Sperm DNA damage causes genomic instability in early embryonic development

Sjors Middelkamp, Helena van Tol, Diana Spierings, Sander Boymans, Victor Guryev, Bernard Roelen, Peter Lansdorp, Edwin Cuppen, Ewart Kuijk

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Genomic instability is common in early embryo development, but the underlying causes are largely unknown. Here we examined the consequences of sperm DNA damage on the embryonic genome by single-cell genome sequencing of individual blastomeres from bovine embryos produced with sperm damaged by radiation. Sperm DNA damage caused fragmentation of chromosomes and segregation errors such as heterogoneic cell divisions yielding a broad spectrum of genomic aberrations that are similar to those frequently found in human embryos. The mosaic aneuploidies, mixoploidy, uniparental disomies and de novo structural variation induced upon sperm DNA damage may compromise health and lead to rare genomic disorders when embryos escape developmental arrest.One Sentence Summary DNA damage in sperm cells leads to genomic defects in embryos
Original languageEnglish
Article numbereaaz7602
Pages (from-to)1-12
Number of pages12
JournalScience advances
Volume6
Issue number16
DOIs
Publication statusPublished - 15 Apr 2020

Keywords

  • Biology
  • Chromosome
  • DNA damage
  • DNA sequencing
  • Embryo
  • Genetics
  • Genome
  • Genome instability
  • Sperm
  • Structural variation

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