Comparative studies on the regulation of metabolism during sperm capacitation

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Summary/Abstract Mammalian sperm acquire fertilization capacity as they transit through the reproductive tract in a process known as capacitation. During capacitation, sperm change their motility pattern and become competent to undergo an acrosome reaction and fertilize an oocyte. These capacitation-associated processes require energy, and sperm are dependent on nutrients in their environment to complete them. Sperm are exposed to different nutrients in their surroundings as they pass from being stored in the cauda epididymis to the fallopian tube where they will meet and fertilize the oocyte. In the previous funding period, we demonstrated that sperm supplied with exogenous glucose generate ATP via glycolysis and oxidative phosphorylation, and glucose utilization via both pathways increases in capacitating sperm. In addition, we found that capacitating sperm alter activity through the pentose phosphate pathway and sperm deprived of exogenous nutrients can metabolize endogenous energy sources. We now propose to apply modern metabolite profiling combined with metabolic flux analyses to identify how sperm coordinately regulate their metabolic pathways and leverage different exogenous nutrients as they mature through distinct activation states. Soluble adenylyl cyclase (sAC) is essential for the molecular changes observed during capacitation, and we will use our unique tools for modulating its activity to test the hypothesis that sAC regulates the metabolic changes induced by capacitation.