Importance of the interactions between intracellular signalling pathways during sperm acquisition of fertilizing competence.

精子获得受精能力过程中细胞内信号通路之间相互作用的重要性。

• 批准号: RGPIN-2015-06616
• 负责人: Leclerc, Pierre
• 金额: $ 1.75万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=614256
• 关键词: Importance; interactions; between; intracellular; signalling

Spermatozoa are highly differentiated cells which only role is to fertilize the egg in order to produce a new individual. Although structurally complete at the exit of the testis, they must reside in the female reproductive tract where they undergo surface and intracellular modifications, named as a whole as capacitation, to become fully fertilization competent. My research program is devoted to further investigate sperm intracellular events during the acquisition of sperm fertilizing ability and to better characterize how spermatozoa become competent to successfully interact with the egg, fertilize it, and initiate the early development of a genetically unique individual. Although the requirement for Ca2+ for these events is known for many years, the mechanisms that control its intracellular levels and its exact roles during sperm capacitation remain to be elucidated. In this research proposal, we will investigate the biochemical events that are involved in the storage of intracellular Ca2+, which will be necessary later when the spermatozoa will interact with the egg. Another objective is to investigate further the importance of Ca2+ in sperm capacitation, such as the dynamics of actin polymerization and depolymerization, and to determine whether it involves or is affected by protein tyrosine phosphorylation. The changes in sperm intracellular biochemical reactions elucidated in this research program will undoubtedly lead to a better knowledge on sperm fertilizing ability and sperm/egg interactions, which would ultimately help to detect and have impact on fertility problems encountered in endangered animal species where the quality of semen and of spermatozoa are often defective. Impact could also be applicable to humans as well since lifestyle and environment have strong impacts on sperm fertilizing ability and, therefore, male fertility. Highly importantly, my research program is directly related to agricultural industries like dairy or meat, which depend on successful reproduction. This is further emphasized by the importance of artificial insemination in livestock reproduction, more specifically when cryopreserved semen is used. Although this process gives numerous advantages, it affects sperm viability and fertilizing ability, which explains why more spermatozoa are required per insemination units when compared with fresh non-frozen semen. Therefore, results obtained through this research proposal can ultimately results in changes in the cryopreservation process that will ultimately reduce the number of spermatozoa per insemination unit without affecting fertilization rate.

精子是高度分化的细胞，它的唯一作用是使卵子受精，以产生一个新的个体。尽管它们在睾丸出口处结构完整，但它们必须驻留在女性生殖道中，在那里它们经历表面和细胞内的修饰，作为一个整体被称为获能，才能完全具有受精能力。我的研究项目致力于进一步研究精子受精能力获得过程中的精子细胞内事件，并更好地表征精子如何能够成功地与卵子相互作用，使其受精，并启动基因独特个体的早期发育。尽管这些事件对Ca2+的需求已经知道很多年了，但控制其细胞内水平的机制及其在精子获能过程中的确切作用仍有待阐明。在这项研究计划中，我们将研究细胞内Ca2+储存的生化事件，这将是精子与卵子相互作用时所必需的。另一个目的是进一步研究Ca2+在精子获能中的重要性，如肌动蛋白聚合和解聚的动力学，并确定它是否涉及或受蛋白酪氨酸磷酸化的影响。本研究项目所阐明的精子细胞内生化反应的变化，无疑将有助于更好地了解精子受精能力和精子/卵子相互作用，最终有助于发现并影响精液和精子质量经常存在缺陷的濒危动物物种的生育问题。这种影响也适用于人类，因为生活方式和环境对精子的受精能力有很大的影响，因此也会影响男性的生育能力。非常重要的是，我的研究项目与农业直接相关，比如乳制品或肉类，这些都依赖于成功的繁殖。这进一步强调了人工授精在牲畜繁殖中的重要性，特别是当使用冷冻保存的精液时。尽管这个过程有很多优点，但它会影响精子的生存能力和受精能力，这就解释了为什么与新鲜的非冷冻精液相比，每个授精单位需要更多的精子。因此，通过本研究方案获得的结果最终可以导致冷冻保存过程的改变，从而最终减少每个授精单位的精子数量，而不影响受精率。