Na+/K+-ATPase and regulation of testis and sperm function

Na /K -ATP酶与睾丸和精子功能的调节

• 批准号: RGPIN-2020-04585
• 负责人: Thundathil, Jacob
• 金额: $ 3.42万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=763624
• 关键词: Na+; K+; ATPase; regulation; testis; Na+; K+; ATPase; regulation; testis

Global demand for food will increase substantially in the near future. Since even a modest increase in the reproductive rate in cattle substantially enhances meat and milk production, research to improve reproductive efficiency will substantially benefit the Canadian cattle industry and economy, with positive effects on global food production. In that regard, bull fertility is particularly relevant, as potentially millions of frozen semen doses from an elite bull can be used for breeding. Therefore, accurate prediction of fertility of these bulls is critical. Bulls traditionally classified as satisfactory breeders based on routine semen evaluation procedures vary in their fertility. Therefore, identification of molecular markers of fertility and evaluation of the genetic basis for variation in the content of these biomarkers among bulls will enable animal breeders and genetic companies to include this information in genetic selection of bulls at their early age. In that regard, long-term goal of my research program is elucidating regulation of male fertility. In my past research (supported by NSERC DG), I generated new knowledge that Sodium, Potassium ATPase (NKA) is involved in regulation of testis and sperm function in bulls, and proposed ATP1A4 (a member of NKA protein family exclusively present in the testis and sperm) as a fertility marker. This proposal is focused on understanding the molecular mechanisms by which ATP1A4 regulates bull fertility. We will determine the contribution of this protein in growth and division of testicular cells (Sertoli cells) that coordinate and support spermatogenesis (Objective 1). Since number of Sertoli cells in the adult testis is a determinant of semen production potential, results of our study will contribute to developing bull management strategies for increasing Sertoli cell number and their reproductive potential. We recently reported that ATP1A4 interacts with PLC ? (a protein critical for fertilization) during capacitation (final maturation of sperm in the female enabling fertilizing ability). However, physiological significance of this interaction and its consequences to capacitation and fertilization remains unknown, which will be investigated in this study (Objective 2). These results will improve efficiency of reproductive technologies relevant for genetic testing and selection of bulls at their earliest possible age for marketing their semen. We reported that ATP1A4 is synthesized in the sperm during capacitation. In this proposal, we will investigate the underlying molecular mechanisms (Objective 3). New knowledge generated in this study will have a high impact on the field of male fertility. Overall, these studies will create new knowledge, with important applications at an interdisciplinary level with high impact on global food production. I proposed to train 3 doctoral trainees and 5 summer students, preparing them for diverse careers.

在不久的将来，全球对粮食的需求将大大增加。由于即使牛的生殖率的适度提高也可以大大提高肉类和牛奶的生产，因此提高生殖效率的研究将基本上有益于加拿大牛业和经济，并对全球粮食生产产生积极影响。在这方面，牛的生育能力尤其重要，因为可能会使用精英公牛的数百万冷冻精液剂量来繁殖。因此，这些公牛的生育能力的准确预测至关重要。传统上，公牛根据常规精液评估程序被归类为令人满意的育种者，其生育能力各不相同。因此，鉴定生育能力的分子标记和评估公牛中这些生物标志物含量变化的遗传基础，将使动物育种者和遗传公司能够在牛群的遗传选择中包括这些信息。在这方面，我的研究计划的长期目标是阐明男性生育能力的调节。在我过去的研究（由NSERC DG支持）中，我产生了新的知识，即钠，钾ATPase（NKA）参与了公牛中的睾丸和精子功能的调节，并提出了ATP1A4（NKA蛋白质家族的成员，在睾丸和精子中独家存在）。该提案的重点是理解ATP1A4调节牛育能力的分子机制。我们将确定该蛋白在协调和支持精子发生的睾丸细胞（Sertoli细胞）生长和分裂中的贡献（目标1）。由于成人睾丸中的Sertoli细胞的数量是精液生产潜力的决定因素，因此我们的研究结果将有助于制定牛牛肉管理策略，以增加Sertoli细胞数量及其生殖潜力。我们最近报道ATP1A4与PLC相互作用？ （一种对受精至关重要的蛋白质）在电容过程中（女性实现施肥能力的精子的最终成熟）。但是，这种相互作用的生理意义及其对电容和受精的后果尚不清楚，这将在这项研究中进行研究（目标2）。这些结果将提高与基因测试和公牛的选择相关的生殖技术的效率，以便在营销精液的最早年龄。我们报告说，在电容期间，ATP1A4在精子中合成。在此提案中，我们将研究潜在的分子机制（目标3）。在这项研究中产生的新知识将对男性生育能力产生很大影响。总体而言，这些研究将创造新的知识，并在跨学科水平上进行重要应用，并对全球粮食生产产生很大影响。我建议培训3名博士生学员和5名夏季学生，为各种职业做准备。