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

提案摘要 加拿大养牛业每年为经济贡献数十亿美元和数千个就业机会。动物的生产力取决于生育能力，早孕失败是限制这一领域生产力的主要因素。牛和其他哺乳动物一样，早期胚胎发育是成功怀孕的关键点。从科学的角度来看，探索控制胚胎生长和发育的机制为一些最基本的生物学问题提供了迷人的见解，因为它们适用于许多不同的物种。胚胎的生长、发育和生存能力取决于多种因素，其中最重要的是动物DNA中特定基因的严格、适时的“开启”和“关闭”。这一过程控制着“基因表达”的水平，基因表达可以粗略地定义为在特定时间存在于动物细胞中的特定RNA或蛋白质分子的实际水平。基因表达控制异常的胚胎发育异常或根本不能发育。基因表达的控制非常复杂，涉及不同的途径，这些途径增加或减少编码细胞、组织或生物体中特定蛋白质的RNA的总体水平。这些因素包括改变产生（转录）的信使RNA（mRNA）的量的因素，以及改变这些相同mRNA被破坏或用作蛋白质产生模板的速率的因素。在动物中，通过抑制蛋白质产生或加速RNA降解来改变基因表达的途径被称为“转录后”机制或途径。该研究计划将研究控制重要基因表达的非常年轻的奶牛胚胎中的转录后途径，并评估这些过程如何影响它们的发育和存活。利用尖端的分子生物学技术和体外受精产生的牛胚胎，我们的研究将研究称为microRNA的非常有效的特异性小RNA分子的作用，这些分子通过这些途径调节卵母细胞和胚胎中基因的表达。这些microRNA水平或活性的差异很可能影响妊娠和发育，并将被详细鉴定和检查。这些研究应该有助于揭示控制奶牛雌性生育力和早期胚胎发育的重要新途径。最终，我们希望这些知识将直接有助于提高牛生育力的策略。

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.