Regulation of ovarian function

2013年，加拿大猪肉行业生产了2700万头猪，出口了31亿美元的产品。繁殖效率是猪肉行业盈利的关键因素之一，然而，与更常用的啮齿动物模型相比，我们对这种农业上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，从而开发出提高母猪生产力的策略。卵巢的两个主要功能是产生合格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行。MicroRNAs(MiRNAs)是一种小的非编码RNA，它与目标转录物的3‘非翻译区(3’UTR)相互作用，抑制表达。由于每个miRNA能够靶向多个基因，miRNA被认为是各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还没有被探索。大多数卵巢miRNAs的靶基因目前尚不清楚，这些小RNA的功能也是未知的。我们最近证实miR-378调节猪卵巢颗粒细胞雌激素的产生。这种微RNA还抑制孕酮受体的表达、卵丘的扩张和卵母细胞的成熟。我们计划研究特定miRNAs在卵泡发育过程中的阶段依赖性表达，以确定卵泡期和细胞类型miRNA的表达模式。这些结果将使我们能够使用我们实验室建立的方法来测试关于特定miRNAs功能的假设，包括慢病毒介导的颗粒细胞过表达、细胞凋亡和增殖检测以及ELISA。然后，这项工作将扩大到观察miRNA在卵母细胞成熟和胚胎发育中的作用。最后，卵泡细胞中miRNA的调节如何影响卵巢的生理和生育能力将在体内得到证实。了解miRNA对卵巢功能的调控可能会导致提高母猪繁殖力的策略。由于单个miRNA可能具有调节整个分子途径的活性的潜力，这些分子可能与有吸引力的遗传标记相连，用于选择潜在母猪所需的生殖性状或针对其进行选择，以招募到育种群体。

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.*****************