4.7 Article

Age-dependent aneuploidy in mammalian oocytes instigated at the second meiotic division

Journal

AGING CELL
Volume 21, Issue 7, Pages -

Publisher

WILEY
DOI: 10.1111/acel.13649

Keywords

age-dependent aneuploidy; chromosome; meiosis; oocyte; second meiotic division; segregation

Funding

  1. Cancerfonden [170226]
  2. Horizon 2020 Framework Programme [634113]
  3. Karolinska Institutet
  4. Vetenskapsradet [K2013-54X-21397-04-S]
  5. National Microscopy Infrastructure [VR-RFI-2019-00217]
  6. H2020 Societal Challenges Programme [634113] Funding Source: H2020 Societal Challenges Programme

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Aging significantly impacts the chromosome segregation process in human oocytes, leading to aneuploidy, infertility, and developmental disorders. As age increases, the likelihood of chromosome segregation irregularities also increases, resulting in a higher incidence of aneuploidy.
Ageing severely affects the chromosome segregation process in human oocytes resulting in aneuploidy, infertility and developmental disorders. A considerable amount of segregation errors in humans are introduced at the second meiotic division. We have here compared the chromosome segregation process in young adult and aged female mice during the second meiotic division. More than half of the oocytes in aged mice displayed chromosome segregation irregularities at anaphase II, resulting in dramatically increased level of aneuploidy in haploid gametes, from 4% in young adult mice to 30% in aged mice. We find that the post-metaphase II process that efficiently corrects aberrant kinetochore-microtubule attachments in oocytes in young adult mice is approximately 10-fold less efficient in aged mice, in particular affecting chromosomes that show small inter-centromere distances at the metaphase II stage in aged mice. Our results reveal that post-metaphase II processes have critical impact on age-dependent aneuploidy in mammalian eggs.

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