Observation of two separate bipolar spindles in the human zygote

Xu, Xiaoming; Li, Linheng; Zhang, Chuilian; Li, Meng

doi:10.1007/s10815-019-01440-x

Cited by 11 publications

(7 citation statements)

References 6 publications

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“…This distinctive spindle formation distinguishes mitosis I from the later mitoses and could explain why it is so error-prone (the two spindles not fusing together properly could cause multipolar spindles and an increased prevalence of merotelic attachments). A dual spindle has also been reported in a human zygote (Xu et al, 2019). We were able to observe the formation of a dual spindle in a 3PN embryo (Fig.…”

Section: Results-and-discussionsupporting

confidence: 84%

The First Mitotic Division of the Human Embryo is Highly Error-prone

Ford

Currie

Taylor

et al. 2020

Preprint

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Aneuploidy in human embryos is surprisingly prevalent and increases drastically with maternal age, resulting in miscarriages, infertility and birth defects. Frequent errors during the meiotic divisions cause this aneuploidy, while age-independent errors during the first cleavage divisions of the embryo also contribute. However, the underlying mechanisms are poorly understood, largely because these events have never been visualised in living human embryos. Here, using cell-permeable DNA dyes, we film chromosome segregation during the first and second mitotic cleavage divisions in human embryos from women undergoing assisted reproduction following ovarian stimulation. We show that the first mitotic division takes several hours to complete and is highly variable. Timings of key mitotic events were, however, largely consistent with clinical videos of embryos that gave rise to live births. Multipolar divisions and lagging chromosomes during anaphase were frequent with no maternal age association. In contrast, the second mitosis was shorter and underwent mostly bipolar divisions with no detectable lagging chromosomes. We propose that the first mitotic division in humans is a unique and highly error-prone event, which contributes to fetal aneuploidies.

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Section: Results-and-discussionsupporting

confidence: 84%

The First Mitotic Division of the Human Embryo is Highly Error-prone

Ford

Currie

Taylor

et al. 2020

Preprint

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“…30 This dual spindle formation is unlike what has been reported in literature so far, in which the sperm only is believed to deliver the zygotic spindle. Interestingly, Xu et al 31 recently observed a dual spindle in human embryos. Furthermore, genotyping of monochorionic twins indirectly implicated heterogoneic division in the etiology of sesquizygotic twinning chimeras.…”

Section: Heterogoneic Cell Divisionmentioning

confidence: 99%

“…The concept of spindle apposition is guided by recent findings of two separate spindle formations in zygotes. 30,31 Maternal chromosomes are colored in shades of pink, while paternal chromosomes are in shades of blue. In normal fertilization, one haploid female genome will fuse with a haploid male genome and the zygote will create two diploid biparental blastomeres.…”

Section: Triploidymentioning

confidence: 99%

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Genome‐wide abnormalities in embryos: Origins and clinical consequences

2021

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Ploidy or genome‐wide chromosomal anomalies such as triploidy, diploid/triploid mixoploidy, chimerism, and genome‐wide uniparental disomy are the cause of molar pregnancies, embryonic lethality, and developmental disorders. While triploidy and genome‐wide uniparental disomy can be ascribed to fertilization or meiotic errors, the mechanisms causing mixoploidy and chimerism remain shrouded in mystery. Different models have been proposed, but all remain hypothetical and controversial, are deduced from the developmental persistent genomic constitutions present in the sample studied and lack direct evidence. New single‐cell genomic methodologies, such as single‐cell genome‐wide haplotyping, provide an extended view of the constitution of normal and abnormal embryos and have further pinpointed the existence of mixoploidy in cleavage‐stage embryos. Based on those recent findings, we suggest that genome‐wide anomalies, which persist in fetuses and patients, can for a large majority be explained by a noncanonical first zygotic cleavage event, during which maternal and paternal genomes in a single zygote, segregate to different blastomeres. This process, termed heterogoneic division, provides an overarching theoretical basis for the different presentations of mixoploidy and chimerism.

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“…Recently, an elegant microscopy study in mice demonstrated that male and female chromosomes are assembled on separate mitotic spindles during the first zygotic division, questioning the textbook concept of syngamy (Reichmann et al 2018). Intriguingly, dual spindle formation also seems to exist in humans (Xu et al 2019). Hence, failure to properly align two zygotic spindles may potentially provide a mechanistic basis for heterogoneic division and mixoploidy in embryos.…”

Section: Heterogoneic Cell Divisionmentioning

confidence: 99%

PREIMPLANTATION GENETIC TESTING: Single-cell technologies at the forefront of PGT and embryo research

et al. 2020

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While chromosomal mosaicism in the embryo was observed already in the ‘90s using both karyotyping and FISH technologies, the full extent of this phenomenon and the overall awareness of the consequences of chromosomal instability on embryo development has only come with the advent of sophisticated single-cell technologies. High-throughput techniques, such as DNA microarrays and massive parallel sequencing, have shifted single-cell genome research from evaluating a few loci at a time to the ability to perform comprehensive screening of all 24 chromosomes. The development of genome-wide single-cell haplotyping methods have also enabled for simultaneous detection of single-gene disorders and aneuploidy using a single universal protocol. Today, three decades later haplotyping-based embryo testing is performed worldwide to reliably detect virtually any Mendelian hereditary disease with a known cause, including autosomal-recessive, autosomal-dominant and X-linked disorders. At the same time, these single-cell assays have also provided unique insight into the complexity of embryo genome dynamics, by elucidating mechanistic origin, nature and developmental fate of embryonic aneuploidy. Understanding the impact of post-zygotically acquired genomic aberrations on embryo development is essential to determine the still controversial diagnostic value of aneuploidy screening. For that reason, considerable efforts have been put into linking the genetic constitution of the embryo not only to its morphology and implantation potential, but more importantly to its transcriptome using single-cell RNA sequencing. Collectively, these breakthrough technologies have revolutionized single-cell research and clinical practice in assisted reproduction and led to unique discoveries in early embryogenesis.

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Observation of two separate bipolar spindles in the human zygote

Cited by 11 publications

References 6 publications

The First Mitotic Division of the Human Embryo is Highly Error-prone

The First Mitotic Division of the Human Embryo is Highly Error-prone

Genome‐wide abnormalities in embryos: Origins and clinical consequences

PREIMPLANTATION GENETIC TESTING: Single-cell technologies at the forefront of PGT and embryo research

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