Sperm guidance
Encyclopedia
Sperm guidance is the process by which sperm
cells (spermatozoa) are directed to the oocyte
(egg) for the aim of fertilization. In the case of marine invertebrates the guidance is done by chemotaxis
. In the case of mammals, it appears to be done by both chemotaxis and thermotaxis
.
over a century ago (Pfeffer, 1884), sperm guidance in the form of sperm chemotaxis has been established in a large variety of species (Miller, 1985). Although sperm chemotaxis is prevalent throughout the Metazoa kingdom, from marine species with external fertilization such as sea urchins and corals, to humans (Cosson, 1990; Eisenbach and Tur-Kaspa, 1994; Miller, 1985), most of the current information on sperm chemotaxis is derived from studies of marine invertebrates, primarily sea urchin and starfish (Kaupp et al., 2006). 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. This belief was 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 and Tur-Kaspa (1999) for a review], and when more recent studies showed that mammalian spermatozoa employ two different guidance mechanisms: chemotaxis (Ralt et al., 1994) and thermotaxis (Bahat et al., 2003).
), which are heat stable and sensitive to proteases (Cosson, 1990; Miller, 1985). Exceptions to this rule are the sperm chemoattractants of corals, ascidians, plants such as ferns, and algae
(Table 1).
(1,3-trans 5-cis-octatriene)] might be a chemoattractant for various species (Maier and Müller, 1986).
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 (Cosson, 1990; Kaupp et al., 2006; Miller, 1985; Morisawa, 1994).
In chemotaxis, cells may either sense a temporal gradient of the chemoattractant, comparing the occupancy of its receptors at different time points [as do bacteria
(Macnab and Koshland, 1972)], or they may detect a spatial gradient, comparing the occupancy of receptors at different locations along the cell [as do leukocytes (Devreotes and Zigmond, 1988)]. In the best-studied species, sea urchin, the spermatozoa sense a temporal gradient (Kaupp et al., 2003) 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 et al., 2003), leading to the observed epicycloid-like movements directed towards the chemoattractant source (Böhmer et al., 2005).
, 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, to a turn of the sperm cell (Kaupp et al., 2006).
Figure 1. 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 (Kaupp et al., 2006).]
(Ralt et al., 1991; Villanueva-Díaz et al., 1990) and that there is a remarkable correlation between this in vitro accumulation and oocyte fertilization (Ralt et al., 1991), chemotaxis was substantiated as the cause of this accumulation (Ralt et al., 1994). Sperm chemotaxis was later also demonstrated in mice (Giojalas and Rovasio, 1998; Oliveira et al., 1999) and rabbits (Fabro et al., 2002). In addition, sperm accumulation in follicular fluid (but without substantiating that it truly reflects chemotaxis) was demonstrated in horses (Navarro et al., 1998) and pigs (Serrano et al., 2001).
A key feature of sperm chemotaxis in humans is that this process is restricted to capacitated
cells (Cohen-Dayag et al., 1995; Eisenbach, 1999) — the only cells that possess the ability to penetrate the oocyte and fertilize it (Jaiswal and Eisenbach, 2002). This raised the possibility that, in mammals, chemotaxis is not solely a guidance mechanism but it is also a mechanism of sperm selection (Cohen-Dayag et al., 1995; Eisenbach, 1999). Importantly, the fraction of capacitated (and, hence, chemotactically responsive) spermatozoa is low (~10% in humans), the life span of the capacitated/chemotactic state is short (1–4 hours in humans), a spermatozoon can be at this state only once in its lifetime, and sperm individuals become capacitated/chemotactic at different time points, resulting in continuous replacement of capacitated/chemotactic cells within the sperm population, i.e., prolonged availability of capacitated cells (Cohen-Dayag et al., 1994; 1995). These sperm features raised the possibility that prolonging the time period, during which capacitated spermatozoa can be found in the female genital tract, is a mechanism, evolved in humans, to compensate for the lack of coordination between insemination and ovulation (Cohen-Dayag et al., 1995; Eisenbach, 1999; Eisenbach and Giojalas, 2006; Giojalas et al., 2004).
(Guidobaldi et al., 2008; Oren-Benaroya et al., 2008; Teves et al., 2006). Additional sperm chemoattractants have been found, examples are atrial natriuretic peptide
(ANP) (Zamir et al., 1993) and specific odorants (Spehr et al., 2003) [complete chemoattractant lists can be found in (Eisenbach, 2004; Eisenbach and Giojalas, 2006)], but it is an open question whether they are physiologically involved in guidance in vivo.
(Spehr et al., 2003) suggest that mammalian sperm chemotaxis involves a signal transduction pathway similar to that of the olfactory system. This may seem a valid possibility in view of the finding that male germ cells appear to contain all the elements of the signaling cascade present in olfactory cells (Defer et al., 1998) and the observation that bourgeonal induces a transient Ca2+ influx in about one third of the cells of human spermatozoa, a response that is inhibited by an adenylyl cyclase inhibitor (Spehr et al., 2003; Spehr et al., 2004). It is possible that mammalian spermatozoa possess both signal-transduction systems. The observation that intracellular photorelease of each cAMP and cGMP causes a similar behavioral response (Gakamsky et al., 2009) is consistent with this possibility.
-oviduct junction, a drop that occurs in spite of the simultaneous rise in body temperature at ovulation
(Bahat et al., 2005). Following the suggestion of Hunter (1998) that this temperature difference might serve as a cue for guiding spermatozoa to the site of fertilization, Bahat et al. (2003) demonstrated that rabbit and human spermatozoa are able to sense small temperature differences and respond to them by thermotaxis. The temperature gradient in the rabbit oviduct was calculated to be at the order of 0.1°C/cm (Bahat and Eisenbach, 2006), within the range of known thermotaxis
systems. As in sperm chemotaxis, only capacitated spermatozoa are thermotactically responsive (Bahat et al., 2003).
The findings that mammalian spermatozoa are capable to respond to a chemoattractant gradient by chemotaxis and to a temperature gradient by thermotaxis and that both such gradients are established in the female genital tract raised the possibility that spermatozoa guidance is done by both chemotaxis and thermotaxis. It was further suggested that, in vivo, each mechanism is functional in a region of the oviduct where the other mechanism is ineffective (Bahat et al., 2003; Eisenbach and Giojalas, 2006). According to this suggestion (Figure 2), capacitated spermatozoa, released from the sperm storage site at the isthmus
(Suarez, 2002), may be first guided by thermotaxis from the cooler sperm storage site towards the warmer fertilization site (Bahat et al., 2003). Passive contractions of the oviduct (Battalia and Yanagimachi, 1979) may assist the spermatozoa to reach there. At this location the spermatozoa may be chemotactically guided to the oocyte-cumulus complex by the gradient of progesterone, secreted from the cumulus cells. In addition, progesterone may inwardly guide spermatozoa, already present within the periphery of the cumulus oophorus (Teves et al., 2006). Spermatozoa that are already deep within the cumulus oophorus may sense the more potent chemoattractant that is secreted from the oocyte (Sun et al., 2005) and chemotactically guide themselves to the oocyte according to the gradient of this chemoattractant. It should be borne in mind, however, that this is only a model. In view of the increasing number of different chemoattractants that are being discovered, the guidance in vivo might be much more complex.
Figure 2. A simplified scheme describing the suggested sequence of sperm guidance events in mammals.
Sperm
The term sperm is derived from the Greek word sperma and refers to the male reproductive cells. In the types of sexual reproduction known as anisogamy and oogamy, there is a marked difference in the size of the gametes with the smaller one being termed the "male" or sperm cell...
cells (spermatozoa) are directed to the oocyte
Oocyte
An oocyte, ovocyte, or rarely ocyte, is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in the ovary during female gametogenesis. The female germ cells produce a primordial germ cell which undergoes a mitotic...
(egg) for the aim of fertilization. In the case of marine invertebrates the guidance is done by chemotaxis
Chemotaxis
Chemotaxis is the phenomenon in which somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming towards the highest concentration of food molecules,...
. In the case of mammals, it appears to be done by both chemotaxis and thermotaxis
Thermotaxis
Thermotaxis is a behavior in which an organism directs its locomotion up or down a gradient of temperature.Lab research has determined that some slime molds and small nematodes can migrate along amazingly shallow temperature gradients of less than 0.1C/cm...
.
Background
Since the discovery of sperm attraction to the female gametes in fernsFern
A fern is any one of a group of about 12,000 species of plants belonging to the botanical group known as Pteridophyta. Unlike mosses, they have xylem and phloem . They have stems, leaves, and roots like other vascular plants...
over a century ago (Pfeffer, 1884), sperm guidance in the form of sperm chemotaxis has been established in a large variety of species (Miller, 1985). Although sperm chemotaxis is prevalent throughout the Metazoa kingdom, from marine species with external fertilization such as sea urchins and corals, to humans (Cosson, 1990; Eisenbach and Tur-Kaspa, 1994; Miller, 1985), most of the current information on sperm chemotaxis is derived from studies of marine invertebrates, primarily sea urchin and starfish (Kaupp et al., 2006). 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. This belief was 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 and Tur-Kaspa (1999) for a review], and when more recent studies showed that mammalian spermatozoa employ two different guidance mechanisms: chemotaxis (Ralt et al., 1994) and thermotaxis (Bahat et al., 2003).
Sperm guidance in non-mammalian species
Sperm guidance in non-mammalian species is performed by 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 is longer. 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 (Cosson, 1990; Miller, 1985) to frogs (Al-Anzi and Chandler, 1998).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 kDaAtomic mass unit
The unified atomic mass unit or dalton is a unit that is used for indicating mass on an atomic or molecular scale. It is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of...
), which are heat stable and sensitive to proteases (Cosson, 1990; Miller, 1985). Exceptions to this rule are the sperm chemoattractants of corals, ascidians, plants such as ferns, and algae
Algae
Algae are a large and diverse group of simple, typically autotrophic organisms, ranging from unicellular to multicellular forms, such as the giant kelps that grow to 65 meters in length. They are photosynthetic like plants, and "simple" because their tissues are not organized into the many...
(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 Chlamydomonas Chlamydomonas is a genus of green algae. They are unicellular flagellates. Chlamydomonas is used as a model organism for molecular biology, especially studies of flagellar motility and chloroplast dynamics, biogenesis, and genetics... allensworthii) |
(Cosson, 1990; Maier and Müller, 1986; Starr et al., 1995) |
| Amphibians | Allurin — a 21 kDa protein (for Xenopus Xenopus Xenopus is a genus of highly aquatic frogs native to Sub-Saharan Africa. There are 19 species in the Xenopus genus... ) |
(Al-Anzi and Chandler, 1998; Olson et al., 2001) |
| Ascidians | SAAF — a sulfated steroid: 3,4,7,26-tetrahydroxycholestane-3,26-disulfate (for Ciona Ciona Ciona is a genus of Cionidae sea squirts.The body of Ciona is bag-like and covered by a tunic, which is a secretion of the epidermal cells. The body is attached at a permanent base located at the posterior part, and the opposite bears two openings, the buccal and atrial siphons... savignyi and intestinalis) |
(Yoshida et al., 1993; 1994; 2002) |
| Corals | A lipid-like long chain fatty alcohol CH3-(CH2)8-CH=CH-CH=CH-CH2OH (for Montipora Montipora Montipora is a genus of small polyp stony coral in the phylum Cnidaria. Depending on the species and location, Montipora may grow as plates or ridges, appearing to some as a bowl or flower. Undisturbed, the plates expand radially and may encrust over surrounding rocks, shells or debris... digitata) |
(Coll and Miller, 1992) |
| Ferns | Dicarboxylic acids, for example malic acid in its partially ionized form (for Pteridium aquilinum Pteridium aquilinum Pteridium aquilinum is a species of fern occurring in temperate and subtropical regions throughout much of the northern hemisphere.... ) |
(Brokaw, 1958) |
| Mollusks | SepSAP — a 6-residue peptide-amide with the sequence PIDPGV-CONH2 (for Sepia Sepia -Marine life:* Sepia , a genus of cuttlefish* Cephalopod ink, a dark pigment released into water by Sepia cuttlefish-Media and entertainment:* Sepia , an African Americans focused Photojournalism magazine... officinalis) |
(Zatylny et al., 2002) |
| Sea urchins | Resact — a 14-residue peptide with the sequence CVTGAPGCVGGGRL-NH2 (for Arbacia punctulata Arbacia punctulata Arbacia punctulata is a species of Arbacia genus of purple-spined sea urchins. Its natural habitat is in the Western Atlantic Ocean. Arbacia punctulata can be found in shallow water from Massachusetts to Cuba and the Yucatan Peninsula, from Texas to Florida in the Gulf of Mexico, the coast from... ) |
(Ward et al., 1985) |
| Starfish | Startrak — a 13 kDa heat-stable protein (for Pycnopodia helianthoides) | (Miller and Vogt, 1996) |
- Taken from (Eisenbach, 2004).
Species specificity
The variety of chemoattractants raises the question of species specificity with respect to the identity of chemoattractant. 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 (Cosson, 1990; Miller, 1985, 1997). In mollusks, there appears to be no specificity at all. Likewise, in plants, a unique simple compound [e.g., fucoserratene — a linear, unsaturated alkeneAlkene
In organic chemistry, an alkene, olefin, or olefine is an unsaturated chemical compound containing at least one carbon-to-carbon double bond...
(1,3-trans 5-cis-octatriene)] might be a chemoattractant for various species (Maier and Müller, 1986).
Behavioral mechanism
Here, too, there is no single rule. In some species (for example, in hydroids like Campanularia or tunicateTunicate
Tunicates, also known as urochordates, are members of the subphylum Tunicata, previously known as Urochordata, a group of underwater saclike filter feeders with incurrent and excurrent siphons that is classified within the phylum Chordata. While most tunicates live on the ocean floor, others such...
like Ciona
Ciona
Ciona is a genus of Cionidae sea squirts.The body of Ciona is bag-like and covered by a tunic, which is a secretion of the epidermal cells. The body is attached at a permanent base located at the posterior part, and the opposite bears two openings, the buccal and atrial siphons...
), 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
Herring
Herring is an oily fish of the genus Clupea, found in the shallow, temperate waters of the North Pacific and the North Atlantic oceans, including the Baltic Sea. Three species of Clupea are recognized. The main taxa, the Atlantic herring and the Pacific herring may each be divided into subspecies...
or the ascidian Ciona) activation of motility precedes chemotaxis (Cosson, 1990; Kaupp et al., 2006; Miller, 1985; Morisawa, 1994).
In chemotaxis, cells may either sense a temporal gradient of the chemoattractant, comparing the occupancy of its receptors at different time points [as do bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
(Macnab and Koshland, 1972)], or they may detect a spatial gradient, comparing the occupancy of receptors at different locations along the cell [as do leukocytes (Devreotes and Zigmond, 1988)]. In the best-studied species, sea urchin, the spermatozoa sense a temporal gradient (Kaupp et al., 2003) and respond to it with a transient increase in flagellar
Flagellum
A flagellum is a tail-like projection that protrudes from the cell body of certain prokaryotic and eukaryotic cells, and plays the dual role of locomotion and sense organ, being sensitive to chemicals and temperatures outside the cell. There are some notable differences between prokaryotic and...
asymmetry. The outcome is a turn in the swimming path, followed by a period of straight swimming (Kaupp et al., 2003), leading to the observed epicycloid-like movements directed towards the chemoattractant source (Böhmer et al., 2005).
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 punctulataArbacia punctulata
Arbacia punctulata is a species of Arbacia genus of purple-spined sea urchins. Its natural habitat is in the Western Atlantic Ocean. Arbacia punctulata can be found in shallow water from Massachusetts to Cuba and the Yucatan Peninsula, from Texas to Florida in the Gulf of Mexico, the coast from...
, where binding of the chemoattractant resact (Table 1) to its receptor, a guanylyl cyclase, activates cGMP
Cyclic guanosine monophosphate
Cyclic guanosine monophosphate is a cyclic nucleotide derived from guanosine triphosphate . cGMP acts as a second messenger much like cyclic AMP...
synthesis (Figure 1). The resulting rise of cGMP possibly activates K+-selective ion channels. The consequential hyperpolarization
Hyperpolarization (biology)
Hyperpolarization is a change in a cell's membrane potential that makes it more negative. It is the opposite of a depolarization.Hyperpolarization is often caused by efflux of K+ through K+ channels, or influx of Cl– through Cl– channels. On the other hand, influx of cations, e.g...
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, to a turn of the sperm cell (Kaupp et al., 2006).
Sperm guidance in mammals: I. Chemotaxis
Following the findings that human spermatozoa accumulate in follicular fluidFollicular fluid
Follicular fluid is a liquid which fills the follicular antrum and surrounds the ovum in an ovarian follicle. This fluid is rich in hyaluronic acid.-External links:* *...
(Ralt et al., 1991; Villanueva-Díaz et al., 1990) and that there is a remarkable correlation between this in vitro accumulation and oocyte fertilization (Ralt et al., 1991), chemotaxis was substantiated as the cause of this accumulation (Ralt et al., 1994). Sperm chemotaxis was later also demonstrated in mice (Giojalas and Rovasio, 1998; Oliveira et al., 1999) and rabbits (Fabro et al., 2002). In addition, sperm accumulation in follicular fluid (but without substantiating that it truly reflects chemotaxis) was demonstrated in horses (Navarro et al., 1998) and pigs (Serrano et al., 2001).
A key feature of sperm chemotaxis in humans is that this process is restricted to capacitated
Capacitation
Capacitation is the penultimate step in the maturation of mammalian spermatozoa and is required to render them competent to fertilize an oocyte.This step is a biochemical event; the sperm move normally and look mature prior to capacitation....
cells (Cohen-Dayag et al., 1995; Eisenbach, 1999) — the only cells that possess the ability to penetrate the oocyte and fertilize it (Jaiswal and Eisenbach, 2002). This raised the possibility that, in mammals, chemotaxis is not solely a guidance mechanism but it is also a mechanism of sperm selection (Cohen-Dayag et al., 1995; Eisenbach, 1999). Importantly, the fraction of capacitated (and, hence, chemotactically responsive) spermatozoa is low (~10% in humans), the life span of the capacitated/chemotactic state is short (1–4 hours in humans), a spermatozoon can be at this state only once in its lifetime, and sperm individuals become capacitated/chemotactic at different time points, resulting in continuous replacement of capacitated/chemotactic cells within the sperm population, i.e., prolonged availability of capacitated cells (Cohen-Dayag et al., 1994; 1995). These sperm features raised the possibility that prolonging the time period, during which capacitated spermatozoa can be found in the female genital tract, is a mechanism, evolved in humans, to compensate for the lack of coordination between insemination and ovulation (Cohen-Dayag et al., 1995; Eisenbach, 1999; Eisenbach and Giojalas, 2006; Giojalas et al., 2004).
Chemoattractants
In humans, there are at least two different origins of sperm chemoattractants. One is the mature oocyte, and the other is the cumulus cells that surround the oocyte (Sun et al., 2005). The identity of the chemoattractant secreted from the oocyte is not known; the one secreted from the cumulus cells is the steroid progesteroneProgesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
(Guidobaldi et al., 2008; Oren-Benaroya et al., 2008; Teves et al., 2006). Additional sperm chemoattractants have been found, examples are atrial natriuretic peptide
Atrial natriuretic peptide
Atrial natriuretic peptide , atrial natriuretic factor , atrial natriuretic hormone , or atriopeptin, is a powerful vasodilator, and a protein hormone secreted by heart muscle cells. It is involved in the homeostatic control of body water, sodium, potassium and fat...
(ANP) (Zamir et al., 1993) and specific odorants (Spehr et al., 2003) [complete chemoattractant lists can be found in (Eisenbach, 2004; Eisenbach and Giojalas, 2006)], but it is an open question whether they are physiologically involved in guidance in vivo.
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 (Sun et al., 2003). The subsequent findings that cumulus cells of both human and rabbit (and, probably, of other mammals as well) secrete the chemoattractant progesterone (Guidobaldi et al., 2008; Oren-Benaroya et al., 2008; Teves et al., 2006) 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 a temporal chemoattractant gradient. This is because the establishment of a temporal gradient in the absence of spatial gradient, achieved by mixing human spermatozoa with a chemoattractant, results in a delayed transient increase in swimming velocity and lateral head displacement, leading to a delayed transient decrease in the linearity of swimming (Gakamsky et al., 2009). When the chemoattractant concentration is high, the spermatozoa exhibit hyperactivated motility. Likewise, photorelease of cyclic nucleotides, considered as putative second messengers of the chemotactic pathway(s) (Kaupp et al., 2003; Spehr et al., 2004), from their caged compounds cause a delayed decrease in the linearity of swimming (Gakamsky et al., 2009), similar to that observed upon the photorelease of progesterone (Kilic et al., 2009). On the basis of these observations it was suggested that the response characteristics observed in temporal gradients also occur in spatial gradients: an excitation phase, composed of a delay (i.e., no change in the motility parameters) and a subsequent turn, and an adaptation phase during which the cell ceases to respond to the chemoattractant even though it is still present. When a spermatozoon swims up a spatial gradient, the turning step is repressed. When it swims down a gradient or in no gradient, the cell turns. In the latter case, if not re-stimulated, the cell eventually adapts and resumes its original swimming mode (Gakamsky et al., 2009).Molecular mechanism
Very little is known on the molecular mechanism of sperm chemotaxis in mammals. It is even not known whether it is similar to that of sea-urchin spermatozoa because, on the one hand, assuming universality — the molecular mechanisms may be similar. The finding in human spermatozoa that ANP, a known activator of particulate guanylyl cyclase, is chemotactically active and the consequent suggestion that ANP may directly affect guanylyl cyclase in a manner similar to that caused by the physiological attractant (Zamir et al., 1993) are in line with this possibility. On the other hand, the identification of the odorant receptor hOR17-4 on human spermatozoa and the demonstration of sperm chemotaxis to its agonist bourgeonalBourgeonal
Bourgeonal is an aromatic aldehyde used in perfumery. It has a fragrance reminiscent of Lily of the Valley, otherwise described as floral, watery, green and aldehydic...
(Spehr et al., 2003) suggest that mammalian sperm chemotaxis involves a signal transduction pathway similar to that of the olfactory system. This may seem a valid possibility in view of the finding that male germ cells appear to contain all the elements of the signaling cascade present in olfactory cells (Defer et al., 1998) and the observation that bourgeonal induces a transient Ca2+ influx in about one third of the cells of human spermatozoa, a response that is inhibited by an adenylyl cyclase inhibitor (Spehr et al., 2003; Spehr et al., 2004). It is possible that mammalian spermatozoa possess both signal-transduction systems. The observation that intracellular photorelease of each cAMP and cGMP causes a similar behavioral response (Gakamsky et al., 2009) is consistent with this possibility.
Sperm guidance in mammals: II. Thermotaxis
At ovulation, at least in rabbits (Bahat et al., 2005; David et al., 1972) and pigs (Hunter and Nichol, 1986), a temperature difference of 1–2°C is established within the oviduct, the temperature being higher at the fertilization site than at the junction between the uterus and the oviduct, close to the sperm storage site in the oviduct (Suarez, 2002). This difference is formed by a time-dependent temperature drop at the uterusUterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
-oviduct junction, a drop that occurs in spite of the simultaneous rise in body temperature at ovulation
Ovulation
Ovulation is the process in a female's menstrual cycle by which a mature ovarian follicle ruptures and discharges an ovum . Ovulation also occurs in the estrous cycle of other female mammals, which differs in many fundamental ways from the menstrual cycle...
(Bahat et al., 2005). Following the suggestion of Hunter (1998) that this temperature difference might serve as a cue for guiding spermatozoa to the site of fertilization, Bahat et al. (2003) demonstrated that rabbit and human spermatozoa are able to sense small temperature differences and respond to them by thermotaxis. The temperature gradient in the rabbit oviduct was calculated to be at the order of 0.1°C/cm (Bahat and Eisenbach, 2006), within the range of known thermotaxis
Thermotaxis
Thermotaxis is a behavior in which an organism directs its locomotion up or down a gradient of temperature.Lab research has determined that some slime molds and small nematodes can migrate along amazingly shallow temperature gradients of less than 0.1C/cm...
systems. As in sperm chemotaxis, only capacitated spermatozoa are thermotactically responsive (Bahat et al., 2003).
Sperm guidance in mammals: III. Chemotaxis and thermotaxis combined
Isthmus
An isthmus is a narrow strip of land connecting two larger land areas usually with waterforms on either side.Canals are often built through isthmuses where they may be particularly advantageous to create a shortcut for marine transportation...
(Suarez, 2002), may be first guided by thermotaxis from the cooler sperm storage site towards the warmer fertilization site (Bahat et al., 2003). Passive contractions of the oviduct (Battalia and Yanagimachi, 1979) may assist the spermatozoa to reach there. At this location the spermatozoa may be chemotactically guided to the oocyte-cumulus complex by the gradient of progesterone, secreted from the cumulus cells. In addition, progesterone may inwardly guide spermatozoa, already present within the periphery of the cumulus oophorus (Teves et al., 2006). Spermatozoa that are already deep within the cumulus oophorus may sense the more potent chemoattractant that is secreted from the oocyte (Sun et al., 2005) and chemotactically guide themselves to the oocyte according to the gradient of this chemoattractant. It should be borne in mind, however, that this is only a model. In view of the increasing number of different chemoattractants that are being discovered, the guidance in vivo might be much more complex.
Figure 2. A simplified scheme describing the suggested sequence of sperm guidance events in mammals.