Cell division cycle 23 is required for mouse oocyte meiotic maturation

Area of Science:

• Reproductive Biology
• Cell Biology
• Genetics

Background:

• Accurate chromosome segregation during oocyte meiosis is essential for successful mammalian reproduction.
• The Anaphase Promoting Complex/Cyclosome (APC/C) is a key regulator of the metaphase-to-anaphase transition.

Purpose of the Study:

• To investigate the role of cell division cycle 23 (Cdc23, also known as APC8) in regulating chromosome segregation during mouse oocyte meiosis.
• To elucidate the molecular mechanisms by which Cdc23 influences meiotic progression and accuracy.

Main Methods:

• Utilized Cdc23 siRNA microinjection to deplete Cdc23 in mouse oocytes.
• Observed meiotic spindle morphology, chromosome alignment, and segregation patterns.
• Assessed the spindle assembly checkpoint (SAC) activity and degradation of key proteins like Cyclin B1 and securin.
• Investigated the effects of inhibiting the SAC protein Msp1 in Cdc23 knockdown oocytes.

Main Results:

• Cdc23 localizes to the meiotic spindle and its depletion reduces the metaphase-to-anaphase transition rate.
• Loss of Cdc23 leads to abnormal spindles, misaligned chromosomes, homologous chromosome segregation errors, and aneuploid oocytes.
• Cdc23 knockdown disrupts SAC inactivation and inhibits the degradation of Cyclin B1 and securin.
• Inhibition of Msp1 partially rescues polar body extrusion and reduces securin accumulation in Cdc23-deficient oocytes.

Conclusions:

• Cdc23 is indispensable for proper chromosome segregation in meiotic mouse oocytes.
• Cdc23 regulates chromosome segregation by controlling SAC activity and facilitating the degradation of Cyclin B1 and securin.
• These findings highlight Cdc23's critical role in ensuring meiotic fidelity and preventing aneuploidy in oocytes.