Designing protein-based artificial kinetochores as decoys to prevent meiotic errors in oocytes

Area of Science:

• Cell Biology
• Reproductive Biology
• Biotechnology

Background:

• Chromosome mis-segregation during oocyte meiosis leads to miscarriages and congenital diseases.
• Age-related premature chromosome separation is a primary driver of meiotic errors.
• Current methods for preventing premature chromosome separation are insufficient.

Purpose of the Study:

• To design and evaluate protein-based artificial kinetochores as decoys to prevent premature chromosome separation.
• To investigate the efficacy of these artificial kinetochores in aged mouse oocytes.
• To explore a novel strategy for mitigating age-associated meiotic errors.

Main Methods:

• Engineered submicroscale clusters of NDC80-NUF2-tethered protein particles to form artificial kinetochores.
• Utilized artificial kinetochores to compete with chromosomal kinetochores for binding to HURP-decorated microtubules.
• Assessed the impact of artificial kinetochores on microtubule-chromosome interactions and aneuploidy in aged mouse oocytes.

Main Results:

• Artificial kinetochores successfully established a biorientation-like state.
• Competition reduced excessive microtubule pulling forces on chromosomes.
• Demonstrated effective prevention of premature chromosome separation in both meiosis I and II in aged oocytes.
• Suppressed egg aneuploidy, indicating improved meiotic fidelity.

Conclusions:

• Protein-based artificial kinetochores offer a viable decoy strategy to prevent age-associated meiotic errors.
• This approach effectively mitigates premature chromosome separation and subsequent aneuploidy in oocytes.
• The study presents a promising biocompatible technology for enhancing reproductive health and preventing congenital diseases.