Grant: Project Grant

A major cause of the decline in fertility experienced by women in their 30s and 40s is a decrease in the quality of the egg. Specifically, it is known that eggs of older women are more likely to contain the wrong number of chromosomes - a state known as aneuploidy. These aneuploid eggs rarely give rise to a healthy offspring. To understand how aneuploidy arises in oocytes, we need to understand a process known as chromosome segregation, which determines which chromosomes are delivered to the egg as it develops. Here we will study this process, focussing on a key structure termed the 'kinetochore'. We have preliminary data that suggest that defects in the kinetochore may contribute to aneuploidy in oocytes, especially in older females. Our experiments in particular make use of cutting edge microscopy approaches. A majority of our experiments will be performed using mouse oocytes as a model system, and a more restricted number of key experiments will be performed on spare human oocytes from women undergoing fertility treatments. The 'immature' oocytes that we will use are not useful for the fertility treatment and would otherwise be discarded, but are ideal for our investigations. Overall we expect to find that the kinetochore is a major culprit in age-related infertility in women.