Elucidating the intracellular mechanisms that regulate mammalian sperm fertilizing ability and motility.

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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 interact with the cells and secretions of the female reproductive tract in order to undergo surface and intracellular modifications, named as a whole as capacitation, and 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 Ca2+ intracellular levels and the exact roles of Ca2+ 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 on when spermatozoa will interact with the egg. We will also investigate further the importance of Ca2+ in sperm capacitation. We recently identified numerous proteins that bind to calmodulin, the major intracellular Ca2+ mediator, among which the actin capping protein CapZ alpha 3 and the protein phosphatase PPEF1 were found. Therefore, the involvement of Ca2+, calmodulin, and CapZ alpha will be evaluated in the dynamics of actin polymerization and depolymerization, and determine whether protein tyrosine phosphorylation affects this cellular phenomenon. We will also investigate whether PPEF1 is involved in the regulation of sperm capacitation and motility. The changes in sperm intracellular events elucidated in this research program will undoubtedly lead to a better knowledge on sperm fertilizing ability. This would ultimately have an impact on the 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 production that 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.