Ageing effects on oocytes and novel approaches for improving oocyte quality (NHMRC Grants APP1103689 and APP1122484)

Oocyte quality declines markedly with ageing leading to increased levels of chromosomally abnormal pregnancies (e.g. Down’s syndrome), infertility and miscarriage. However, little is known regarding the key molecular factors in oocytes that succumb with ageing. To address this, we are analysing human and mouse oocytes from reproductively aged females. We are also using transgenic animals over-expressing genes that could be involved in delaying the ageing process. In this way we are identifying key factors that are vulnerable to ageing and that underpin oocyte health. We are using this knowledge to design novel interventions for preventing or reversing ageing-induced deterioration.
 

Molecular control of meiotic maturation

A prominent feature of aged oocytes, and poor-quality oocytes in general, is their propensity to mis-segregate chromosomes. The resulting embryonic aneuploidy is catastrophic to pregnancy success. Intriguingly, the majority of such errors arise specifically during meiosis I – the first of the two meiotic divisions required to halve the chromosome complement in preparation for fertilisation. We are therefore deciphering the key regulators overseeing chromosome segregation during female meiosis I. We use loss-of-function and gain-of-function genetic approaches combined with state-of-the-art time-lapse confocal imaging to track the entire process of spindle assembly and chromosome segregation during the several hours of meiosis I.

Non-destructive methods for oocyte selection (NHMRC Grant APP1078134)

The per-oocyte pregnancy rate during IVF is surprisingly low with 7% or less of all oocytes producing a live-birth. Because of this low efficiency, multiple cycles of IVF are often required and in many areas of the world, multiple embryos are replaced leading to unacceptable rates of high-risk multiple pregnancies. Techniques capable of earmarking the best quality oocytes would greatly streamline IVF practice. In collaboration with our IVF partners we are therefore investigating approaches for identifying the best oocytes, for instance, by studying the vestigial by-products of meiotic maturation known as polar bodies.

Protecting oocytes to preserve female fertility after cancer (NHMRC Grant APP1103689)

The development of highly effective cancer treatments has dramatically improved cancer survivorship. Consequently, following completion of cancer treatment many reproductively aged women hope to start families. Unfortunately, however, many effective chemotherapy regimens are extremely toxic to oocytes resulting in infertility and premature menopause. We are investigating the cellular basis for oocyte death during cancer treatment and are exploring novel methods for enabling oocytes to survive in order to preserve fertility.