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Updated: Mar 1, 2026
Using Mouse Oocytes to Assess Human Gene Function During Meiosis I
Published on: April 10, 2018
Merotelic kinetochore attachment in oocyte meiosis II causes sister chromatids segregation errors in aged mice
Jin-Mei Cheng1,2,3, Jian Li1,2, Ji-Xin Tang1,2
1a State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology , Chinese Academy of Sciences , Beijing , China.
Abstract:
Mammalian oocyte chromosomes undergo 2 meiotic divisions to generate haploid gametes. The frequency of chromosome segregation errors during meiosis I increase with age. However, little attention has been paid to the question of how aging affects sister chromatid segregation during oocyte meiosis II. More importantly, how aneuploid metaphase II (MII) oocytes from aged mice evade the spindle assembly checkpoint (SAC) mechanism to complete later meiosis II to form aneuploid embryos remains unknown. Here, we report that MII oocytes from naturally aged mice exhibited substantial errors in chromosome arrangement and configuration compared with young MII oocytes. Interestingly, these errors in aged oocytes had no impact on anaphase II onset and completion as well as 2-cell formation after parthenogenetic activation. Further study found that merotelic kinetochore attachment occurred more frequently and could stabilize the kinetochore-microtubule interaction to ensure SAC inactivation and anaphase II onset in aged MII oocytes. This orientation could persist largely during anaphase II in aged oocytes, leading to severe chromosome lagging and trailing as well as delay of anaphase II completion. Therefore, merotelic kinetochore attachment in oocyte meiosis II exacerbates age-related genetic instability and is a key source of age-dependent embryo aneuploidy and dysplasia.
Insights
Aging impairs oocyte meiosis II, leading to chromosome segregation errors. Merotelic kinetochore attachments in aged oocytes cause aneuploidy and embryo developmental issues.
Area of Science:
- Reproductive biology
- Cell biology
- Genetics
Background:
- Mammalian oocytes undergo two meiotic divisions to produce haploid gametes.
- Chromosome segregation errors increase with age during meiosis I, but meiosis II in aging oocytes is less understood.
- The mechanism by which aneuploid oocytes evade the spindle assembly checkpoint (SAC) in aged mice remains unclear.
Purpose of the Study:
- To investigate the impact of aging on chromosome arrangement and segregation during oocyte meiosis II.
- To determine how aneuploid metaphase II (MII) oocytes from aged mice bypass the SAC.
- To identify the molecular mechanisms underlying age-related aneuploidy in oocytes and subsequent embryo development.
Main Methods:
- Comparative analysis of metaphase II (MII) oocytes from young and naturally aged mice.
- Microscopic observation of chromosome arrangement, kinetochore-microtubule attachments, and spindle assembly checkpoint (SAC) activity.
- Parthenogenetic activation of oocytes to assess meiosis II progression and early embryonic development.
- Kinetochore-microtubule interaction analysis in aged oocytes.
Main Results:
- Aged MII oocytes exhibit significant errors in chromosome arrangement and configuration compared to young oocytes.
- Despite chromosomal errors, aged oocytes initiate and complete anaphase II, forming 2-cell embryos after parthenogenetic activation.
- Merotelic kinetochore attachment is more frequent in aged oocytes, stabilizing kinetochore-microtubule interactions and leading to SAC inactivation.
- This merotelic attachment persists through anaphase II, causing chromosome lagging, trailing, and delayed completion, resulting in aneuploidy.
Conclusions:
- Merotelic kinetochore attachment in oocyte meiosis II is a primary driver of age-related genetic instability.
- This mechanism contributes significantly to age-dependent aneuploidy in oocytes and subsequent embryo dysplasia.
- Understanding these age-related defects is crucial for addressing infertility and developmental abnormalities in aging populations.
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