Post‐metaphase correction of aberrant kinetochore‐microtubule attachments in mammalian eggs

Abstract

The accuracy of the two sequential meiotic divisions in oocytes is essential for creating a haploid gamete with a normal chromosomal content. Here, we have analysed the 3D dynamics of chromosomes during the second meiotic division in live mouse oocytes. We find that chromosomes form stable kinetochore–microtubule attachments at the end of prometaphase II stage that are retained until anaphase II onset. Remarkably, we observe that more than 20% of the kinetochore–microtubule attachments at the metaphase II stage are merotelic or lateral. However, < 1% of all chromosomes at onset of anaphase II are found to lag at the spindle equator and < 10% of the laggards missegregate and give rise to aneuploid gametes. Our results demonstrate that aberrant kinetochore–microtubule attachments are not corrected at the metaphase stage of the second meiotic division. Thus, the accuracy of the chromosome segregation process in mouse oocytes during meiosis II is ensured by an efficient correction process acting at the anaphase stage.

Ovulation suppression protects against chromosomal abnormalities in mouse eggs at advanced maternal age

“…To the extent that the mouse serves as an appropriate model for the maternal age effect, 19,21,[27][28][29]39,[75][76][77][78][79][80][81][82][83] our findings offer new perspectives on mammalian reproduction. 84 The data imply that ovulations are, directly or indirectly, a contributing cause to oocyte aging and the maternal age effect.…”

“…Unexpectedly, lagging chromosomes led to chromosomal abnormalities in only 47% of eggs (9/19 cells) (Figure 2E), suggesting that many lagging chromosomes eventually segregate properly and are captured on the meiosis II spindle; this is unlike in mitotically proliferating cells, where lagging chromosomes can form micronuclei. 39 Chromosome bridges resulted in chromosomal abnormalities in 6/7 cells, suggesting that these have a more detrimental effect (Figure 2E). Because the chromosome bridges were observed in oocytes from aged females, they were presumably not generated by meiotic recombination but through mechanisms occurring during aging.…”

Mechanisms underlying disruption of oocyte spindle stability by bisphenol compounds

“…Yet, analysis of kinetochore-MT attachments reveals fewer normal bioriented end-on attachments, and increased erroneous lateral MT attachments in BPF-exposed oocytes. Studies indicate that lateral chromosome-MT attachments are not resolved during MII-arrest in oocytes (Kouznetsova et al 2019) and do not satisfy the spindle assembly checkpoint (Kuhn & Dumont 2017). Longer exposure to either BPA or BPF conceivably exacerbates the incidence of erroneous chromosome-MT interactions and likely accounts for the significant chromosome misalignment and aneuploidy observed in oocytes exposed to bisphenols during meiotic maturation (Hunt et al 2003, Can et al 2005, Machtinger et al 2013.…”

CENP-V is required for proper chromosome segregation through interaction with spindle microtubules in mouse oocytes

“…Before fixation, oocytes were incubated in a cold buffer to preserve stable, kinetochore-attached microtubules (K-fibres), while the less stable, non-attached microtubules are lost. This treatment allows us to visualise specifically those K-fibres that are well attached to the chromosomes 38 , 39 . Because live imaging experiments (Figs.…”