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Sperm DNA damage causes genomic instability in early embryonic development.


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.

SUBMITTER: Middelkamp S 

PROVIDER: S-EPMC7159919 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Sperm DNA damage causes genomic instability in early embryonic development.

Middelkamp Sjors S   van Tol Helena T A HTA   Spierings Diana C J DCJ   Boymans Sander S   Guryev Victor V   Roelen Bernard A J BAJ   Lansdorp Peter M PM   Cuppen Edwin E   Kuijk Ewart W EW  

Science advances 20200415 16


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 u  ...[more]

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