ena-STUDY-UNIVERSITY MEDICAL CENTER UTRECHT-22-05-2019-12:08:45:102-391
Sperm DNA damage causes genomic instability in early embryonic development
The majority of human embryos are lost early in development due to genetic mosaicism that affects about 75% of the human embryos. In spite of the impact on human health and fecundity, the factors that underlie this embryonic genome instability 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 two- and eight-cell embryos produced with sperm damaged by radiation. Sperm DNA damage was found to induce a broad spectrum of genomic aberrations through fragmentation of chromosomes in two-cell stage embryos and the induction of segregation errors and heterogoneic cell divisions. Embryos that manage to escape developmental arrest may compromise health by causing mosaic aneuploidies, mixoploidy, uniparental disomies, de novo structural variation and possibly other rare genomic disorders of early embryonic origin.
The majority of human embryos are lost early in development due to genetic mosaicism that affects about 75% of the human embryos. In spite of the impact on human health and fecundity, the factors that underlie this embryonic genome instability 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 two- and eight-cell embryos produced with sperm damaged by radiation. Sperm DNA damage was found to induce a broad spectrum of genomic aberrations through fragmentation of chromosomes in two-cell stage embryos and the induction of segregation errors and heterogoneic cell divisions. Embryos that manage to escape developmental arrest may compromise health by causing mosaic aneuploidies, mixoploidy, uniparental disomies, de novo structural variation and possibly other rare genomic disorders of early embryonic origin.