Spindle dynamics and chromosome segregation in human preimplantation embryos

To investigate spindle dynamics and chromosome segregation in human preimplantation embryos. Chromosome segregation errors that cause aneuploidy are frequent in human preimplantation development. However, direct studies of the mechanisms of cell division in human embryos to understand the root causes of these errors are few.

Preimplantation human embryos were stained with SPY650-DNA and SPY555-tubulin to visualize mitotic chromosomes and microtubules, respectively, and spindle dynamics and chromosome segregation were analyzed using confocal live imaging.

Ninety-one cryopreserved embryos donated by 26 patients aged 24-41 years (mean age 34 years).

We used live imaging to analyze spindle assembly and chromosome segregation in human preimplantation embryos donated to research.

Mitosis duration, microtubule dynamics, and mitotic defects.

We find that spindle assembly occurs in an ‟outside-in" manner, followed by a canonical anaphase chromosome segregation, and a persistent spindle remnant that connects sister cells for several hours after anaphase. We find that chromosome segregation errors occur both at Day 2/3 and also in Day 5 embryos, including the generation of micronuclei that undergo a noncanonical inheritance pattern that is likely a major contributor to blastocyst aneuploidy.

Our data provide a foundational understanding of chromosome segregation mechanisms for further unravelling the causes of segregation error, and highlight micronuclei as a central player in aneuploidy genesis in human embryos.