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Oogenesis pp 151-167 | Cite as

Epigenetic Regulation of Oocyte Function and Developmental Potential

  • Wendy DeanEmail author
Chapter

Abstract

Epigenetic regulation is complex, integrating transcriptional states of chromatin together with structural information influencing function and genome integrity. Some of these modifications are temporal lasting minutes or hours while others are heritable. The DNA content of all nucleated cells in an organism is nearly identical yet myriad cell types derive from the zygote, having followed the blueprint to generate all cell types of the adult. The orderly unfurling of this program of development with progressively restricted cellular plasticity, while maintaining cellular identity, requires mechanisms that uphold these heritable changes. Remarkably within these strict guidelines the germline and the early embryo reprogram their epigenetic information to restore pluripotency. While detailed information is not yet available for high-resolution analysis of chromatin profiles focussing on histone modifications, great advances have been made investigating DNA modifications during oogenesis and early development. These studies confirmed that differentially methylated regions, well beyond the cohort of imprinted genes, were affected with >1000 CpG islands acquiring their DNA methylation late in oogenesis. Moreover, in the mouse, as many as 15% of these methylated targets are maintained up to the blastocyct stage and are hence transgenerationally inherited. These reprogramming periods may be particularly sensitive to environmental disturbance and nutritional states making procedures such as those in the treatment of human infertility especially susceptible to epigenetic alterations that may be inherited and transmitted to future generations. This chapter describes some of the most important aspects and exciting new discoveries in epigenetic regulation in oocytes and embryos and highlights their implications in the treatment of human infertility by assisted reproductive technologies.

Keywords

Epigenetic Oocyte Reprogramming DNA methylation Transgenerational inheritance 

References

  1. 1.
    Waddington CH. Organisers and genes. Cambridge: Cambridge University Press; 1940.Google Scholar
  2. 2.
    Youngson NA, Whitelaw E. Transgenerational epigenetic effects. Annu Rev Genomics Hum Genet. 2008;9:233–57.PubMedGoogle Scholar
  3. 3.
    Robertson KD, Wolffe AP. DNA methylation in health and disease. Nat Rev Genet. 2000;1:11–9.PubMedGoogle Scholar
  4. 4.
    Hemberger M, Dean W, Reik W. Epigenetic dynamics of stem cells and cell lineage commitment: digging Waddington’s canal. Nat Rev Mol Cell Biol. 2009;10:526–37.PubMedGoogle Scholar
  5. 5.
    Ahmad K, Henikoff S. The histone variant H3.3 marks active chromatin by replication-independent nucleosome assembly. Mol Cell. 2002;9:1191–200.PubMedGoogle Scholar
  6. 6.
    Ahmad K, Henikoff S. Histone H3 variants specify modes of chromatin assembly. Proc Natl Acad Sci USA. 2002;99 Suppl 4:16477–84.PubMedGoogle Scholar
  7. 7.
    Law JA, Jacobsen SE. Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nat Rev Genet. 2010;11:204–20.PubMedGoogle Scholar
  8. 8.
    Turner BM. Histone acetylation and an epigenetic code. Bioessays. 2000;22:836–45.PubMedGoogle Scholar
  9. 9.
    Turner BM. Defining an epigenetic code. Nat Cell Biol. 2007;9:2–6.PubMedGoogle Scholar
  10. 10.
    Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000;403:41–5.PubMedGoogle Scholar
  11. 11.
    Jenuwein T, Allis CD. Translating the histone code. Science. 2001;293:1074–80.PubMedGoogle Scholar
  12. 12.
    Lachner M, Jenuwein T. The many faces of histone lysine methylation. Curr Opin Cell Biol. 2002;14:286–98.PubMedGoogle Scholar
  13. 13.
    Schotta G, Lachner M, Sarma K, Ebert A, Sengupta R, Reuter G, et al. A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin. Genes Dev. 2004;18:1251–62.PubMedGoogle Scholar
  14. 14.
    Santenard A, Torres-Padilla ME. Epigenetic reprogramming in mammalian reproduction: contribution from histone variants. Epigenetics. 2009;4:80–4.PubMedGoogle Scholar
  15. 15.
    Perez-Burgos L, Peters AH, Opravil S, Kauer M, Mechtler K, Jenuwein T. Generation and characterization of methyl-lysine histone antibodies. Methods Enzymol. 2004;376:234–54.PubMedGoogle Scholar
  16. 16.
    Reik W, Santos F, Mitsuya K, Morgan H, Dean W. Epigenetic asymmetry in the mammalian zygote and early embryo: relationship to lineage commitment? Philos Trans R Soc Lond B Biol Sci. 2003;358:1403–9, discussion 9.PubMedGoogle Scholar
  17. 17.
    Becker M, Becker A, Miyara F, Han Z, Kihara M, Brown DT, et al. Differential in vivo binding dynamics of somatic and oocyte-specific linker histones in oocytes and during ES cell nuclear transfer. Mol Biol Cell. 2005;16:3887–95.PubMedGoogle Scholar
  18. 18.
    Reik W, Dean W, Walter J. Epigenetic reprogramming in mammalian development. Science. 2001;293:1089–93.PubMedGoogle Scholar
  19. 19.
    Sasaki H, Matsui Y. Epigenetic events in mammalian germ-cell development: reprogramming and beyond. Nat Rev Genet. 2008;9:129–40.PubMedGoogle Scholar
  20. 20.
    Li E. Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev Genet. 2002;3:662–73.PubMedGoogle Scholar
  21. 21.
    Santos F, Dean W. Epigenetic reprogramming during early development in mammals. Reproduction. 2004;127:643–51.PubMedGoogle Scholar
  22. 22.
    McLay DW, Clarke HJ. Remodelling the paternal chromatin at fertilization in mammals. Reproduction. 2003;125:625–33.PubMedGoogle Scholar
  23. 23.
    Monk M, Boubelik M, Lehnert S. Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development. Development. 1987;99:371–82.PubMedGoogle Scholar
  24. 24.
    Kafri T, Ariel M, Brandeis M, Shemer R, Urven L, McCarrey J, et al. Developmental pattern of gene-specific DNA methylation in the mouse embryo and germ line. Genes Dev. 1992;6:705–14.PubMedGoogle Scholar
  25. 25.
    Rougier N, Bourc’his D, Gomes DM, Niveleau A, Plachot M, Paldi A, et al. Chromosome methylation patterns during mammalian preimplantation development. Genes Dev. 1998;12:2108–13.PubMedGoogle Scholar
  26. 26.
    Perreault SD. Chromatin remodeling in mammalian zygotes. Mutat Res. 1992;296:43–55.PubMedGoogle Scholar
  27. 27.
    Perreault SD, Zirkin BR. Sperm nuclear decondensation in mammals: role of sperm-associated proteinase in vivo. J Exp Zool. 1982;224:253–7.PubMedGoogle Scholar
  28. 28.
    van der Heijden GW, Dieker JW, Derijck AA, Muller S, Berden JH, Braat DD, et al. Asymmetry in histone H3 variants and lysine methylation between paternal and maternal chromatin of the early mouse zygote. Mech Dev. 2005;122:1008–22.PubMedGoogle Scholar
  29. 29.
    Oswald J, Engemann S, Lane N, Mayer W, Olek A, Fundele R, et al. Active demethylation of the paternal genome in the mouse zygote. Curr Biol. 2000;10:475–8.PubMedGoogle Scholar
  30. 30.
    Santos F, Hendrich B, Reik W, Dean W. Dynamic reprogramming of DNA methylation in the early mouse embryo. Dev Biol. 2002;241:172–82.PubMedGoogle Scholar
  31. 31.
    Santos F, Peters AH, Otte AP, Reik W, Dean W. Dynamic chromatin modifications characterise the first cell cycle in mouse embryos. Dev Biol. 2005;280:225–36.PubMedGoogle Scholar
  32. 32.
    Puschendorf M, Terranova R, Boutsma E, Mao X, Isono K, Brykczynska U, et al. PRC1 and Suv39h specify parental asymmetry at constitutive heterochromatin in early mouse embryos. Nat Genet. 2008;40:411–20.PubMedGoogle Scholar
  33. 33.
    Probst AV, Santos F, Reik W, Almouzni G, Dean W. Structural differences in centromeric heterochromatin are spatially reconciled on fertilisation in the mouse zygote. Chromosoma. 2007;116:403–15.PubMedGoogle Scholar
  34. 34.
    Guenatri M, Bailly D, Maison C, Almouzni G. Mouse centric and pericentric satellite repeats form distinct functional heterochromatin. J Cell Biol. 2004;166:493–505.PubMedGoogle Scholar
  35. 35.
    Adenot PG, Mercier Y, Renard JP, Thompson EM. Differential H4 acetylation of paternal and maternal chromatin precedes DNA replication and differential transcriptional activity in pronuclei of 1-cell mouse embryos. Development. 1997;124:4615–25.PubMedGoogle Scholar
  36. 36.
    Arney KL, Bao S, Bannister AJ, Kouzarides T, Surani MA. Histone methylation defines epigenetic asymmetry in the mouse zygote. Int J Dev Biol. 2002;46:317–20.PubMedGoogle Scholar
  37. 37.
    Morgan HD, Santos F, Green K, Dean W, Reik W. Epigenetic reprogramming in mammals. Hum Mol Genet. 2005;14(Spec No 1):R47–58.PubMedGoogle Scholar
  38. 38.
    Schneider J, Shilatifard A. Histone demethylation by hydroxylation: chemistry in action. ACS Chem Biol. 2006;1:75–81.PubMedGoogle Scholar
  39. 39.
    Nashun B, Yukawa M, Liu H, Akiyama T, Aoki F. Changes in the nuclear deposition of histone H2A variants during pre-implantation development in mice. Development. 2010;137:3785–94.PubMedGoogle Scholar
  40. 40.
    Akiyama T, Suzuki O, Matsuda J, Aoki F. Dynamic replacement of histone H3 variants reprograms epigenetic marks in early mouse embryos. PLoS Genet. 2011;7:e1002279.PubMedGoogle Scholar
  41. 41.
    Santenard A, Ziegler-Birling C, Koch M, Tora L, Bannister AJ, Torres-Padilla ME. Heterochromatin formation in the mouse embryo requires critical residues of the histone variant H3.3. Nat Cell Biol. 2010;12:853–62.PubMedGoogle Scholar
  42. 42.
    Daujat S, Weiss T, Mohn F, Lange UC, Ziegler-Birling C, Zeissler U, et al. H3K64 trimethylation marks heterochromatin and is dynamically remodeled during developmental reprogramming. Nat Struct Mol Biol. 2009;16:777–81.PubMedGoogle Scholar
  43. 43.
    Kouzarides T. Chromatin modifications and their function. Cell. 2007;128:693–705.PubMedGoogle Scholar
  44. 44.
    Trasler JM, Alcivar AA, Hake LE, Bestor T, Hecht NB. DNA methyltransferase is developmentally expressed in replicating and non-replicating male germ cells. Nucleic Acids Res. 1992;20:2541–5.PubMedGoogle Scholar
  45. 45.
    Bourc’his D, Xu GL, Lin CS, Bollman B, Bestor TH. Dnmt3L and the establishment of maternal genomic imprints. Science. 2001;294:2536–9.PubMedGoogle Scholar
  46. 46.
    Hajkova P, Erhardt S, Lane N, Haaf T, El-Maarri O, Reik W, et al. Epigenetic reprogramming in mouse primordial germ cells. Mech Dev. 2002;117:15–23.PubMedGoogle Scholar
  47. 47.
    Lee J, Inoue K, Ono R, Ogonuki N, Kohda T, Kaneko-Ishino T, et al. Erasing genomic imprinting memory in mouse clone embryos produced from day 11.5 primordial germ cells. Development. 2002;129:1807–17.PubMedGoogle Scholar
  48. 48.
    Yamazaki Y, Mann MR, Lee SS, Marh J, McCarrey JR, Yanagimachi R, et al. Reprogramming of primordial germ cells begins before migration into the genital ridge, making these cells inadequate donors for reproductive cloning. Proc Natl Acad Sci USA. 2003;100:12207–12.PubMedGoogle Scholar
  49. 49.
    Popp C, Dean W, Feng S, Cokus SJ, Andrews S, Pellegrini M, et al. Genome- wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency. Nature. 2010;463:1101–5.PubMedGoogle Scholar
  50. 50.
    Smallwood SA, Tomizawa S, Krueger F, Ruf N, Carli N, Segonds-Pichon A, et al. Dynamic CpG island methylation landscape in oocytes and preimplantation embryos. Nat Genet. 2011;43:811–4.PubMedGoogle Scholar
  51. 51.
    Ciccone DN, Su H, Hevi S, Gay F, Lei H, Bajko J, et al. KDM1B is a histone H3K4 demethylase required to establish maternal genomic imprints. Nature. 2009;461:415–8.PubMedGoogle Scholar
  52. 52.
    Quenneville S, Verde G, Corsinotti A, Kapopoulou A, Jakobsson J, Offner S, et al. In embryonic stem cells, ZFP57/KAP1 recognize a methylated hexanucleotide to affect chromatin and DNA methylation of imprinting control regions. Mol Cell. 2011;44:361–72.PubMedGoogle Scholar
  53. 53.
    Hiura H, Obata Y, Komiyama J, Shirai M, Kono T. Oocyte growth-dependent progression of maternal imprinting in mice. Genes Cells. 2006;11:353–61.PubMedGoogle Scholar
  54. 54.
    Hata K, Okano M, Lei H, Li E. Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice. Development. 2002;129:1983–93.PubMedGoogle Scholar
  55. 55.
    Kaneda M, Okano M, Hata K, Sado T, Tsujimoto N, Li E, et al. Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature. 2004;429:900–3.PubMedGoogle Scholar
  56. 56.
    Smallwood SA, Kelsey G. De novo DNA methylation: a germ cell perspective. Trends Genet. 2012;28:33–42.PubMedGoogle Scholar
  57. 57.
    Chotalia M, Smallwood SA, Ruf N, Dawson C, Lucifero D, Frontera M, et al. Transcription is required for establishment of germline methylation marks at imprinted genes. Genes Dev. 2009;23:105–17.PubMedGoogle Scholar
  58. 58.
    Li X, Ito M, Zhou F, Youngson N, Zuo X, Leder P, et al. A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints. Dev Cell. 2008;15:547–57.PubMedGoogle Scholar
  59. 59.
    Ideraabdullah FY, Bartolomei MS. ZFP57: KAPturing DNA methylation at imprinted loci. Mol Cell. 2011;44:341–2.PubMedGoogle Scholar
  60. 60.
    Lucifero D, Mann MR, Bartolomei MS, Trasler JM. Gene-specific timing and epigenetic memory in oocyte imprinting. Hum Mol Genet. 2004;13:839–49.PubMedGoogle Scholar
  61. 61.
    Sekita Y, Wagatsuma H, Nakamura K, Ono R, Kagami M, Wakisaka N, et al. Role of retrotransposon-derived imprinted gene, Rtl1, in the feto-maternal interface of mouse placenta. Nat Genet. 2008;40:243–8.PubMedGoogle Scholar
  62. 62.
    Rawn SM, Cross JC. The evolution, regulation, and function of placenta- specific genes. Annu Rev Cell Dev Biol. 2008;24:159–81.PubMedGoogle Scholar
  63. 63.
    Brown JD, Piccuillo V, O’Neill RJ. Retroelement demethylation associated with abnormal placentation in Mus musculus x Mus caroli hybrids. Biol Reprod. 2012;86:88.PubMedGoogle Scholar
  64. 64.
    Dean W, Santos F, Reik W. Epigenetic reprogramming in early mammalian development and following somatic nuclear transfer. Semin Cell Dev Biol. 2003;14:93–100.PubMedGoogle Scholar
  65. 65.
    Ramsahoye BH, Biniszkiewicz D, Lyko F, Clark V, Bird AP, Jaenisch R. Non- CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. Proc Natl Acad Sci USA. 2000;97:5237–42.PubMedGoogle Scholar
  66. 66.
    Tomizawa S, Kobayashi H, Watanabe T, Andrews S, Hata K, Kelsey G, et al. Dynamic stage-specific changes in imprinted differentially methylated regions during early mammalian development and prevalence of non-CpG methylation in oocytes. Development. 2011;138:811–20.PubMedGoogle Scholar
  67. 67.
    Ooi SK, Bestor TH. The colorful history of active DNA demethylation. Cell. 2008;133:1145–8.PubMedGoogle Scholar
  68. 68.
    Niehrs C, Active DNA. Demethylation and DNA repair. Differentiation. 2009;77:1–11.PubMedGoogle Scholar
  69. 69.
    Fritz EL, Papavasiliou FN. Cytidine deaminases: AIDing DNA demethylation? Genes Dev. 2010;24:2107–14.PubMedGoogle Scholar
  70. 70.
    Teperek-Tkacz M, Pasque V, Gentsch G, Ferguson-Smith AC. Epigenetic reprogramming: is deamination key to active DNA demethylation? Reproduction. 2011;142:621–32.PubMedGoogle Scholar
  71. 71.
    Guo JU, Su Y, Zhong C, Ming GL, Song H. Emerging roles of TET proteins and 5-hydroxymethylcytosines in active DNA demethylation and beyond. Cell Cycle. 2011;10:2662–8.PubMedGoogle Scholar
  72. 72.
    Wu H, Zhang Y. Mechanisms and functions of Tet protein-mediated 5- methylcytosine oxidation. Genes Dev. 2011;25:2436–52.PubMedGoogle Scholar
  73. 73.
    Williams K, Christensen J, Helin K. DNA methylation: TET proteins-guardians of CpG islands? EMBO Rep. 2011;13:28–35.PubMedGoogle Scholar
  74. 74.
    Ito S, D’Alessio AC, Taranova OV, Hong K, Sowers LC, Zhang Y. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature. 2010;466:1129–33.PubMedGoogle Scholar
  75. 75.
    Iqbal K, Jin SG, Pfeifer GP, Szabo PE. Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine. Proc Natl Acad Sci USA. 2011;108:3642–7.PubMedGoogle Scholar
  76. 76.
    Wossidlo M, Nakamura T, Lepikhov K, Marques CJ, Zakhartchenko V, Boiani M, et al. 5-hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming. Nat Commun. 2011;2:241.PubMedGoogle Scholar
  77. 77.
    Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science. 2011;333:1300–3.PubMedGoogle Scholar
  78. 78.
    Inoue A, Shen L, Dai Q, He C, Zhang Y. Generation and replication-dependent dilution of 5fC and 5caC during mouse preimplantation development. Cell Res. 2011;21:1670–6.PubMedGoogle Scholar
  79. 79.
    Gu TP, Guo F, Yang H, Wu HP, Xu GF, Liu W, et al. The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature. 2011;477:606–10.PubMedGoogle Scholar
  80. 80.
    Inoue A, Zhang Y. Replication-dependent loss of 5-hydroxymethylcytosine in mouse preimplantation embryos. Science. 2011;334:194.PubMedGoogle Scholar
  81. 81.
    Waterland RA, Jirtle RL. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol. 2003;23:5293–300.PubMedGoogle Scholar
  82. 82.
    Cropley JE, Suter CM, Beckman KB, Martin DI. Germ-line epigenetic modification of the murine A vy allele by nutritional supplementation. Proc Natl Acad Sci USA. 2006;103:17308–12.PubMedGoogle Scholar
  83. 83.
    Daxinger L, Whitelaw E. Understanding transgenerational epigenetic inheritance via the gametes in mammals. Nat Rev Genet. 2012;13:153–62.PubMedGoogle Scholar
  84. 84.
    Borgel J, Guibert S, Li Y, Chiba H, Schubeler D, Sasaki H, et al. Targets and dynamics of promoter DNA methylation during early mouse development. Nat Genet. 2010;42:1093–100.PubMedGoogle Scholar
  85. 85.
    DeBaun MR, Niemitz EL, Feinberg AP. Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19. Am J Hum Genet. 2003;72:156–60.PubMedGoogle Scholar
  86. 86.
    Gicquel C, Gaston V, Mandelbaum J, Siffroi JP, Flahault A, Le Bouc Y. In vitro fertilization may increase the risk of Beckwith-Wiedemann syndrome related to the abnormal imprinting of the KCN1OT gene. Am J Hum Genet. 2003;72:1338–41.PubMedGoogle Scholar
  87. 87.
    Maher ER, Afnan M, Barratt CL. Epigenetic risks related to assisted reproductive technologies: epigenetics, imprinting, ART and icebergs? Hum Reprod. 2003;18:2508–11.PubMedGoogle Scholar
  88. 88.
    Maher ER, Brueton LA, Bowdin SC, Luharia A, Cooper W, Cole TR, et al. Beckwith-Wiedemann syndrome and assisted reproduction technology (ART). J Med Genet. 2003;40:62–4.PubMedGoogle Scholar
  89. 89.
    Doornbos ME, Maas SM, McDonnell J, Vermeiden JP, Hennekam RC. Infertility, assisted reproduction technologies and imprinting disturbances: a Dutch study. Hum Reprod. 2007;22:2476–80.PubMedGoogle Scholar
  90. 90.
    Amor DJ, Halliday J. A review of known imprinting syndromes and their association with assisted reproduction technologies. Hum Reprod. 2008;23:2826–34.PubMedGoogle Scholar
  91. 91.
    Manipalviratn S, DeCherney A, Segars J. Imprinting disorders and assisted reproductive technology. Fertil Steril. 2009;91:305–15.PubMedGoogle Scholar
  92. 92.
    Market-Velker BA, Zhang L, Magri LS, Bonvissuto AC, Mann MR. Dual effects of superovulation: loss of maternal and paternal imprinted methylation in a dose-dependent manner. Hum Mol Genet. 2010;19:36–51.PubMedGoogle Scholar
  93. 93.
    Wilkins-Haug L. Epigenetics and assisted reproduction. Curr Opin Obstet Gynecol. 2009;21:201–6.PubMedGoogle Scholar
  94. 94.
    Ibala-Romdhane S, Al-Khtib M, Khoueiry R, Blachere T, Guerin JF, Lefevre A. Analysis of H19 methylation in control and abnormal human embryos, sperm and oocytes. Eur J Hum Genet. 2011;19:1138–43.PubMedGoogle Scholar
  95. 95.
    Horii T, Suetake I, Yanagisawa E, Morita S, Kimura M, Nagao Y, et al. The Dnmt3b splice variant is specifically expressed in in vitro-manipulated blastocysts and their derivative ES cells. J Reprod Dev. 2011;57:579–85.PubMedGoogle Scholar
  96. 96.
    Denomme MM, Zhang L, Mann MR. Embryonic imprinting perturbations do not originate from ­superovulation-induced defects in DNA methylation acquisition. Fertil Steril. 2011;96:734–8 e2.PubMedGoogle Scholar
  97. 97.
    Grace KS, Sinclair KD. Assisted reproductive technology, epigenetics, and long-term health: a ­developmental time bomb still ticking. Semin Reprod Med. 2009;27:409–16.PubMedGoogle Scholar
  98. 98.
    Savage T, Peek J, Hofman PL, Cutfield WS. Childhood outcomes of assisted reproductive technology. Hum Reprod. 2011;26:2392–400.PubMedGoogle Scholar
  99. 99.
    Chian RC. In-vitro maturation of immature oocytes for infertile women with PCOS. Reprod Biomed Online. 2004;8:547–52.PubMedGoogle Scholar
  100. 100.
    Sato A, Otsu E, Negishi H, Utsunomiya T, Arima T. Aberrant DNA methylation of imprinted loci in superovulated oocytes. Hum Reprod. 2007;22:26–35.PubMedGoogle Scholar
  101. 101.
    Hiendleder S, Wirtz M, Mund C, Klempt M, Reichenbach HD, Stojkovic M, et al. Tissue-specific effects of in vitro fertilization procedures on genomic cytosine methylation levels in overgrown and ­normal sized bovine fetuses. Biol Reprod. 2006;75:17–23.PubMedGoogle Scholar
  102. 102.
    Borghol N, Lornage J, Blachere T, Sophie Garret A, Lefevre A. Epigenetic status of the H19 locus in human oocytes following in vitro maturation. Genomics. 2006;87:417–26.PubMedGoogle Scholar
  103. 103.
    Watkins AJ, Wilkins A, Cunningham C, Perry VH, Seet MJ, Osmond C, et al. Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring. J Physiol. 2008;586:2231–44.PubMedGoogle Scholar
  104. 104.
    Kwong WY, Wild AE, Roberts P, Willis AC, Fleming TP. Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Development. 2000;127:4195–202.PubMedGoogle Scholar
  105. 105.
    Batcheller A, Cardozo E, Maguire M, DeCherney AH, Segars JH. Are there subtle genome-wide epigenetic alterations in normal offspring conceived by assisted reproductive technologies? Fertil Steril. 2011;96:1306–11.PubMedGoogle Scholar

Copyright information

© Springer-Verlag London 2013

Authors and Affiliations

  1. 1.Epigenetics ProgrammeThe Babraham InstituteCambridgeUK

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