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Cell Cycle. 2017 Aug 3;16(15):1404-1413. doi: 10.1080/15384101.2017.1327488. Epub 2017 Jun 7.

Merotelic kinetochore attachment in oocyte meiosis II causes sister chromatids segregation errors in aged mice.

Author information

1
a State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology , Chinese Academy of Sciences , Beijing , China.
2
b University of Chinese Academy of Sciences , Beijing , China.
3
c Institute of Reproductive Medicine , School of Medicine, Nantong University , Nantong, Jiangsu , 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.

KEYWORDS:

aging; cohesion; kinetochore-microtubule attachment; meiosis II; oocytes; sister chromatids

PMID:
28590163
PMCID:
PMC5553406
DOI:
10.1080/15384101.2017.1327488
[Indexed for MEDLINE]
Free PMC Article

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