Tripolar mitosis drives the association between maternal genotypes of PLK4 and aneuploidy in human preimplantation embryos

摘要: Aneuploidy is prevalent in human preimplantation embryos and the leading cause of pregnancy loss. Many aneuploidies arise during oogenesis, increasing frequency with maternal age. Superimposed on these meiotic are a range errors occurring early mitotic divisions embryo, contributing to widespread chromosomal mosaicism. Here we reanalyzed published dataset comprising genetic testing for aneuploidy 24,653 blastomere biopsies from day-3 cleavage-stage embryos, as well 17,051 trophectoderm day-5 blastocysts. We focused complex abnormalities that affected multiple chromosomes simultaneously, seeking quantify their incidences gain insight into mechanisms formation. In addition well-described patterns such triploidy haploidy, identified 4.7% blastomeres possessing karyotypes suggestive tripolar mitosis normally-fertilized diploid zygotes or descendant cells. further supported this hypothesis using time-lapse data an intersecting set 77 embryos. The signature was rare among blastocyst (0.5%), suggesting generated by impairs cellular and/or embryonic survival. Strikingly, found mechanism responsible previously described association common variants spanning PLK4. Our findings consistent role PLK4 master regulator centriole duplication known capacity induce when mutated mis-expressed. Taken together, propose key generating karyotype-wide implicate PLK4-mediated centrosome abnormality factor influencing its occurrence.