Oocyte ageing and its cellular basis

Area of Science:

• Reproductive Biology
• Cell Biology
• Genetics

Background:

• Aneuploidy, an abnormal chromosome number, is highly prevalent in oocytes from aged individuals.
• The precise cellular mechanisms driving oocyte aneuploidy with increasing maternal age remain incompletely understood.

Purpose of the Study:

• To elucidate the cellular origins and contributing factors of aneuploidy in aged human oocytes.
• To identify key events during meiosis that lead to chromosome mis-segregation.

Main Methods:

• Analysis of cytogenetic data from aged human oocytes and embryos from assisted reproduction (ART).
• Review of experimental models investigating meiotic errors and chromosome cohesion.
• Examination of the spindle assembly checkpoint (SAC) function in aged oocytes.

Main Results:

• Meiosis I errors, especially precocious chromatid separation and loss of chromosome cohesion, are primary drivers of aneuploidy.
• Aged oocytes exhibit a more permissive SAC and altered gene expression, hindering proper chromosome attachment.
• Mitochondrial dysfunction, influenced by maternal age and stimulation, further exacerbates spindle aberrations and segregation errors.

Conclusions:

• Loss of chromosome cohesion is a critical, irreversible risk factor for aneuploidy in aged oocytes.
• A combination of permissive SAC, risky recombination, altered gene expression, and mitochondrial dysfunction synergistically increases meiotic error susceptibility.
• Lifestyle interventions like caloric restriction and antioxidants show potential in mitigating aneuploidy in aged oocytes.