which, when secreted from the oocyte, is in complex with a carrier protein Additional compounds have been shown to act as chemoattractants for mammalian spermatozoa. They include the chemokine CCL20, atrial natriuretic peptide (ANP), specific odorants,<ref>Spehr, M., Gisselmann, G., Poplawski, A., Riffell, J.A., Wetzel, C.H., Zimmer, R.K. and Hatt, H. (2003) Identification of a testicular odorant receptor mediating human sperm chemotaxis'. Science 299, 2054–2058.</ref> natriuretic peptide type C (NPPC), and allurin, to mention a few. It is reasonable to assume that not all of them are physiologically relevant. Species specificity Species specificity was not detected in experiments that compared the chemotactic responsiveness of human and rabbit spermatozoa to follicular fluids or egg-conditioned media obtained from human, bovine, and rabbit. The subsequent findings that cumulus cells of both human and rabbit (and, probably, of other mammals as well) secrete the chemoattractant progesterone is sufficient to account for the lack of specificity in the chemotactic response of mammalian spermatozoa. Behavioral mechanism Mammalian spermatozoa, like sea-urchin spermatozoa, appear to sense the chemoattractant gradient temporally (comparing receptor occupancy over time) rather than spatially (comparing receptor occupancy over space). This is because the establishment of a temporal gradient in the absence of spatial gradient, achieved by mixing human spermatozoa with a chemoattractant or by photorelease of a chemoattractant from its caged compound, results in delayed transient changes in swimming behavior that involve increased frequency of turns and hyperactivation events. On the basis of these observations and the finding that the level of hyperactivation events is reduced when chemotactically responsive spermatozoa swim in a spatial chemoattractant gradient it was proposed that turns and hyperactivation events are suppressed when capacitated spermatozoa swim up a chemoattractant gradient, and vice versa when they swim down a gradient. In other words, human spermatozoa approach chemoattractants by modulating the frequency of turns and hyperactivation events, similarly to Escherichia coli bacteria. Molecular mechanism As in non-mammalian species, the end signal in chemotaxis for changing the direction of swimming is Ca2+. The discovery of progesterone as a chemoattractant led to the identification of its receptor on the sperm surface – CatSper, a Ca2+ channel present exclusively in the tail of mammalian spermatozoa.Lishko, P.V., Botchkina, I.L. and Kirichok, Y. (2011) Progesterone activates the principal Ca2+ channel of human sperm. Nature 471, 387–391. (Note, though, that progesterone only stimulates human CatSper but not mouse CatSper. Consistently, sperm chemotaxis to progesterone was not found in mice.)