About the Project
Female fertility decreases with age, with decline in fertility rates observed from the age of 35 (Gruhn et al., 2019). Social changes causing delayed parenthood and increasing average age of IVF patients highlight the need for understanding how advancing female age affects their reproductive functions. The reduction of fertility rates in older women is largely caused by the increased risk of aneuploidy, or abnormal number of chromosomes, in oocytes. Such oocytes are often incapable of normal…
development and may cause infertility, pregnancy loss, or developmental syndromes in children (e.g. Down’s). Abnormal number of chromosomes in oocytes arises due to errors in chromosome segregation as oocyte matures, which are surprisingly common, and additionally increase in frequency as women age. While some mechanisms contributing to this have been identified (see e.g. Mihalas et al., 2024), the overall understanding of the effect of ageing on human oocytes is lacking.
This project will investigate how chromosome segregation changes in oocytes from women of different ages. We will focus on the structures that orchestrate chromosome movement during meiosis: the microtubule-based meiotic spindle and the kinetochores, specialised sites where microtubules attach to chromosomes. Recent advancements have suggested a link between the error-prone process of spindle formation in oocytes and the role of the outer layer of the kinetochore (fibrous corona; Wu et al., 2023). Based on that finding, the student will investigate how kinetochores age building on preliminary work revealing how the corona structure fragments as eggs age. To do this the student will obtain immature human oocytes donated to research from our partner IVF unit and study them using a variety of techniques with focus on high resolution imaging, including live imaging of meiosis. Through this work, we aim to test interventions that may restore corona integrity and improve chromosome segregation fidelity in oocytes.
