Prolonged metaphase II arrest weakens Aurora B/C-dependent error correction in mouse oocytes.

Area of Science:

• Cell Biology
• Genetics
• Reproductive Biology

Background:

• Chromosome segregation errors are common in mammalian oocytes during meiosis.
• The spindle assembly checkpoint (SAC) and error correction mechanisms are crucial for accurate chromosome segregation.
• Knowledge of these mechanisms during meiosis II is limited, especially concerning prolonged metaphase II arrest.

Purpose of the Study:

• To investigate the functionality of Aurora B/C-dependent error correction in detecting and correcting low inter-kinetochore tension during meiosis II.
• To determine if prolonged metaphase II arrest affects the oocyte's ability to correct chromosome misattachments.

Main Methods:

• Utilized low-dose STLC (monastrol) to induce low inter-kinetochore tension in early metaphase II.
• Monitored SAC activation and anaphase II progression in response to induced low tension.
• Assessed Aurora B/C kinase activity and PP2A accumulation at kinetochores during prolonged metaphase II arrest.

Main Results:

• Low inter-kinetochore tension in early metaphase II activates Aurora B/C, leading to microtubule detachment and anaphase II delay via SAC activation.
• During prolonged metaphase II arrest, Aurora B/C activity is insufficient to correct low-tension attachments due to PP2A accumulation at kinetochores.
• Consequently, the SAC is not activated, and sister chromatids segregate without delay, even with misattachments.

Conclusions:

• Mammalian oocytes possess an error correction mechanism for chromosome misattachments in early meiosis II.
• Prolonged metaphase II arrest compromises this error correction, rendering oocytes unable to discriminate correct from incorrect attachments.
• This impairment during arrest may lead to persistent chromosome segregation errors and aneuploidy in oocytes awaiting fertilization.