Assisted Conception and Early Development
The overall purpose of the studies grouped under this heading is to improve the management of human infertility by evaluating the causes of diminished gamete quality and resolving the impact of this damage on the developmental potential of the embryo.
Proteomic and Metabolomic Analyses of Gamete and Embryo quality
This clinically-orientated project research project involves the development of a close interface with collaborators in assisted conception clinics to refine our understanding of gamete and embryo quality. This project will use state-of-the-art techniques in metabolomics and proteomics to define the molecular basis of impaired gamete function and to identify markers for the assessment of embryo quality. Current emphasis is on resolving the molecular basis of impaired gamete interaction at fertilization and the role of oxidative stress in the disruption of fertilization and impaired embryonic development. This project would provide training in advanced mass spectrometry as well as insights into the assisted conception industry.
Preliminary clinical data is available to suggest that infertile males generate gametes that possess methylation defects that might have an impact on the developmental potential of the embryo and the health and well being of the subsequent offspring. These defects are characterized by hypomethylation of key sites, which we have hypothesised is due to oxidative damage to the corresponding CpG islands. High-throughput DNA methylation profiling will be used to screen for genome wide methylation defects in the gametes of infertile men. These profiles will subsequently be correlated with presence of oxidative base damage to the sperm DNA. In addition we shall correlate any defects seen in the methylation profiles with the developmental potential of the embryo and the normality of DNA methylation in the offspring.