Tulay, P; (2013) Investigation of DNA repair gene expression and protein function in human oocytes and preimplantation embryos. Doctoral thesis (PhD), UCL (University College London).

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Abstract

This study investigated microRNA and mRNA expression and protein function associated with DNA repair in human oocytes and embryos. MicroRNAs have been shown to down-regulate and in some cases to stabilise the expression of several genes including repair genes. The first aim of this study was to analyse the differences in the expression of microRNAs and their target mRNAs involved in repair. This study showed that the levels of expression of most of the repair gene mRNAs were higher in oocytes than blastocysts and this was also the case for many of the miRNAs. The correlation analysis of the miRNA and their target expression levels in the oocyte and blastocyst samples were restricted by the limited size and number of available samples, but indicated no clear cut pattern of differences in relative expression. Differential methylation of parental genomes that may lead to differential parental gene expression had been observed previously in mouse embryos. The second aim of this study was to investigate differential parental expression of BRCA1 in human embryos. This study showed that differential paternal BRCA1 expression exists in the early developing embryos. Moreover, embryos with paternally inherited BRCA mutations were shown to develop more slowly compared to embryos with maternally inherited BRCA1 mutations. Both differential expression and the developmental delay may be associated with differential methylation of parental genomes. Expression analyses are crucial to investigate the potential function of genes. However these analyses do not provide information on the functionality of biological processes. Therefore, the final part of this study aimed to develop a sensitive functional assay detecting mismatch repair efficiency in preimplantation embryos. In this study a unique assay was developed to detect mismatch repair efficiency using small amounts of nuclear/whole cell extracts and experiments demonstrated that mismatch repair is active in mouse and human blastocysts.

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