Chromosome errors in human eggs shape natural fertility over reproductive life span

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DOI

  • Jennifer R. Gruhn, Københavns Universitet
  • ,
  • Agata P. Zielinska, Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute)
  • ,
  • Vallari Shukla, Københavns Universitet
  • ,
  • Robert Blanshard, University of Sussex, Illumina Inc.
  • ,
  • Antonio Capalbo, Igenomix
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  • Danilo Cimadomo, G.en.e.r.a. Centers for Reproductive Medicine
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  • Dmitry Nikiforov, University of Copenhagen, University of Teramo
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  • Andrew Chi Ho Chan, Københavns Universitet
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  • Louise J. Newnham, University of Sussex
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  • Ivan Vogel, Københavns Universitet
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  • Catello Scarica, Sapienza University of Rome
  • ,
  • Marta Krapchev, INVICTA Fertility and Reproductive Center
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  • Deborah Taylor, University of Warwick
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  • Stine Gry Kristensen, University of Copenhagen
  • ,
  • Junping Cheng, University of Copenhagen
  • ,
  • Erik Ernst
  • Anne Mette Bay Bjørn
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  • Lotte Berdiin Colmorn, Rigshospitalet
  • ,
  • Martyn Blayney, Bourn Hall Clinic
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  • Kay Elder, Bourn Hall Clinic
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  • Joanna Liss, INVICTA Fertility and Reproductive Center, University of Gdansk
  • ,
  • Geraldine Hartshorne, University of Warwick
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  • Marie Louise Grøndahl, University of Copenhagen
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  • Laura Rienzi, G.en.e.r.a. Centers for Reproductive Medicine
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  • Filippo Ubaldi, G.en.e.r.a. Centers for Reproductive Medicine
  • ,
  • Rajiv McCoy, Johns Hopkins University
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  • Krzysztof Lukaszuk, INVICTA Fertility and Reproductive Center, Medical University of Gdansk, Medical University of Warsaw
  • ,
  • Claus Yding Andersen, Laboratory of Reproductive Biology, University of Copenhagen
  • ,
  • Melina Schuh, Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute)
  • ,
  • Eva R. Hoffmann, Københavns Universitet

Chromosome errors, or aneuploidy, affect an exceptionally high number of human conceptions, causing pregnancy loss and congenital disorders. Here, we have followed chromosome segregation in human oocytes from females aged 9 to 43 years and report that aneuploidy follows a U-curve. Specific segregation error types show different age dependencies, providing a quantitative explanation for the U-curve. Whole-chromosome nondisjunction events are preferentially associated with increased aneuploidy in young girls, whereas centromeric and more extensive cohesion loss limit fertility as women age. Our findings suggest that chromosomal errors originating in oocytes determine the curve of natural fertility in humans.

OriginalsprogEngelsk
TidsskriftScience
Vol/bind365
Nummer6460
Sider (fra-til)1466-1469
Antal sider4
ISSN0036-8075
DOI
StatusUdgivet - sep. 2019

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