Small RNA pathways in the regulation of bovine oocyte maturation and early embryogenesis

建议摘要

Summary of Proposal The Canadian cattle industry contributes billions of dollars and thousands of jobs annually to the economy. Animal productivity depends on fertility and early pregnancy failure is a major factor limiting productivity in this area. In cattle, as in other mammals, early embryonic development represents a critical point in the establishment of successful pregnancies. From a scientific standpoint, the exploration of mechanisms that control embryonic growth and development provide fascinating insights into some of the most fundamental biological questions as they apply to many different species. Growth, development and viability of the embryo depends on multiple factors, the most important of which is the strict, well-timed turning "on" and "off" of specific genes in the animal's DNA. This process controls the level of "gene expression" which can be loosely defined as the actual level of specific RNA or protein molecules that are present in an animal's cell at a particular time. Embryos that have abnormal control of gene expression develop abnormally or fail to develop at all. Control of gene expression is very complicated and involves different pathways that increase or decrease the overall levels of the RNAs that encode specific proteins in cells, tissues or organisms. These include factors that change the amount of messenger RNA (mRNA) that is produced (transcription) and factors that change the rate at which those same mRNAs are destroyed or are used as templates for the production of protein. The pathways in animals that use the inhibition of protein production or cause accelerated decay of RNA in order to change gene expression are called "post-transcriptional" mechanisms or pathways. This research program will investigate post-transcriptional pathways in very young cow embryos that control the expression of important genes, and evaluate how these processes impact their development and survival. Using cutting-edge molecular biology techniques, and bovine embryos generated by in vitro fertilization, our studies will examine the roles of very potent, specific small RNA molecules called microRNAs that regulate the expression of genes in oocytes and embryos through these pathways. Differences in the levels or activities of these microRNAs are very likely to influence pregnancy and development and will be identified and examined in detail. These studies should help reveal important new pathways that control female fertility and early embryo development in the cow. Ultimately, we hope that this knowledge will contribute directly to strategies that improve fertility in cattle.