Age-dependent integrity of the meiotic spindle assembly checkpoint in females requires Aurora kinase B

Cecilia S. Blengini, Alexandra L. Nguyen, Mansour Aboelenain, Karen Schindler

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


A hallmark of advanced maternal age is a significant increase in meiotic chromosome segregation errors, resulting in early miscarriages and congenital disorders. These errors most frequently occur during meiosis I (MI). The spindle assembly checkpoint (SAC) prevents chromosome segregation errors by arresting the cell cycle until proper chromosome alignment is achieved. Unlike in mitosis, the SAC in oocytes is desensitized, allowing chromosome segregation in the presence of improperly aligned chromosomes. Whether SAC integrity further deteriorates with advancing maternal age, and if this decline contributes to increased segregation errors remains a fundamental question. In somatic cells, activation of the SAC depends upon Aurora kinase B (AURKB), which functions to monitor kinetochore–microtubule attachments and recruit SAC regulator proteins. In mice, oocyte-specific deletion of AURKB (Aurkb cKO) results in an increased production of aneuploid metaphase II-arrested eggs and premature age-related infertility. Here, we aimed to understand the cause of the short reproductive lifespan and hypothesized that SAC integrity was compromised. In comparing oocytes from young and sexually mature Aurkb cKO females, we found that SAC integrity becomes compromised rapidly with maternal age. We show that the increased desensitization of the SAC is driven by reduced expression of MAD2, ZW10 and Securin proteins, key contributors to the SAC response pathway. The reduced expression of these proteins is the result of altered protein homeostasis, likely caused by the accumulation of reactive oxygen species. Taken together, our results demonstrate a novel function for AURKB in preserving the female reproductive lifespan possibly by protecting oocytes from oxidative stress.

Original languageEnglish (US)
Article numbere13489
JournalAging cell
Issue number11
StatePublished - Nov 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Aging
  • Cell Biology


  • Aurora kinase B
  • infertility
  • reactive oxygen species
  • reproductive aging
  • spindle assembly checkpoint


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