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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HD044778-04
Application #
7120056
Study Section
Special Emphasis Panel (ZHD1-DRG-D (18))
Program Officer
Rankin, Tracy L
Project Start
2003-09-25
Project End
2008-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
4
Fiscal Year
2006
Total Cost
$319,812
Indirect Cost
Name
Monash University
Department
Type
DUNS #
753252691
City
Victoria
State
Country
Australia
Zip Code
3800
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Wood, Bayden R; Chernenko, Tatyana; Matthaus, Christian et al. (2008) Shedding new light on the molecular architecture of oocytes using a combination of synchrotron Fourier transform-infrared and Raman spectroscopic mapping. Anal Chem 80:9065-72
Lacham-Kaplan, Orly; Trounson, Alan (2008) Reduced developmental competence of immature, in-vitro matured and postovulatory aged mouse oocytes following IVF and ICSI. Reprod Biol Endocrinol 6:58
Rosenfeld, Jeffrey V; Bandopadhayay, Prateek; Goldschlager, Tony et al. (2008) The Ethics of the Treatment of Spinal Cord Injury: Stem Cell Transplants, Motor Neuroprosthetics, and Social Equity. Top Spinal Cord Inj Rehabil 14:76-88
Jones, Gayle M; Song, Bi; Cram, David S et al. (2007) Optimization of a microarray based approach for deriving representative gene expression profiles from human oocytes. Mol Reprod Dev 74:8-17
Serafica, Maria D; Goto, Tetsuya; Trounson, Alan O (2005) Transcripts from a human primordial follicle cDNA library. Hum Reprod 20:2074-91