Publication

Sperm DNA damage causes genomic instability in early embryonic development

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., Apr-2020, In : Science Advances. 6, 16, 12 p.

Research output: Contribution to journalArticleAcademicpeer-review

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 gamma-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.

Original languageEnglish
Number of pages12
JournalScience Advances
Volume6
Issue number16
Publication statusPublished - Apr-2020

    Keywords

  • CHROMOSOMAL MOSAICISM, PARENTAL GENOMES, READ ALIGNMENT, ORIGIN, FERTILIZATION, ANEUPLOIDY, CLEAVAGE, CONSEQUENCES, CHROMOTHRIPSIS, FRAGMENTATION

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