ena-STUDY-Department of Human Genetics, KU Leuven-10-08-2021-20:02:55:673-1032
Multipolar zygotic divisions are characterized by parental genome segregation errors
The first mitotic division causes both parental genomes present in the zygote to segregate into two biparental diploid daughter cells. This fundamental tenet was challenged by the observation that blastomeres with different genome ploidy and distinct parental genotypes can coexist within individual embryos. We hypothesized that whole parental genomes can segregate into distinct blastomere lines during the multipolar division of the zygote, a phenomenon referred to as “heterogoneic” cell division. Here, we provide evidence of genome-wide segregation errors in two human blastocysts and further pinpoint its origin in a bovine model by mapping the genomic landscape of 82 blastomeres from 25 embryos that underwent multipolar division at the zygote stage using genome-wide SNP arrays and sequencing. In most embryos, the coexistence of androgenetic and diploid or polyploid blastomeres with or without anuclear blastomeres, androgenetic and anuclear blastomeres, and androgenetic and gynogenetic blastomeres within the same embryo provided proof that multipolar zygotic division coincides with heterogoneic segregation of the parental genome. By mapping the segregational origin of the genomic content, we deduced distinct segregation mechanisms underlying heterogoneic cell division including segregation by a tripolar spindle, the pronuclear extrusion of a paternal genome and, the operation of an ectopic paternal or private parental spindles. Polyspermic embryos expel excessive paternal genomes resulting in an androgenetic or polyploid blastomere. Confirming the results in human blastocysts, we found genome-wide segregation errors to persist in bovine blastocysts as well.
The first mitotic division causes both parental genomes present in the zygote to segregate into two biparental diploid daughter cells. This fundamental tenet was challenged by the observation that blastomeres with different genome ploidy and distinct parental genotypes can coexist within individual embryos. We hypothesized that whole parental genomes can segregate into distinct blastomere lines during the multipolar division of the zygote, a phenomenon referred to as “heterogoneic” cell division. Here, we provide evidence of genome-wide segregation errors in two human blastocysts and further pinpoint its origin in a bovine model by mapping the genomic landscape of 82 blastomeres from 25 embryos that underwent multipolar division at the zygote stage using genome-wide SNP arrays and sequencing. In most embryos, the coexistence of androgenetic and diploid or polyploid blastomeres with or without anuclear blastomeres, androgenetic and anuclear blastomeres, and androgenetic and gynogenetic blastomeres within the same embryo provided proof that multipolar zygotic division coincides with heterogoneic segregation of the parental genome. By mapping the segregational origin of the genomic content, we deduced distinct segregation mechanisms underlying heterogoneic cell division including segregation by a tripolar spindle, the pronuclear extrusion of a paternal genome and, the operation of an ectopic paternal or private parental spindles. Polyspermic embryos expel excessive paternal genomes resulting in an androgenetic or polyploid blastomere. Confirming the results in human blastocysts, we found genome-wide segregation errors to persist in bovine blastocysts as well.