Sperm chemotaxis is a form of sperm guidance, in which sperm cells (spermatozoa) follow a concentration gradient of a chemoattractant secreted from the oocyte and thereby reach the oocyte.
Background Since the discovery of sperm attraction to the female gametes in ferns over a century ago,Pfeffer, W. (1884) Lokomotorische richtungsbewegungen durch chemische reize. Untersuch. aus d. Botan. Inst. Tübingen 1, 363–482. sperm guidance in the form of sperm chemotaxis has been established in a large variety of speciesMiller, R.L. (1985) Sperm chemo-orientation in the metazoa. In: Biology of Fertilization (Metz, C.B. and Monroy, A., eds.), pp. 275–337. Academic Press, New York. Although sperm chemotaxis is prevalent throughout the Metazoa kingdom, ranging from humans to marine species with external fertilization, such as sea urchins and corals,Cosson, M.P. (1990) Sperm chemotaxis. In: Controls of Sperm Motility: Biological and Clinical Aspects (Gagnon, C., ed.) pp. 103–135. CRC Press, Boca Raton, FL.Eisenbach, M. and Tur-Kaspa, I. (1994) Human sperm chemotaxis is not enigmatic anymore. Fertil. Steril. 62, 233–235. much of the current information on sperm chemotaxis is derived from studies of marine invertebrates, primarily sea urchin and starfish.Kaupp, U.B., Kashikar, N.D. and Weyand, I. (2008) Mechanisms of sperm chemotaxis Annu. Rev. Physiol. 70, 93-117. As a matter of fact, until not too long ago, the dogma was that, in mammals, guidance of spermatozoa to the oocyte was unnecessary. This was due to the common belief that, following ejaculation into the female genital tract, large numbers of spermatozoa 'race' towards the oocyte and compete to fertilize it.
Research during the 1980s"Professor Michael Eisenbach of the Weizmann Membrane Research Department was inspired to initiate this research several years ago when ..." caused this belief to be taken apart when it became clear that only few of the ejaculated spermatozoa — in humans, only ~1 of every million spermatozoa — succeed in entering the oviducts (fallopian tubes)Eisenbach, M. and Giojalas, L.C. (2006) Sperm guidance in mammals - an unpaved road to the egg. Nat. Rev. Mol. Cell Biol. 7, 276–285. and when more recent studies showed that mammalian spermatozoa do respond chemotactically.Ralt, D., Manor, M., Cohen-Dayag, A., Tur-Kaspa, I., Makler, A., Yuli, I., Dor, J., Blumberg, S., Mashiach, S. and Eisenbach, M. (1994) Chemotaxis and chemokinesis of human spermatozoa to follicular factors. Biol. Reprod. 50, 774–785.
Sperm chemotaxis in non-mammalian species
In sperm chemotaxis, the oocyte secretes a chemoattractant, which, as it diffuses away, forms a concentration gradient: a high concentration close to the egg, and a gradually lower concentration as the distance from the oocyte increases. Spermatozoa can sense this chemoattractant and orient their swimming direction up the concentration gradient towards the oocyte. Sperm chemotaxis was demonstrated in a large number of non-mammalian species, from marine invertebrates to frogs.Al-Anzi, B. and Chandler, D.E. (1998) A sperm chemoattractant is released from Xenopus egg jelly during spawning. Dev. Biol. 198, 366–375.
Chemoattractants
The sperm chemoattractants in non-mammalian species vary to a large extent. Some examples are shown in Table 1. So far, most sperm chemoattractants that have been identified in non-mammalian species are peptides or low-molecular-weight proteins (1–20 kDa), which are heat stable and sensitive to proteases. Exceptions to this rule are the sperm chemoattractants of corals, ascidians, plants such as ferns, and algae (Table 1).
Table 1. Some sperm chemoattractants in non-mammalian species*
Species Chemoattractant References Algae Low-molecular-weight unsaturated pheromones of cyclic or linear structure (for example 532 Da pentosylated hydroquinone in the case of Chlamydomonas allensworthii) Maier, I. and Müller, D.G. (1986) Sexual pheromones in algae. Biol. Bull. 170, 145–175.Starr, R.C., Marner, F.J. and Jaenicke, L. (1995) Chemoattraction of male gametes by a pheromone produced by female gametes of chlamydomonas. Proc. Natl. Acad. Sci. U.S.A. 92, 641–645. Amphibians Allurin — a 21 kDa protein (for Xenopus) Olson, J.H., Xiang, X.Y., Ziegert, T., Kittelson, A., Rawls, A., Bieber, A.L. and Chandler, D.E. (2001) Allurin, a 21-kDa sperm chemoattractant from Xenopus egg jelly, is related to mammalian sperm-binding proteins. Proc. Natl. Acad. Sci. U.S.A. 98, 11205–11210. Ascidians SAAF — a sulfated steroid: 3,4,7,26-tetrahydroxycholestane-3,26-disulfate (for Ciona savignyi and intestinalis) Yoshida, M., Inaba, K. and Morisawa, M. (1993) Sperm chemotaxis during the process of fertilization in the ascidians Ciona-Savignyi and Ciona-Intestinalis. Dev. Biol. 157, 497–506.Yoshida, M., Inaba, K., Ishida, K. and Morisawa, M. (1994) Calcium and cyclic AMP mediate sperm activation, but Ca2+ alone contributes sperm chemotaxis in the ascidian, Ciona savignyi. Dev. Growth Dif. 36, 589–595.Yoshida, M., Murata, M., Inaba, K. and Morisawa, M. (2002) A chemoattractant for ascidian spermatozoa is a sulfated steroid. Proc. Natl. Acad. Sci. U.S.A. 99, 14831–14836. Corals A lipid-like long chain fatty alcohol CH3-(CH2)8-CH=CH-CH=CH-CH2OH (for Montipora digitata) Coll, J.C. and Miller, R.L. (1992) The nature of sperm chemo-attractants in coral and starfis. In: Comparative Spermatology: 20 Years After (Baccetti, B., ed.) pp. 129–134. Raven Press, New York. Ferns Dicarboxylic acids, for example malic acid in its partially ionized form (for Pteridium aquilinum) Brokaw, C.J. (1958) Chemotaxis of bracken spermatozoids. The role of bimalate ions. J. Exp. Zool. 35, 192–196. Mollusks SepSAP — a 6-residue peptide-amide with the sequence PIDPGV-CONH2 (for Sepia officinalis) Zatylny, C., Marvin, L., Gagnon, J. and Henry, J.L. (2002) Fertilization in Sepia officinalis: the first mollusk sperm-attracting peptide. Biochem. Biophys. Res. Commun. 296, 1186–1193. Sea urchins Resact — a 14-residue peptide with the sequence CVTGAPGCVGGGRL-NH2 (for Arbacia punctulata) Ward, G.E., Brokaw, C.J., Garbers, D.L. and Vacquier, V.D. (1985) Chemotaxis of Arbacia punctulata spermatozoa to resact, a peptide from the egg jelly layer. J. Cell Biol. 101, 2324–2329. Starfish Startrak — a 13 kDa heat-stable protein (for Pycnopodia helianthoides) Miller, R.D. and Vogt, R. (1996) An N-terminal partial sequence of the 13kDa Pycnopodia helianthoides sperm chemoattractant 'startrak' possesses sperm-attracting activity. J. Exp. Biol. 199, 311–318.
Taken from reference.Eisenbach, M. (2004) Chemotaxis. Imperial College Press, London.
Species specificity
The variety of chemoattractants raises the question of species specificity with respect to the chemoattractant identity. There is no single rule for chemoattractant-related specificity. Thus, in some groups of marine invertebrates (e.g., hydromedusae and certain ophiuroids), the specificity is very high; in others (e.g., starfish), the specificity is at the family level and, within the family, there is no specificity.Miller, R.L. (1997) Specificity of sperm chemotaxis among great barrier reef shallow-water holothurians and ophiuroids. J. Exp. Zool. 279, 189–200. In mollusks, there appears to be no specificity at all. Likewise, in plants, a unique simple compound [e.g., fucoserratene — a linear, unsaturated alkene (1,3-trans 5-cis-octatriene)] might be a chemoattractant for various species.
Behavioral mechanism Here, too, there is no single rule. In some species (for example, in hydroids like Campanularia or tunicate like Ciona), the swimming direction of the spermatozoa changes abruptly towards the chemoattractant source. In others (for example, in sea urchin, hydromedusa, fern, or fish such as Japanese bitterlings), the approach to the chemoattractant source is indirect and the movement is by repetitive loops of small radii. In some species (for example, herring or the ascidian Ciona) activation of motility precedes chemotaxis.Kaupp, U.B., Hildebrand, E. and Weyand, I. (2006) Sperm chemotaxis in marine invertebrates - molecules and mechanism. J. Cell. Physiol. 208, 487–494.Morisawa, M. (1994). Cell signaling mechanisms for sperm motility. Zool. Sci. 11, 647–662. In chemotaxis, cells may either sense a temporal gradient of the chemoattractant, comparing the occupancy of its receptors at different time points (as do bacteriaMacnab, R.M. and Koshland, D.E. (1972) The gradient-sensing mechanism in bacterial chemotaxis. Proc. Natl. Acad. Sci. U.S.A. 69, 2509–2512.), or they may detect a spatial gradient, comparing the occupancy of receptors at different locations along the cell (as do leukocytesDevreotes, P.N. and Zigmond, S.H. (1988) Chemotaxis in eukaryotic cells: a focus on leukocytes and Dictyostelium. Annu Rev Cell Biol 4, 649–86.). In the best-studied species, sea urchin, the spermatozoa sense a temporal gradient and respond to it with a transient increase in flagellar asymmetry. The outcome is a turn in the swimming path, followed by a period of straight swimming,Kaupp, U.B., Solzin, J., Hildebrand, E., Brown, J.E., Helbig, A., Hagen, V., Beyermann, M., Pampaloni, F. and Weyand, I. (2003) The signal flow and motor response controlling chemotaxis of sea urchin sperm. Nature Cell Biol. 5, 109–117. leading to the observed epicycloid-like movements directed towards the chemoattractant source.Böhmer, M., Van, Q., Weyand, I., Hagen, V., Beyermann, M., Matsumoto, M., Hoshi, M., Hildebrand, E. and Kaupp, U.B. (2005) Ca2+ spikes in the flagellum control chemotactic behavior of sperm. EMBO J. 24, 2741–2752. The particular mechanism by which sea urchin sperm cells sense the temporal gradient has been recently identified as a natural implementation of the well-known adaptive controller known as extremum seeking. Abdelgalil, M., Aboelkassem, Y., Taha, H. (2022) Sea urchin sperm exploit extremum seeking control to find the egg. Phys. Rev. E 106, L062401
Molecular mechanism
The molecular mechanism of sperm chemotaxis is still not fully known. The current knowledge is mainly based on studies in the sea urchin Arbacia punctulata, where binding of the chemoattractant resact (Table 1) to its receptor, a guanylyl cyclase, activates cGMP synthesis (Figure 1). The resulting rise of cGMP possibly activates K+-selective ion channels. The consequential hyperpolarization activates hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels. The depolarizing inward current through HCN channels possibly activates voltage-activated Ca2+ channels, resulting in elevation of intracellular Ca2+. This rise leads to flagellar asymmetry and, consequently, a turn of the sperm cell.
A model of the signal-transduction pathway during sperm chemotaxis of the sea urchin Arbacia punctulata. Binding of a chemoattractant (ligand) to the receptor — a membrane-bound guanylyl cyclase (GC) — activates the synthesis of cGMP from GTP. Cyclic GMP possibly opens cyclic nucleotide-gated (CNG) K+-selective channels, thereby causing hyperpolarization of the membrane. The cGMP signal is terminated by the hydrolysis of cGMP through phosphodiesterase (PDE) activity and inactivation of GC. On hyperpolarization, hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels allow the influx of Na+ that leads to depolarization and thereby causes a rapid Ca2+ entry through voltage-activated Ca2+ channels (Cav), Ca2+ ions interact by unknown mechanisms with the axoneme of the flagellum and cause an increase of the asymmetry of flagellar beat and eventually a turn or bend in the swimming trajectory. Ca2+ is removed from the flagellum by a Na+/Ca2+ exchange mechanism. (Taken from ref.)
Sperm chemotaxis in mammals