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

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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.