The function of cAMP and Ca2+ in motility of human sperm

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Cyclic nucleotides and Ca2+ play key roles in chemotactic signaling of sperm from marine invertebrates. While these messenger molecules have also been invoked in chemotaxis of mammalian sperm, our knowledge is either fragmentary or controversial. We propose here to study the function of cAMP and Ca2+ in motility and chemotaxis of human sperm. Using kinetic techniques and caged compounds, we will examine the motor response evoked by a rapid step increase of either cAMP or Ca2+ in the sperm flagellum. We will study the cAMP response of sperm stimulated with putative chemoattractants and activators of adenylyl cyclases. Furthermore, we will examine the mechanisms by which either putative chemoattractants or cAMP elevate intracellular Ca2+ concentration using fluorescent potentiometric probes and Ca2+ dyes.Our earlier studies demonstrated that mammalian spermatozoa are capable of being guided to the oocyte at the fertilization site by two active processes; chemotaxis and thermotaxis. The molecular mechanisms underlying these processes are obscure. Our aim is to reveal molecular steps in these mechanisms and to determine their sequence. To this end we will apply rapid-mixing techniques to look for changes in the levels of potential second messengers, which occur within the time scale of the swimming response of human spermatozoa to a change in chemoattractant concentration (for chemotaxis) or to a temperature shift (for thermotaxis). We will also try to identify the sperm thermosensors used by the cell for thermotaxis. The information gained is expected to contribute new perspectives to our understanding of mammalian reproduction and to have potential future implications to diagnosing and treating human fertility.