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Human Genetics

, Volume 132, Issue 9, pp 1001–1013 | Cite as

The origin and impact of embryonic aneuploidy

  • Elpida FragouliEmail author
  • Samer Alfarawati
  • Katharina Spath
  • Souraya Jaroudi
  • Jonas Sarasa
  • Maria Enciso
  • Dagan Wells
Original Investigation

Abstract

Despite the clinical importance of aneuploidy, surprisingly little is known concerning its impact during the earliest stages of human development. This study aimed to shed light on the genesis, progression, and survival of different types of chromosome anomaly from the fertilized oocyte through the final stage of preimplantation development (blastocyst). 2,204 oocytes and embryos were examined using comprehensive cytogenetic methodology. A diverse array of chromosome abnormalities was detected, including many forms never recorded later in development. Advancing female age was associated with dramatic increase in aneuploidy rate and complex chromosomal abnormalities. Anaphase lag and congression failure were found to be important malsegregation causing mechanisms in oogenesis and during the first few mitotic divisions. All abnormalities appeared to be tolerated until activation of the embryonic genome, after which some forms started to decline in frequency. However, many aneuploidies continued to have little impact, with affected embryos successfully reaching the blastocyst stage. Results from the direct analyses of female meiotic divisions and early embryonic stages suggest that chromosome errors present during preimplantation development have origins that are more varied than those seen in later pregnancy, raising the intriguing possibility that the source of aneuploidy might modulate impact on embryo viability. The results of this study also narrow the window of time for selection against aneuploid embryos, indicating that most survive until the blastocyst stage and, since they are not detected in clinical pregnancies, must be lost around the time of implantation or shortly thereafter.

Keywords

Meiotic Division Blastocyst Stage Cleavage Stage Preimplantation Genetic Screening Preimplantation Development 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

Dagan Wells is supported by the NIHR Biomedical Research Centre Oxford.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Elpida Fragouli
    • 1
    • 2
    Email author
  • Samer Alfarawati
    • 2
  • Katharina Spath
    • 1
  • Souraya Jaroudi
    • 2
  • Jonas Sarasa
    • 2
  • Maria Enciso
    • 1
  • Dagan Wells
    • 1
    • 2
  1. 1.Nuffield Department of Obstetrics and GynaecologyUniversity of OxfordOxfordUK
  2. 2.Reprogenetics UKOxfordUK

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