Register      Login
Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

The role of early embryonic environment on epigenotype and phenotype

Nicola Vickaryous A and Emma Whitelaw A B
+ Author Affiliations
- Author Affiliations

A School of Molecular and Microbial Biosciences, University of Sydney, Sydney, NSW 2006, Australia.

B Corresponding author. Email: e.whitelaw@mmb.usyd.edu.au

Reproduction, Fertility and Development 17(3) 335-340 https://doi.org/10.1071/RD04133
Submitted: 9 November 2004  Accepted: 11 January 2005   Published: 14 February 2005

Abstract

The influence of epigenetic modifications to the genome on the phenotype of the adult organism is now a tractable problem in biology. This has come about through the development of methods that enable us to study the methylation state of the DNA and the packaging of the chromatin at specific gene loci. It is becoming clear that early embryogenesis is a critical period for the establishment of the epigenotype. Furthermore, it appears that this process is sensitive to environmental conditions. This is a concern in light of the increasing use of artificial reproductive technologies throughout the world.


References

Barker, D. J. (1995). Fetal origins of coronary heart disease. BMJ 311, 171–174.
PubMed |

BenEzra, D. (2003). In vitro fertilisation and retinoblastoma. Lancet 361, 273–274.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Bird, A. (2002). DNA methylation patterns and epigenetic memory. Genes Dev. 16, 6–21.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Cavalli, G. , and Paro, R. (1998). The Drosophila Fab-7 chromosomal element conveys epigenetic inheritance during mitosis and meiosis. Cell 93, 505–518.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Cheng, M. K. , and Disteche, C. M. (2004). Silence of the fathers: early X inactivation. Bioessays 26, 821–824.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Cox, G. F. , Burger, J. , Lip, V. , Mau, U. A. , Sperling, K. , Wu, B. L. , and Horsthemke, B. (2002). Intracytoplasmic sperm injection may increase the risk of imprinting defects. Am. J. Hum. Genet. 71, 162–164.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Curley, J. P. , Barton, S. , Surani, A. , and Keverne, E. B. (2004). Coadaptation in mother and infant regulated by a paternally expressed imprinted gene. Proc. R. Soc. Lond. B. Biol. Sci. 271, 1303–1309.
Crossref | GoogleScholarGoogle Scholar | PubMed |

DeBaun, M. R. , Niemitz, E. L. , and Feinberg, A. P. (2003). Association of in vitro fertilization with Beckwith–Wiedemann syndrome and epigenetic alterations of LIT1 and H19. Am. J. Hum. Genet. 72, 156–160.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Delaval, K. , and Feil, R. (2004). Epigenetic regulation of mammalian genomic imprinting. Curr. Opin. Genet. Dev. 14, 188–195.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Doherty, A. S. , Mann, M. R. , Tremblay, K. D. , Bartolomei, M. S. , and Schultz, R. M. (2000). Differential effects of culture on imprinted H19 expression in the preimplantation mouse embryo. Biol. Reprod. 62, 1526–1535.
PubMed |

Drake, A. J. , Walker, B. R. , and Seckl, J. R. (2005). Intergenerational consequences of fetal programming by in utero exposure to glucocorticoids in rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 288, 34–38.


Feinberg, A. P. , and Tycko, B. (2004). The history of cancer epigenetics. Nat. Rev. Cancer 4, 143–153.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Fernandez-Gonzalez, R. , Moreira, P. , Bilbao, A. , Jimenez, A. , Perez-Crespo, M. , Ramirez, M. A. , Rodriguez De Fonseca, F. , Pintado, B. , and Gutierrez-Adan, A. (2004). Long-term effect of in vitro culture of mouse embryos with serum on mRNA expression of imprinting genes, development, and behavior. Proc. Natl Acad. Sci. USA 101, 5880–5885.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Fournier, C. , Goto, Y. , Ballestar, E. , Delaval, K. , Hever, A. M. , Esteller, M. , and Feil, R. (2002). Allele-specific histone lysine methylation marks regulatory regions at imprinted mouse genes. EMBO J. 21, 6560–6570.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Fowden, A. L. (2003). The insulin-like growth factors and feto-placental growth. Placenta 24, 803–812.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Godfrey, K. M. , and Barker, D. J. (2000). Fetal nutrition and adult disease. Am. J. Clin. Nutr. 71, 1344S–1352S.
PubMed |

Halliday, J. , Oke, K. , Breheny, S. , Algar, E. , and Amor, D. (2004). Beckwith–Wiedemann syndrome and IVF: a case-control study. Am. J. Hum. Genet. 75, 526–528.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Han, Y. M. , Kang, Y. K. , Koo, D. B. , and Lee, K. K. (2003). Nuclear reprogramming of cloned embryos produced in vitro. Theriogenology 59, 33–44.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Hendrich, B. , and Tweedie, S. (2003). The methyl-CpG binding domain and the evolving role of DNA methylation in animals. Trends Genet. 19, 269–277.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Hendrich, B. , Guy, J. , Ramsahoye, B. , Wilson, V. A. , and Bird, A. (2001). Closely related proteins MBD2 and MBD3 play distinctive but interacting roles in mouse development. Genes Dev. 15, 710–723.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Hollick, J. B. , Patterson, G. I. , Coe, E. H. , Cone, K. C. , and Chandler, V. L. (1995). Allelic interactions heritably alter the activity of a metastable maize pl allele. Genetics 141, 709–719.
PubMed |

Humpherys, D. , Eggan, K. , Akutsu, H. , Hochedlinger, K. , Rideout, W. M. , Biniszkiewicz, D. , Yanagimachi, R. , and Jaenisch, R. (2001). Epigenetic instability in ES cells and cloned mice. Science 293, 95–97.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Itier, J. M. , Tremp, G. L. , Leonard, J. F. , Multon, M. C. , Ret, G. , Schweighoffer, F. , Tocque, B. , Bluet-Pajot, M. T. , Cormier, V. , and Dautry, F. (1998). Imprinted gene in postnatal growth role. Nature 393, 125–126.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Kamath, B. M. , Krantz, I. D. , Spinner, N. B. , Heubi, J. E. , and Piccoli, D. A. (2002). Monozygotic twins with a severe form of Alagille syndrome and phenotypic discordance. Am. J. Med. Genet. 112, 194–197.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Kanduri, C. , Pant, V. , Loukinov, D. , Pugacheva, E. , Qi, C. F. , Wolffe, A. , Ohlsson, R. , and Lobanenkov, V. V. (2000). Functional association of CTCF with the insulator upstream of the H19 gene is parent of origin-specific and methylation-sensitive. Curr. Biol. 10, 853–856.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Khosla, S. , Dean, W. , Brown, D. , Reik, W. , and Feil, R. (2001). Culture of preimplantation mouse embryos affects fetal development and the expression of imprinted genes. Biol. Reprod. 64, 918–926.
PubMed |

Kim, J. , Kollhoff, A. , Bergmann, A. , and Stubbs, L. (2003). Methylation-sensitive binding of transcription factor YY1 to an insulator sequence within the paternally expressed imprinted gene, Peg3. Hum. Mol. Genet. 12, 233–245.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Lachmann, R. H. , Grant, I. R. , Halsall, D. , and Cox, T. M. (2004). Twin pairs showing discordance of phenotype in adult Gaucher’s disease. QJM 97, 199–204.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Lachner, M. , O’Sullivan, R. J. , and Jenuwein, T. (2003). An epigenetic road map for histone lysine methylation. J. Cell Sci. 116, 2117–2124.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Lander, E. S. , Linton, L. M. , Birren, B. , Nusbaum, C. , and Zody, M. C. , et al. (2001). Initial sequencing and analysis of the human genome. Nature 409, 860–921.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Lane, N. , Dean, W. , Erhardt, S. , Hajkova, P. , Surani, A. , Walter, J. , and Reik, W. (2003). Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis 35, 88–93.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Lonergan, P. , Rizos, D. , Gutierrez-Adan, A. , Moreira, P. M. , Pintado, B. , de la Fuente, J. , and Boland, M. P. (2003). Temporal divergence in the pattern of messenger RNA expression in bovine embryos cultured from the zygote to blastocyst stage in vitro or in vivo. Biol. Reprod. 69, 1424–1431.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Lund, A. H. , and van Lohuizen, M. (2004). Epigenetics and cancer. Genes Dev. 18, 2315–2335.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Mann, M. R. , Lee, S. S. , Doherty, A. S. , Verona, R. I. , Nolen, L. D. , Schultz, R. M. , and Bartolomei, M. S. (2004). Selective loss of imprinting in the placenta following preimplantation development in culture. Development 131, 3727–3735.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Mayer, W. , Niveleau, A. , Walter, J. , Fundele, R. , and Haaf, T. (2000). Demethylation of the zygotic paternal genome. Nature 403, 501–502.
PubMed |

Moll, A. C. , Imhof, S. M. , Cruysberg, J. R. , Schouten-van Meeteren, A. Y. , Boers, M. , and van Leeuwen, F. E. (2003). Incidence of retinoblastoma in children born after in vitro fertilisation. Lancet 361, 309–310.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Monk, M. , Boubelik, M. , and Lehnert, S. (1987). Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development. Development 99, 371–382.
PubMed |

Moore, T. , and Reik, W. (1996). Genetic conflict in early development: parental imprinting in normal and abnormal growth. Rev. Reprod. 1, 73–77.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Morgan, H. D. , Sutherland, H. G. , Martin, D. I. , and Whitelaw, E. (1999). Epigenetic inheritance at the agouti locus in the mouse. Nat. Genet. 23, 314–318.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Murphy, S. K. , Wylie, A. A. , and Jirtle, R. L. (2001). Imprinting of PEG3, the human homologue of a mouse gene involved in nurturing behavior. Genomics 71, 110–117.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Niemann, H. , and Wrenzycki, C. (2000). Alterations of expression of developmentally important genes in preimplantation bovine embryos by in vitro culture conditions: implications for subsequent development. Theriogenology 53, 21–34.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Niemitz, E. L. , and Feinberg, A. P. (2004). Epigenetics and assisted reproductive technology: a call for investigation. Am. J. Hum. Genet. 74, 599–609.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Ogawa, H. , Ono, Y. , Shimozawa, N. , Sotomaru, Y. , Katsuzawa, Y. , Hiura, H. , Ito, M. , and Kono, T. (2003). Disruption of imprinting in cloned mouse fetuses from embryonic stem cells. Reproduction 126, 549–557.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Oswald, J. , Engemann, S. , Lane, N. , Mayer, W. , Olek, A. , Fundele, R. , Dean, W. , Reik, W. , and Walter, J. (2000). Active demethylation of the paternal genome in the mouse zygote. Curr. Biol. 10, 475–478.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Petronis, A. (2003). Epigenetics and bipolar disorder: new opportunities and challenges. Am. J. Med. Genet. 123C, 65–75.
Crossref | GoogleScholarGoogle Scholar |

Rakyan, V. K. , Blewitt, M. E. , Druker, R. , Preis, J. I. , and Whitelaw, E. (2002). Metastable epialleles in mammals. Trends Genet. 18, 348–351.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Rakyan, V. K. , Chong, S. , Champ, M. E. , Cuthbert, P. C. , Morgan, H. D. , Luu, K. V. , and Whitelaw, E. (2003). Transgenerational inheritance of epigenetic states at the murine AxinFu allele occurs after maternal and paternal transmission. Proc. Natl Acad. Sci. USA 100, 2538–2543.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Reik, W. , Constancia, M. , Fowden, A. , Anderson, N. , Dean, W. , Ferguson-Smith, A. , Tycko, B. , and Sibley, C. (2003). Regulation of supply and demand for maternal nutrients in mammals by imprinted genes. J. Physiol. 547, 35–44.
PubMed |

Rideout, W. M. , Eggan, K. , and Jaenisch, R. (2001). Nuclear cloning and epigenetic reprogramming of the genome. Science 293, 1093–1098.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Rinaudo, P. , and Schultz, R. M. (2004). Effects of embryo culture on global pattern of gene expression in preimplantation mouse embryos. Reproduction 128, 301–311.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Roseboom, T. J. , van der Meulen, J. H. , Ravelli, A. C. , Osmond, C. , Barker, D. J. , and Bleker, O. P. (2001). Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview. Twin Res. 4, 293–298.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Rougier, N. , Bourc’his, D. , Gomes, D. M. , Niveleau, A. , Plachot, M. , Paldi, A. , and Viegas-Pequignot, E. (1998). Chromosome methylation patterns during mammalian preimplantation development. Genes Dev. 12, 2108–2113.
PubMed |

Santos, F. , Hendrich, B. , Reik, W. , and Dean, W. (2002). Dynamic reprogramming of DNA methylation in the early mouse embryo. Dev. Biol. 241, 172–182.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Simonsson, S. , and Gurdon, J. (2004). DNA demethylation is necessary for the epigenetic reprogramming of somatic cell nuclei. Nat. Cell Biol. 6, 984–990.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Singh, S. M. , Murphy, B. , and O’Reilly, R. (2002). Epigenetic contributors to the discordance of monozygotic twins. Clin. Genet. 62, 97–103.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Strahl, B. D. , and Allis, C. D. (2000). The language of covalent histone modifications. Nature 403, 41–45.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Tamaru, H. , and Selker, E. U. (2001). A histone H3 methyltransferase controls DNA methylation in Neurospora crassa. Nature 414, 277–283.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Tate, P. , Skarnes, W. , and Bird, A. (1996). The methyl-CpG binding protein MeCP2 is essential for embryonic development in the mouse. Nat. Genet. 12, 205–208.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Tsujita, T. , Niikawa, N. , Yamashita, H. , Imamura, A. , Hamada, A. , Nakane, Y. , and Okazaki, Y. (1998). Genomic discordance between monozygotic twins discordant for schizophrenia. Am. J. Psychiatry 155, 422–424.
PubMed |

Veltman, M. W. , Thompson, R. J. , Roberts, S. E. , Thomas, N. S. , Whittington, J. , and Bolton, P. F. (2004). Prader–Willi syndrome: a study comparing deletion and uniparental disomy cases with reference to autism spectrum disorders. Eur. Child Adolesc. Psychiatry 13, 42–50.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Walsh, C. P. , Chaillet, J. R. , and Bestor, T. H. (1998). Transcription of IAP endogenous retroviruses is constrained by cytosine methylation. Nat. Genet. 20, 116–117.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Waterland, R. A. , and Jirtle, R. L. (2003). Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol. Cell. Biol. 23, 5293–5300.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Wilmut, I. , Schnieke, A. E. , McWhir, J. , Kind, A. J. , and Campbell, K. H. (1997). Viable offspring derived from fetal and adult mammalian cells. Nature 385, 810–813.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Wolff, G. L. , Kodell, R. L. , Moore, S. R. , and Cooney, C. A. (1998). Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice. FASEB J. 12, 949–957.
PubMed |

Yabuuchi, A. , Yasuda, Y. , Kato, Y. , and Tsunoda, Y. (2004). Effects of nuclear transfer procedures on ES cell cloning efficiency in the mouse. J. Reprod. Dev. 50, 263–268.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Yamagishi, H. , Ishii, C. , Maeda, J. , Kojima, Y. , Matsuoka, R. , Kimura, M. , Takao, A. , Momma, K. , and Matsuo, N. (1998). Phenotypic discordance in monozygotic twins with 22q11.2 deletion. Am. J. Med. Genet. 78, 319–321.
PubMed |

Young, L. E. , Sinclair, K. D. , and Wilmut, I. (1998). Large offspring syndrome in cattle and sheep. Rev. Reprod. 3, 155–163.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Young, L. E. , Fernandes, K. , McEvoy, T. G. , Butterwith, S. C. , Gutierrez, C. G. , Carolan, C. , Broadbent, P. J. , Robinson, J. J. , Wilmut, I. , and Sinclair, K. D. (2001). Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nat. Genet. 27, 153–154.
Crossref | GoogleScholarGoogle Scholar | PubMed |