A major contributor to in vitro fertilization failure and embryo loss is aneuploidy. Human pre-implantation embryos often sequester mis-segregated chromosomes into micronuclei during mitosis, while undergoing a process called cellular fragmentation. Using live-cell imaging, single-cell/fragment DNA-Sequencing, and confocal analyses, we demonstrate in a large number of rhesus embryos that aneuploidy, micronuclei, and cellular fragmentation dynamics is conserved between primates. We also determined that ~18% of fragmented embryos encapsulate whole or partial chromosomes within cellular fragments, which are either maternal or paternal in origin and undergo DNA damage. Additional findings of reciprocal chromosome segments, uniparental genome segregation, and mixoploidy support the prevalence of chromosome breakage and abnormal cytokinesis. Despite frequent chromosomal errors, we show that embryos can prevent incorporation of fragments and non-dividing blastomeres at the blastocyst stage. We propose that embryos respond to segregation errors by eliminating micronuclei via cellular fragmentation and select against aneuploid blastomeres to overcome chromosome instability.. CC-BY-NC-ND 4.0 International license It is made available under a was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/241851 doi: bioRxiv preprint first posted online Jan. 2, 2018;
2The demand for human in vitro fertilization (IVF) increases each year, but success rates as measured by live birth(s) have remained only ~30-35% for decades (cdc.gov/art). One of the leading causes of IVF failure and embryo loss is the presence of unbalanced whole chromosome(s), or aneuploidy. Estimates of aneuploidy in IVF embryos via high-resolution techniques are 50-80%, including those from young, fertile couples and irrespective of stage [1][2][3][4][5][6] . Although difficult to ascertain, a similar efficiency (~30-35%) arises from natural human pregnancies, with up to 70% of spontaneous miscarriages diagnosed as aneuploid [7][8][9][10] . Chromosomal mis-segregation in oocytes during meiosis has long been considered the primary reason for aneuploidy, especially in cases of advanced maternal age. However, recent studies using comprehensive chromosome screening (CCS) of all blastomeres in cleavage-stage human embryos established that mitotic errors occur at an equal or greater frequency than meiotic errors and irrespective of maternal age 1,2,4,6,11,12 . Mitotic chromosome mis-segregation may not only lead to aneuploidy, but can also give rise to a mosaic embryo with different chromosomal copy number amongst cells. While classified as aneuploid, euploid-aneuploid mosaic embryos may still result in the birth of healthy offspring upon transfer, which suggests that corrective mechanisms exist to overcome chromosomal instability (CIN) during pre-implantation development [13][14][15] .Another determining factor for the capacity...