Grant: CIHR Fellowship

One of the major causes of pregnancy loss and birth defects such as Down Syndrome is a defect with the woman's egg, whereby the egg has too few or too many chromosomes. The chance of a woman's egg having the wrong number of chromosomes increases as she gets older, and thus is the primary cause of female infertility in women of advancing maternal age. However, why eggs from older women are more prone to having an abnormal number of chromosomes than eggs from younger women is unknown. This study will test whether age causes problems with the way in which chromosomes interact with the spindle, the structure within the egg that physically binds to the chromosomes. To do this, we will use eggs from old mice, which exhibit very similar age-related defects in chromosome number as women in their 40s, thus serving as an excellent model to study human infertility. We will directly manipulate specific proteins essential for spindle mechanics to see if we can affect the old eggs to make sure they have the correct number of chromosomes. A major bottleneck in reproductive biology research is the inability to translate findings to the clinical setting, due largely in part to the precious nature of reproductive samples. Excitingly, this proposal will directly translate our findings from mice to humans, as we will have rare access to human eggs obtained from our newly established collaboration with an in vitro fertilisation clinic. As the age at which women are choosing to start a family in Canada has risen substantially over the past 30 years, and this trend is set to continue, the results of this proposal will therefore have a significant impact upon fertility and child health over the coming decades.