Age-dependent aneuploidy in mammalian oocytes instigated at the second meiotic division.

Abstract

Ageing severely affects the chromosome segregation process in human oocytes resulting in aneuploidy, infertility and developmental disorders. A considerable amount of segregation errors in humans are introduced at the second meiotic division. We have here compared the chromosome segregation process in young adult and aged female mice during the second meiotic division. More than half of the oocytes in aged mice displayed chromosome segregation irregularities at anaphase II, resulting in dramatically increased level of aneuploidy in haploid gametes, from 4% in young adult mice to 30% in aged mice. We find that the post-metaphase II process that efficiently corrects aberrant kinetochore-microtubule attachments in oocytes in young adult mice is approximately 10-fold less efficient in aged mice, in particular affecting chromosomes that show small inter-centromere distances at the metaphase II stage in aged mice. Our results reveal that post-metaphase II processes have critical impact on age-dependent aneuploidy in mammalian eggs.