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Sperm DNA damage causes genomic instability in early embryonic development.
Sci Adv. 2020 Apr; 6(16):eaaz7602.SA

Abstract

Genomic instability is common in human embryos, but the underlying causes are largely unknown. Here, we examined the consequences of sperm DNA damage on the embryonic genome by single-cell whole-genome sequencing of individual blastomeres from bovine embryos produced with sperm damaged by γ-radiation. Sperm DNA damage primarily leads to fragmentation of the paternal chromosomes followed by random distribution of the chromosomal fragments over the two sister cells in the first cell division. An unexpected secondary effect of sperm DNA damage is the induction of direct unequal cleavages, which include the poorly understood heterogoneic cell divisions. As a result, chaotic mosaicism is common in embryos derived from fertilizations with damaged sperm. The mosaic aneuploidies, uniparental disomies, and de novo structural variation induced by sperm DNA damage may compromise fertility and lead to rare congenital disorders when embryos escape developmental arrest.

Authors+Show Affiliations

Center for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, Utrecht 3584 CG, Netherlands.Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, Utrecht 3584 CM, Netherlands.European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen 9713 AV, Netherlands.Center for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, Utrecht 3584 CG, Netherlands.European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen 9713 AV, Netherlands.Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, Utrecht 3584 CM, Netherlands.European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen 9713 AV, Netherlands. Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada. Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.Center for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, Utrecht 3584 CG, Netherlands. Hartwig Medical Foundation, Amsterdam, Netherlands.Center for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, Utrecht 3584 CG, Netherlands.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32494621

Citation

Middelkamp, Sjors, et al. "Sperm DNA Damage Causes Genomic Instability in Early Embryonic Development." Science Advances, vol. 6, no. 16, 2020, pp. eaaz7602.
Middelkamp S, van Tol HTA, Spierings DCJ, et al. Sperm DNA damage causes genomic instability in early embryonic development. Sci Adv. 2020;6(16):eaaz7602.
Middelkamp, S., van Tol, H. T. A., Spierings, D. C. J., Boymans, S., Guryev, V., Roelen, B. A. J., Lansdorp, P. M., Cuppen, E., & Kuijk, E. W. (2020). Sperm DNA damage causes genomic instability in early embryonic development. Science Advances, 6(16), eaaz7602. https://doi.org/10.1126/sciadv.aaz7602
Middelkamp S, et al. Sperm DNA Damage Causes Genomic Instability in Early Embryonic Development. Sci Adv. 2020;6(16):eaaz7602. PubMed PMID: 32494621.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sperm DNA damage causes genomic instability in early embryonic development. AU - Middelkamp,Sjors, AU - van Tol,Helena T A, AU - Spierings,Diana C J, AU - Boymans,Sander, AU - Guryev,Victor, AU - Roelen,Bernard A J, AU - Lansdorp,Peter M, AU - Cuppen,Edwin, AU - Kuijk,Ewart W, Y1 - 2020/04/15/ PY - 2019/10/07/received PY - 2020/01/22/accepted PY - 2020/6/5/entrez PY - 2020/6/5/pubmed PY - 2020/6/5/medline SP - eaaz7602 EP - eaaz7602 JF - Science advances JO - Sci Adv VL - 6 IS - 16 N2 - Genomic instability is common in human embryos, but the underlying causes are largely unknown. Here, we examined the consequences of sperm DNA damage on the embryonic genome by single-cell whole-genome sequencing of individual blastomeres from bovine embryos produced with sperm damaged by γ-radiation. Sperm DNA damage primarily leads to fragmentation of the paternal chromosomes followed by random distribution of the chromosomal fragments over the two sister cells in the first cell division. An unexpected secondary effect of sperm DNA damage is the induction of direct unequal cleavages, which include the poorly understood heterogoneic cell divisions. As a result, chaotic mosaicism is common in embryos derived from fertilizations with damaged sperm. The mosaic aneuploidies, uniparental disomies, and de novo structural variation induced by sperm DNA damage may compromise fertility and lead to rare congenital disorders when embryos escape developmental arrest. SN - 2375-2548 UR - https://www.unboundmedicine.com/medline/citation/32494621/Sperm_DNA_damage_causes_genomic_instability_in_early_embryonic_development L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/32494621/ DB - PRIME DP - Unbound Medicine ER -
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