Regulation of ovarian function

卵巢功能的调节

• 批准号: RGPIN-2015-05823
• 负责人: Li, Julang
• 金额: $ 2.91万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=657458
• 关键词: Regulation; ovarian; function

Canada's pork industry produced 27 million pigs and exported 3.1 billion dollars of product worldwide in 2013. Reproductive efficiency is one of the key profitability components of the pork industry, however, compared to the more commonly used rodent models, our knowledge of ovarian physiology in this agriculturally important species is limited. The long term goal of my research program is to improve our understanding of pig ovarian physiology and thereby develop strategies to enhance sow productivity.******Two major functions of the ovary are the generation of competent oocytes and the production of hormones. These processes require coordinated gene expression within ovarian cells to operate correctly. MicroRNAs (miRNAs) are small non-coding RNAs that interact with the 3' untranslated region (3'UTR) of their target transcripts to suppress expression. With each miRNA able to target multiple genes, miRNA are known as important regulators of diverse physiological processes. However, the science concerning miRNAs in the ovary is largely unexplored. The target genes of most ovarian miRNAs are currently unknown, as are the functions of these small RNAs. We have recently demonstrated that miR-378 regulates production of the hormone estradiol in pig ovarian granulosa cells. This microRNA also suppressed progesterone receptor expression, cumulus expansion and oocyte maturation. We plan to investigate the stage-dependent expression of specific miRNAs during ovarian follicle development to identify follicular-stage and cell-type patterns of miRNA expression. These results will allow us to test hypotheses about the functions of specific miRNAs using approaches established in our lab, including lentivirus-mediated over expression, apoptosis and proliferation assays, and ELISA, in granulosa cells. This work will then be expanded to observe the role of miRNA in oocyte maturation and embryo development. Finally, how miRNA regulation in ovarian follicle cells affects ovarian physiology and fertility will be confirmed in vivo. Understanding miRNA regulation of ovarian function may lead to strategies to enhance sow fertility. Since a single miRNA may have the potential to regulate the activity of an entire molecular pathway, these molecules may be linked with attractive genetic markers for selection towards or against desired reproductive traits in potential gilts for recruiting into breeding stock.*****************

2013年，加拿大的猪肉产业生产了2700万头猪，出口了31亿美元的产品。繁殖效率是猪肉行业的关键盈利组成部分之一，然而，与更常用的啮齿动物模型相比，我们对这一农业重要物种的卵巢生理学知识有限。我的研究计划的长期目标是提高我们对猪卵巢生理学的理解，从而制定提高母猪生产力的策略。卵巢的两个主要功能是产生有能力的卵母细胞和产生激素。这些过程需要卵巢细胞内协调的基因表达才能正确运作。微小RNA（microRNAs，miRNAs）是一类小的非编码RNA，它与靶基因转录本的3'非翻译区（3' UTR）相互作用，从而抑制其表达。由于每个miRNA都能靶向多个基因，因此miRNA被认为是多种生理过程的重要调节因子。然而，关于卵巢中miRNAs的科学在很大程度上尚未探索。大多数卵巢miRNAs的靶基因目前尚不清楚，这些小RNA的功能也是如此。我们最近证明了miR-378调节猪卵巢颗粒细胞中激素雌二醇的产生。这种microRNA还抑制孕酮受体表达、卵丘扩张和卵母细胞成熟。我们计划研究特定miRNA在卵泡发育过程中的阶段依赖性表达，以确定卵泡阶段和细胞类型的miRNA表达模式。这些结果将使我们能够使用我们实验室建立的方法，包括慢病毒介导的过表达，凋亡和增殖测定，以及ELISA，在颗粒细胞中测试关于特定miRNA功能的假设。这项工作将扩展到观察miRNA在卵母细胞成熟和胚胎发育中的作用。最后，卵泡细胞中的miRNA调控如何影响卵巢生理和生育力将在体内得到证实。了解卵巢功能的miRNA调控可能会导致提高母猪生育力的策略。由于单个miRNA可能具有调节整个分子途径的活性的潜力，因此这些分子可能与有吸引力的遗传标记相关联，用于在潜在后备母猪中朝向或反对所需的繁殖性状进行选择，以招募到种猪中。