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

在不久的将来，全球对粮食的需求将大幅增加。由于牛的繁殖率即使略有提高，也会大大提高肉和奶的产量，因此提高繁殖效率的研究将大大有利于加拿大的养牛业和经济，并对全球粮食生产产生积极影响。在这方面，公牛的生育能力特别重要，因为来自一头良种公牛的数百万份冷冻精液可能用于育种。因此，准确预测这些公牛的生育能力至关重要。传统上根据常规精液评估程序被归类为满意育种者的公牛在生育力方面各不相同。因此，鉴定生育力的分子标记和评价公牛中这些生物标志物的含量变化的遗传基础，将使动物育种家和遗传公司在公牛的早期年龄在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。在我过去的研究中（NSERC DG的支持），我产生了新的知识，钠，钾ATP酶（NKA）参与调节公牛的睾丸和精子功能，并提出ATP 1A4（NKA蛋白家族的一员，只存在于睾丸和精子）作为生育标记。该提案的重点是了解ATP 1A4调节公牛生育力的分子机制。我们将确定这种蛋白在睾丸细胞（支持细胞）的生长和分裂中的作用，这些细胞协调和支持精子发生（目标1）。由于成年睾丸中支持细胞的数量是精液生产潜力的决定因素，我们的研究结果将有助于制定公牛管理策略，以增加支持细胞的数量和繁殖潜力。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）在获能（女性精子的最终成熟使其具有可受精性）期间。然而，这种相互作用的生理意义及其对获能和受精的后果仍然未知，这将在本研究中进行研究（目标2）。这些结果将提高生殖技术的效率，相关的基因检测和选择公牛在他们最早的年龄出售他们的精液。我们报道了ATP 1A4在精子获能过程中的合成。在这个提议中，我们将研究潜在的分子机制（目标3）。这项研究产生的新知识将对男性生育领域产生重大影响。总的来说，这些研究将创造新的知识，在跨学科水平上具有重要的应用，对全球粮食生产产生重大影响。我建议培养3名博士生和5名暑期学生，为他们的各种职业做准备。

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.