Fig. 6. Sperm DNA damage induces heterogoneic and direct unequal cleavage divisions.

(A) Example karyogram of a seven-cell embryo (E122) produced with damaged sperm containing a segregation of uniparental maternal and paternal cells, suggesting a heterogoneic cell division of the zygote. Copy number changes are mostly present in the cells containing a paternal genome (C442, C443, C446, and C448), and cells with maternally inherited chromosomes are relatively unaffected by copy number changes, in contrast to the cells with paternally inherited chromosomes. (B) Embryos generated with damaged sperm contain more haploid and uniparental cells having a genomic content from either the father or the mother, indicating that sperm DNA damage causes heterogoneic cell divisions. Numbers above the bars indicate the number of analyzed cells per group. (C) In many embryos, only half of the cells are haploid/uniparental, suggesting that, in some cases, haploid/uniparental cells may arise after the two-cell stage. (D) Example of three haploid cells originating from a heterogoneic cell division at the zygote stage, which lead to segregation of the paternal and maternal genomes. Sister cells C47 and C48 contain a haploid maternal genome. The sister cell of C46 may have been lost during collection of the single blastomeres.