Why females ovulate more aneuploid eggs as they get older. — ASN Events

Why females ovulate more aneuploid eggs as they get older. (#140)

Keith Jones 1
  1. University of Newcastle, Callaghan, NSW, Australia

Mammalian oocytes have to divide their chromosomes twice during meiosis in order to generate a haploid egg. Union with the haploid sperm then creates a diploid embryo. Despite the essential need to segregate chromosomes faithfully it is remarkable that oocytes do this so poorly in comparison to sperm, as well as all somatic cells that undergo mitosis with great fidelity. In nearly all instances the outcome of such unfaithful activity is an embryo destined to die at some stage during embryogenesis, dependent on which chromosome(s) is affected. 

The mis-segregation of chromosomes in oocytes is believed to be an error principally associated with the first meiotic division rather than the second. These errors rise dramatically with female age, such that in older women the majority of eggs ovulated can be aneuploid. The reasons for aging being a risk factor are only now coming to light and they derive from a loss in the cohesive ties holding chromosomes together.

Research in our group has used mice, as a mammalian model, to study in detail why oocytes during meiosis I are susceptible to aneuploidy, and why aging exacerbates such errors. We have developed techniques to follow chromosome movements in live oocytes as they happen in real time over a period of several hours, with a temporal resolution of just a few minutes. The ability to perform this tracking has led us to discover what we consider to be an important defect in oocytes that allows aneuploidy to happen more often than it should. In addition by using these techniques to examine oocytes from aged mice we have uncovered the segregation defect associated with aging. These recent findings from our group are in agreement with the current models that suggest chromosome cohesion loss causes aneuploidy and by their real-time nature provide a deeper understanding of why female meiosis is so poor at faithful division.