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REVIEW
Contents Vol 16(3)

Society for Reproductive Biology Founders’ Lecture 2003. The making of an embryo: short-term goals and long-term implications

Tom P. Fleming A B , Adrian Wilkins A , Andrew Mears A , Daniel J. Miller A , Fay Thomas A , M. Reza Ghassemifar A , Irina Fesenko A , Bhavwanti Sheth A , Wing Yee Kwong A and Judith J. Eckert A
+ Author Affiliations
- Author Affiliations

A Division of Cell Sciences, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK.

B To whom correspondence should be addressed. email: tpf@soton.ac.uk

Reproduction, Fertility and Development 16(3) 1-13 https://doi.org/10.1071/RD03070
Submitted: 29 September 2003  Accepted: 11 February 2004   Published: 30 April 2004

Abstract

During early development, the eutherian mammalian embryo forms a blastocyst comprising an outer trophectoderm epithelium and enclosed inner cell mass (ICM). The short-term goal of blastocyst morphogenesis, including epithelial differentiation and segregation of the ICM, is mainly regulated autonomously and comprises a combination of temporally controlled gene expression, cell polarisation, differentiative cell divisions and cell–cell interactions. This aspect of blastocyst biogenesis is reviewed, focusing, in particular, on the maturation and role of cell adhesion systems. Early embryos are also sensitive to their environment, which can affect their developmental potential in diverse ways and may lead to long-term consequences relating to fetal or postnatal growth and physiology. Some current concepts of embryo–environment interactions, which may impact on future health, are also reviewed.

Extra keywords: blastocyst, cell adhesion, compaction, environmental factors, fetal programming, inner cell mass, systolic blood pressure, tight junctions, trophectoderm.


Acknowledgments

We are grateful to the Medical Research Council and the Wellcome Trust for financial support of research within the laboratory of T. P. F.


References

Amleh, A. , and Dean, J. (2002). Mouse genetics provides insight into folliculogenesis, fertilization and early embryonic development.  Hum. Reprod. Update 8, 395–403.
| PubMed | Barker D. J. P. (1998). ‘Mothers, Babies and Health in Later Life’, 2nd edn. (Churchill Livingstone: Edinburgh, UK.)

Barker, D. J. P. , Osmond, C. , Rodin, I. , Fall, C. H. D. , and Winter, P. D. (1995). Low weight gain in infancy and suicide in adult life. BMJ 311, 1203.
| PubMed | Butler S. (1912). ‘The Note-Books of Samuel Butler.’ (A. C. Fifield: London, UK.)

Campbell, S. , Swann, H. R. , Seif, M. W. , Kimber, S. J. , and Aplin, J. D. (1995). Cell adhesion molecules on the oocyte and preimplantation human embryo. Hum. Reprod. 10, 1571–1578.
| PubMed | Leese H. J. , and Isherwood-Peel G. (1999). Early embryo nutrition and disorders in later life. In ‘Fetal Programming: Influences on Development and Disease in Later Life’. (Eds P. M. S. O’Brien, T. Wheeler and D. J. P. Barker.) pp. 104–116. (RCOG Press: London, UK.)

Levine, R. S. , Hennekens, C. H. , and Jesse, M. J. (1994). Blood pressure in prospective population based cohort of newborn and infant twins. BMJ 308, 298–302.
| PubMed |

Levy, J. , Johnson, M. H. , Goodall, H. , and Maro, B. (1986). The timing of compaction: control of a major developmental transition in mouse early morphogenesis. J. Embryol. Exp. Morphol. 95, 213–237.
| PubMed |

Lighten, A. D. , Moore, G. E. , Winston, R. M. , and Hardy, K. (1998). Routine addition of human insulin-like growth factor-I ligand could benefit clinical in-vitro fertilization culture. Hum. Reprod. 13, 3144–3150.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Louvet, S. , Aghion, J. , Santa-Maria, A. , Mangeat, P. , and Maro, B. (1996). Ezrin becomes restricted to outer cells following asymmetrical division in the preimplantation mouse embryo. Dev. Biol. 177, 568–579.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

MacPhee, D. J. , Jones, D. H. , Barr, K. J. , Betts, D. H. , Watson, A. J. , and Kidder, G. M. (2000). Differential involvement of Na(+),K(+)-ATPase isozymes in preimplantation development of the mouse. Dev. Biol. 222, 486–498.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Maro, B. , Johnson, M. H. , Pickering, S. J. , and Louvard, D. (1985). Changes in the distribution of membranous organelles during mouse early development. J. Embryol. Exp. Morphol. 90, 287–309.
| PubMed |

Martin, P. M. , and Sutherland, A. E. (2001). Exogenous amino acids regulate trophectoderm differentiation in the mouse blastocyst through an mTOR-dependent pathway. Dev. Biol. 240, 182–193.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Miller, D. J. , Eckert, J. J. , Lazzari, G. , Durathon-Richoux, V. , Sreenan, J. , Morris, D. , Galli, C. , Renard, J.-P. , and Fleming, T. P. (2003). Tight junction mRNA expression levels in bovine embryos are dependent upon the ability to compact and in vitro culture methods. Biol. Reprod. 68, 1394–1402.
| PubMed |

Mitalipov, S. M. , Kuo, H.-C. , Hennebold, J. D. , and Wolf, D. P. (2003). Oct-4 expression in pluripotent cells of the rhesus monkey. Biol. Reprod. 69, 1785–1792.
| PubMed |

Natale, D. R. , and Watson, A. J. (2002). Rac-1 and IQGAP are potential regulators of E-cadherin-catenin interactions during murine preimplantation development. Gene Expr. Patterns 2, 17–22.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Nichols, J. , Zevnik, B. , Anastassiadis, K. , Niwa, H. , Klewe-Nebenius, D. , Chambers, I. , Scholer, H. , and Smith, A. (1998). Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell 95, 379–391.
| 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 |

Nikas, G. , Ao, A. , Winston, R. M. , and Handyside, A. H. (1996). Compaction and surface polarity in the human embryo in vitro. Biol. Reprod. 55, 32–37.
| PubMed |

Offenberg, H. , Barcroft, L. C. , Caveney, A. , Viuff, D. , Thomsen, P. D. , and Watson, A. J. (2000). mRNAs encoding aquaporins are present during murine preimplantation development. Mol. Reprod. Dev. 57, 323–330.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Ohno, M. , Aoki, N. , and Sasaki, H. (2001). Allele-specific detection of nascent transcripts by fluorescence in situ hybridization reveals temporal and culture-induced changes in Igf2 imprinting during pre-implantation mouse development. Genes Cells 6, 249–259.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Ohsugi, M. , Hwang, S. Y. , Butz, S. , Knowles, B. B. , Solter, D. , and Kemler, R. (1996). Expression and cell membrane localization of catenins during mouse preimplantation development. Dev. Dyn. 206, 391–402.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Ohsugi, M. , Butz, S. , and Kemler, R. (1999). Beta-catenin is a major tyrosine-phosphorylated protein during mouse oocyte maturation and preimplantation development. Dev. Dyn. 216, 168–176.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

O’Regan, D. , Welberg, L. L. A. M. , Holmes, M. C. , and Seckl, J. R. (2001). Glucocorticoid programming of pituitary–adrenal function: mechanisms and physiological consequences. Semin. Neonatol. 6, 319–329.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Pauken, C. M. , and Capco, D. G. (1999). Regulation of cell adhesion during embryonic compaction of mammalian embryos: roles for PKC and beta-catenin. Mol. Reprod. Dev. 54, 135–144.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Pesce, M. , and Scholer, H. R. (2001). Oct-4: gatekeeper in the beginnings of mammalian development. Stem Cells 19, 271–278.
| PubMed |

Petrie, L. , Duthie, S. J. , Rees, W. D. , and McConnell, J. M. L. (2002). Serum concentrations of homocysteine are elevated during early pregnancy in rodent models of fetal programming. Br. J. Nutr. 88, 471–477.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Pey, R. , Vial, C. , Schatten, G. , and Hafner, M. (1998). Increase in intracellular Ca2+ and relocation of E-cadherin during experimental decompaction of mouse embryos. Proc. Natl Acad. Sci. USA 95, 12 977–12 982.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Pickering, S. J. , Maro, B. , Johnson, M. H. , and Skepper, J. N. (1988). The influence of cell contact on the division of mouse 8-cell blastomeres. Development 103, 353–363.
| PubMed |

Power, M. A. , and Tam, P. P. L. (1993). Onset of gastrulation, morphogenesis and somitogenesis in mouse embryos displaying compensatory growth. Anat. Embryol. 187, 493–504.
| PubMed |

Ratnam, S. , Mertineit, C. , Ding, F. , Howell, C. Y. , Clarke, H. J. , Bestor, T. H. , Chaillet, J. R. , and Trasler, J. M. (2002). Dynamics of Dnmt1 methyltransferase expression and intracellular localization during oogenesis and preimplantation development. Dev. Biol. 245, 304–314.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Reeve, W. J. D. (1981). Cytoplasmic polarity develops at compaction in rat and mouse embryos. J. Embryol. Exp. Morphol. 62, 351–367.
| PubMed |

Reik, W. , Dean, W. , and Walter, J. (2001). Epigenetic reprogramming in mammalian development. Science 293, 1089–1093.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Reima, I. , Lehtonen, E. , Virtanen, I. , and Flechon, J. E. (1993). The cytoskeleton and associated proteins during cleavage, compaction and blastocyst differentiation in the pig. Differentiation 54, 35–45.
| 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 |

Riethmacher, D. , Brinkmann, V. , and Birchmeier, C. (1995). A targeted mutation in the mouse E-cadherin gene results in defective preimplantation development. Proc. Natl Acad. Sci. USA 92, 855–859.
| PubMed |

Robson, P. , Stein, P. , Zhou, B. , Schultz, R. M. , and Baldwin, H. S. (2001). Inner cell mass-specific expression of a cell adhesion molecule (PECAM-1/CD31) in the mouse blastocyst. Dev. Biol. 234, 317–329.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Rossant, J. , Chazaud, C. , and Yamanaka, Y. (2003). Lineage allocation and asymmetries in the early mouse embryo. Philos. Trans. R. Soc. Lond. B Biol. Sci. 358, 1341–1349.
| 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 |

Schieve, L. A. , Meikle, S. F. , Ferre, C. , Peterson, H. B. , Jeng, G. , and Wilcox, L. S. (2002). Low and very low birth weight in infants conceived with use of assisted reproductive technology. N. Engl. J. Med. 346, 731–737.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Schultz, R. M. (2002). The molecular foundations of the maternal to zygotic transition in the preimplantation embryo. Hum. Reprod. Update 8, 323–331.
| PubMed |

Sefton, M. , Johnson, M. H. , and Clayton, L. (1992). Synthesis and phosphorylation of uvomorulin during mouse early development. Development 115, 313–318.
| PubMed |

Sefton, M. , Johnson, M. H. , Clayton, L. , and McConnell, J. M. (1996). Experimental manipulations of compaction and their effects on the phosphorylation of uvomorulin. Mol. Reprod. Dev. 44, 77–87.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Sheth, B. , Fesenko, I. , Collins, J. E. , Moran, B. , Wild, A. E. , Anderson, J. M. , and Fleming, T. P. (1997). Tight junction assembly during mouse blastocyst formation is regulated by late expression of ZO-1α+ isoform. Development 124, 2027–2037.
| PubMed |

Sheth, B. , Fontaine, J.-J. , Ponza, E. , McCallum, A. , Page, A. , Zahraoui, A. , Citi, S. , Louvard, D. , and Fleming, T. P. (2000). Differentiation of the epithelial apical junctional complex during mouse preimplantation development: a role for rab13 in the early maturation of the tight junction. Mech. Dev. 97, 93–104.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Sheth, B. , Moran, B. , Anderson, J. M. , and Fleming, T. P. (2000). Post-translational control of occludin membrane assembly in mouse trophectoderm: a mechanism to regulate timing of tight junction biogenesis and blastocyst formation. Development 127, 831–840.
| PubMed |

Sinclair, K. D. , Young, L. E. , Wilmut, I. , and McEvoy, T. G. (2000). In-utero overgrowth in ruminants following embryo culture: lessons from mice and a warning to men. Hum. Reprod. 15, 68–86.Suppl 5
| PubMed |

Spanos, S. , Becker, D. L. , Winston, R. M. , and Hardy, K. (2000). Anti-apoptotic action of insulin-like growth factor-I during human preimplantation embryo development. Biol. Reprod. 63, 1413–1420.
| PubMed |

Stojanov, T. , and O’Neill, C. (2001). In vitro fertilization causes epigenetic modifications to the onset of gene expression from the zygotic genome in mice. Biol. Reprod. 64, 696–705.
| PubMed |

Stojanov, T. , Alechna, S. , and O’Neill, C. (1999). In vitro fertilization and culture of mouse embryos in vitro significantly retards the onset of insulin-like growth factor-II expression from the zygotic genome. Mol. Hum. Reprod. 5, 116–124.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Surani, M. A. , and Barton, S. C. (1984). Spatial distribution of blastomeres is dependent on cell division order and interactions in mouse morulae. Dev. Biol. 102, 335–343.
| PubMed |

Talbot, P. , Shur, B. D. , and Myles, D. G. (2003). Cell adhesion and fertilization: steps in oocyte transport, sperm–zona pellucida interactions, and sperm–egg fusion. Biol. Reprod. 68, 1–9.
| PubMed |

Tam, P. P. L. (1988). Postimplantation development of mitomycin-C treated mouse blastocysts. Teratology 37, 205–212.
| PubMed |

Tarlatzis, B. C. , and Grimbizis, G. (1999). Pregnancy and child outcome after assisted reproduction techniques. Hum. Reprod. 14, 231–242.Suppl. 1
| PubMed |

Tesarik, J. , and Mendoza, C. (1999). In vitro fertilization by intracytoplasmic sperm injection. Bioessays 21, 791–801.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Thompson, J. G. , Kind, K. L. , Roberts, C. T. , Robertson, S. A. , and Robinson, J. S. (2002). Epigenetic risks related to assisted reproductive technologies: short- and long-term consequences for the health of children conceived through assisted reproduction technology: more reason for caution? Hum. Reprod. 17, 2783–2786.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Torres, M. , Stoykova, A. , Huber, O. , Chowdhury, K. , Bonaldo, P. , Mansouri, A. , Butz, S. , Kemler, R. , and Gruss, P. (1997). An alpha-E-catenin gene trap mutation defines its function in preimplantation development. Proc. Natl Acad. Sci. USA 94, 901–906.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Turner, K. , Martin, K. L. , Woodward, B. J. , Lenton, E. A. , and Leese, H. J. (1994). Comparison of pyruvate uptake by embryos derived from conception and non-conception natural cycles. Hum. Reprod. 9, 2362–2366.
| PubMed |

Vance, M. M. , and Wiley, L. M. (1999). Gap junction intercellular communication mediates the competitive cell proliferation disadvantage of irradiated mouse preimplantation embryos in aggregation chimeras. Radiat. Res. 152, 544–551.
| PubMed |

van der Lende, T. , de Loos, F. A. , and Jorna, T. (2000). Postnatal health and welfare of offspring conceived in vitro: a case for epidemiological studies. Theriogenology 53, 549–554.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Van Soom, A. , Boerjan, M. L. , Bols, P. E. , Vanroose, G. , Lein, A. , Coryn, M. , and de Kruif, A. (1997). Timing of compaction and inner cell allocation in bovine embryos produced in vivo after superovulation. Biol. Reprod. 57, 1041–1049.
| PubMed |

Vestweber, D. , Gossler, A. , Boller, K. , and Kemler, R. (1987). Expression and distribution of cell adhesion molecule uvomorulin in mouse preimplantation embryos. Dev. Biol. 124, 451–456.
| PubMed |

Wassarman, P. M. (2002). Sperm receptors and fertilization in mammals. Mt Sinai J. Med. 69, 148–155.
| PubMed |

Watson, A. J. , and Barcroft, L. C. (2001). Regulation of blastocyst formation. Front. Biosci. 6, 708–730.


Wiemer, K. E. , Cohen, J. , Tucker, M. J. , and Godke, R. A. (1998). The application of co-culture in assisted reproduction: 10 years of experience with human embryos. Hum. Reprod. 13, 226–238.Suppl. 4
| PubMed |

Winkel, G. K. , Ferguson, J. E. , Takeichi, M. , and Nuccitelli, R. (1990). Activation of protein kinase C triggers premature compaction in the four-cell stage mouse embryo. Dev. Biol. 138, 1–15.
| PubMed |

Winston, R. M. , and Hardy, K. (2002). Are we ignoring potential dangers of in vitro fertilization and related treatments? Nat. Cell Biol. 4, S14–S18.Suppl.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Wrenzycki, C. , Herrmann, D. , Carnwath, J. W. , and Niemann, H. (1996). Expression of the gap junction gene connexin43 (Cx43) in preimplantation bovine embryos derived in vitro or in vivo. J. Reprod. Fertil. 108, 17–24.
| PubMed |

Young, L. E. , and Fairburn, H. R. (2000). Improving the safety of embryo technologies: possible role of genomic imprinting. Theriogenology 53, 627–648.
| 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. (2001). Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nat. Genet. 27, 153–154.
| Crossref | GoogleScholarGoogle Scholar | PubMed |

Zernicka-Goetz, M. (2002). Patterning of the embryo: the first spatial decisions in the life of a mouse. Development 129, 815–829.
| PubMed |

Ziomek, C. A. , and Johnson, M. H. (1980). Cell surface interactions induce polarisation of mouse 8-cell blastomeres at compaction. Cell 21, 935–942.
| PubMed |