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Science. 2019 Sep 27;365(6460):1466-1469. doi: 10.1126/science.aav7321.

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

Author information

1
DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
2
Max Planck Institute for Biophysical Chemistry, Department of Meiosis, Göttingen, Germany.
3
Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton, UK.
4
Illumina Inc., Fulbourn, UK.
5
Igenomix, Marostica, Italy.
6
G.en.e.r.a., Centers for Reproductive Medicine, Clinica Valle Giulia, via de notaris 2b, 00197 Rome, Italy.
7
Laboratory of Reproductive Biology, The Juliane Marie Centre for Women, Children and Reproduction, Copenhagen University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
8
Unit of Basic and Applied Biosciences, Università degli studi di Teramo, Teramo, Italy.
9
DAHFMO, Unit of Histology and Medical Embryology, Sapienza, University of Rome, Italy.
10
INVICTA Fertility and Reproductive Center, Gdańsk, Poland.
11
Warwick Medical School, University of Warwick and Centre for Reproductive Medicine, University Hospital Coventry, UK.
12
Department of Obstetrics and Gynaecology, University Hospital of Aarhus, Skejby Sygehus, Aarhus, Denmark.
13
The Fertility Clinic, The Juliane Marie Centre for Women, Children and Reproduction, Copenhagen University Rigshospitalet, Denmark.
14
Bourn Hall Clinic, Cambridge, UK.
15
Department of Biology and Medical Genetics, University of Gdańsk, Gdańsk, Poland.
16
Department of Obstetrics and Gynaecology, Department of Reproductive Medicine, Copenhagen University Hospital Herlev, Denmark.
17
Department of Biology, Johns Hopkins University, Baltimore, MD, USA.
18
Department of Obstetrics and Gynaecological Nursing, Faculty of Health Sciences, Medical University of Gdańsk, Gdańsk, Poland.
19
Department of Gynaecological Endocrinology, Medical University of Warsaw, Warsaw, Poland.
20
DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. eva@sund.ku.dk.
#
Contributed equally

Abstract

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.

PMID:
31604276
DOI:
10.1126/science.aav7321

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