Molecular Markers of Oocyte Quality and Competence

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DESCRIPTION (provided by applicant): This application focuses on establishing identifiable markers of high quality mammalian oocytes and embryos that have full developmental potential. Our hypothesis is that a high quality oocyte is an important starting point for the development of healthy offspring, and that low oocyte quality can lead to infertility, abnormal embryonic and fetal development and possibly long-term adult diseases and disorders in the offspring. The applicants have a long, distinguished, history of quality research into oocyte and follicular growth and development, oocyte, embryonic stem cell and embryo manipulation; including programming, reprogramming, IVF and embryo manipulation and culture and cryopreservation, placentation and the study of the Barker Hypothesis (the fetal origins of adult diseases). Our access to the Maccine Primate Facility at Bogor and the new National Non Human Primate Facility at Monash University, together with our association with a world leading innovative IVF clinic, Monash IVF, means that our advances using unique animal models will be rapidly applied to the clinical arena. This application's goal is to discover measurable or identifiable characteristics that can be used to evaluate the quality of normal and abnormal human oocytes and embryos. This will be achieved by increasing our understanding of the genetics, epigenetics, cell and molecular biology and proteomics of normal and manipulated mammalian oocytes. Ovaries containing oocytes that have been exposed to maternal lifestyle diseases (diabetes and obesity) and ageing before and after xenotransplantation to healthy recipients will be compared to the criteria that we will establish for normal oocytes and embryos in studies undertaken in both in vitro and in vivo animal models. Our access to primate models of diabetes, obesity and ageing to complement our murine studies are a significant feature of this application. We will establish protein and gene expression profiles correlated with the ability of an oocyte to resume and complete meiosis, fertilise and subsequently develop into a viable embryo, both during normal development and in response to artificial stimulation. This should provide the opportunity to improve outcomes for both in vitro maturation (IVM) and in vitro fertilisation (IVF) cycles. The ultimate beneficiaries of this research will be women who have difficulty attaining healthy pregnancies and healthy offspring because of low egg quality.