. Epigenetic mutations of the imprinted IGF2-H19 domain in Silver-Russell syndrome (SRS): results from a large cohort of patients with SRS and SRS-like phenotypes. J Med Genet 2009; 46: 192–97.Google Scholar
137Yamazawa, K, Kagami, M, Nagai, T, Kondoh, T, Onigata, K, Maeyama, K, et al. Molecular and clinical findings and their correlations in Silver-Russell syndrome: implications for a positive role of IGF2 in growth determination and differential imprinting regulation of the IGF2-H19 domain in bodies and placentas. J Mol Med 2008; 86: 1171–81.Google Scholar
138Yu, L, Chen, M, Zhao, D, Yi, P, Lu, L, Han, J, et al. The H19 Gene Imprinting in Normal Pregnancy and Pre-eclampsia. Placenta 2009; 30: 443–47.Google Scholar
139Bourque, DK, Avila, L, Penaherrera, M, von Dadelszen, P, Robinson, WP. Decreased Placental Methylation at the H19/IGF2 Imprinting Control Region is Associated with Normotensive Intrauterine Growth Restriction but not Preeclampsia. Placenta 2010; 31: 197–202.CrossRefGoogle Scholar
140Haycock, PC, Ramsay, M. Exposure of mouse embryos to ethanol during preimplantation development: effect on DNA methylation in the h19 imprinting control region. Biol Reprod 2009; 81: 618–27.Google Scholar
141McMinn, J, Wei, M, Schupf, N, Cusmai, J, Johnson, EB, Smith, AC et al. , Unbalanced Placental Expression of Imprinted Genes in Human Intrauterine Growth Restriction. Placenta 2006; 27: 540–49.Google Scholar
142Diplas, AI, Lambertini, L, Lee, MJ, Sperling, R, Lee, YL, Wetmur, J, et al. Differential expression of imprinted genes in normal and IUGR human placentas. Epigenetics 2009; 4; 235–40.Google Scholar
143Lambertini, L, Diplas, AI, Lee, MJ, Sperling, R, Chen, J, Wetmur, J. A sensitive functional assay reveals frequent loss of genomic imprinting in human placenta. Epigenetics 2008; 3: 261–69.Google Scholar
144Mendell, JT. miRiad roles for the miR-17–92 cluster in development and disease. Cell 2008; 133: 217–22.Google Scholar
145Pineles, BL, Romero, R, Montenegro, D, Tarca, AL, Han, YM, Kim, YM, et al. Distinct subsets of microRNAs are expressed differentially in the human placentas of patients with preeclampsia. Am J Obstet Gynecol 2007; 196: 261.Google Scholar
146Zhu, XM, Han, T, Sargent, IL, Yin, GW, Yao, YQ. Differential expression profile of microRNAs in human placentas from preeclamptic pregnancies vs normal pregnancies. Am J Obstet Gynecol 2009; 200: 661.Google Scholar
147Barker, DJ, Osmond, C, Forsen, TJ, Kajantie, E, Eriksson, JG. Trajectories of growth among children who have coronary events as adults. N Engl J Med 2005; 353: 1802–809.Google Scholar
148Barker, DJ. The developmental origins of chronic adult disease. Acta Paediatr Suppl 2004; 93: 26–33.Google Scholar
149Barker, DJ, Osmond, C, Forsen, TJ, Kajantie, E, Eriksson, JG. Maternal and social origins of hypertension. Hypertension 2007; 50: 565–71.Google Scholar
150Forsen, T, Eriksson, JG, Tuomilehto, J, Teramo, K, Osmond, C, Barker, DJ. Mother's weight in pregnancy and coronary heart disease in a cohort of Finnish men: follow up study. Br Med J 1997; 315: 837–40.Google Scholar
151Barker, DJ, Eriksson, JG, Forsen, T, Osmond, C. Fetal origins of adult disease: strength of effects and biological basis. Int J Epidemiol 2002; 31: 1235–239.Google Scholar
152Singhal, A, Cole, TJ, Fewtrell, M, Kennedy, K, Stephenson, T, Elias-Jones, A, et al. Promotion of faster weight gain in infants born small for gestational age: is there an adverse effect on later blood pressure? Circulation 2007; 115: 213–20.Google Scholar
153Eriksson, JG, Forsen, T, Tuomilehto, J, Osmond, C, Barker, DJ. Early growth and coronary heart disease in later life: longitudinal study. Br Med J 2001; 322: 949–53.Google Scholar
154Eriksson, H.A case report. H2-antagonist efficient against drug-related weight gain. Lakartidningen 2000; 97: 2869.Google Scholar
155Singhal, A, Lucas, A. Early origins of cardiovascular disease: is there a unifying hypothesis? Lancet 2004; 363: 1642–45.Google Scholar
156Brodszki, J, Lanne, T, Marsal, K, Ley, D. Impaired vascular growth in late adolescence after intrauterine growth restriction. Circulation. 2005; 111: 2623–628.Google Scholar
157Bjornsson, HT, Fallin, MD, Feinberg, AP. An integrated epigenetic and genetic approach to common human disease. Trends Genet 2004; 20: 350–58.Google Scholar
158Weksberg, R, Smith, AC, Squire, J, Sadowski, P. Beckwith-Wiedemann syndrome demonstrates a role for epigenetic control of normal development. Hum Mol Genet 2003; 12: R61–8.Google Scholar
159Dolinoy, DC, Weidman, JR, Jirtle, RL. Epigenetic gene regulation: linking early developmental environment to adult disease. Reprod Toxicol 2007; 23: 297–307.Google Scholar
160Cutfield, WS, Hofman, PL, Mitchell, M, Morison, IM. Could epigenetics play a role in the developmental origins of health and disease? Pediatr Res 2007; 61: 68R–75R.Google Scholar
161Shen, L, Kondo, Y, Guo, Y, Zhang, J, Zhang, L, Ahmed, S, et al. Genome-Wide Profiling of DNA Methylation Reveals a Class of Normally Methylated CpG Island Promoters. PLoS Genetics 2007; 3: e181.Google Scholar
162Lane, RH, Kelley, DE, Gruetzmacher, EM, Devaskar, SU. Uteroplacental insufficiency alters hepatic fatty acid-metabolizing enzymes in juvenile and adult rats. Am J Physiol Regul Integr Comp Physiol 2001; 280: R183–90.Google Scholar
163Simmons, RA, Templeton, LJ, Gertz, SJ. Intrauterine growth retardation leads to the development of type 2 diabetes in the rat. Diabetes 2001; 50: 2279–86.Google Scholar
164MacLennan, NK, James, SJ, Melnyk, S, Piroozi, A, Jernigan, S, Hsu, JL, et al. Uteroplacental insufficiency alters DNA methylation, one-carbon metabolism, and histone acetylation in IUGR rats. Physiol Genomics 2004; 18: 43–50.Google Scholar
165Fu, Q, McKnight, RA, Yu, X, Wang, L, Callaway, CW, Lane, RH. Uteroplacental insufficiency induces site-specific changes in histone H3 covalent modifications and affects DNA-histone H3 positioning in day 0 IUGR rat liver. Physiol Genomics 2004; 20: 108–16.Google Scholar
166Fu, Q, Yu, X, Callaway, CW, Lane, RH, McKnight, RA. Epigenetics: intrauterine growth retardation (IUGR) modifies the histone code along the rat hepatic IGF-1 gene. FASEB J 2009; 23: 2438–49.Google Scholar
167Fu, Q, McKnight, RA, Yu, X, Callaway, CW, Lane, RH. Growth retardation alters the epigenetic characteristics of hepatic dual specificity phosphatase 5. FASEB J 2006; 20: 2127–129.Google Scholar
168Ke, X, Lei, Q, James, SJ, Kelleher, SL, Melnyk, S, Jernigan, S, et al. Uteroplacental insufficiency affects epigenetic determinants of chromatin structure in brains of neonatal and juvenile IUGR rats. Physiol Genomics 2006; 25: 16–28.Google Scholar
169Park, JH, Stoffers, DA, Nicholls, RD, Simmons, RA. Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1. J Clin Invest 2008; 118: 2316–324.Google Scholar
170Raychaudhuri, N, Raychaudhuri, S, Thamotharan, M, Devaskar, SU. Histone code modifications repress glucose transporter 4 expression in the intrauterine growth-restricted offspring. J Biol Chem 2008; 283: 13611–626.Google Scholar
171Aagaard-Tillery, KM, Grove, K, Bishop, J, Ke, X, Fu, Q, McKnight, R, et al. Developmental origins of disease and determinants of chromatin structure: maternal diet modifies the primate fetal epigenome. J Mol Endocrinol 2008; 41: 91–102.Google Scholar
172Lumey, LH, Stein, AD. Offspring birth weights after maternal intrauterine undernutrition: a comparison within sibships. Am J Epidemiol 1997; 146: 810–19.Google Scholar