Michael Eisenbach

Sperm guidance in mammals - an unpaved road to the egg.

Contrary to the prevalent view, there seems to be no competition in the mammalian female genital tract among large numbers of sperm cells that are racing towards the egg. Instead, small numbers of the ejaculated sperm cells enter the Fallopian tube, and these few must be guided to make the remaining long, obstructed way to the egg. Here, we review the mechanisms by which mammalian sperm cells are guided to the egg.

Sperm attraction to a follicular factor(s) correlates with human egg fertilizability.

Spermatozoa normally encounter the egg at the fertilization site (in the Fallopian tube) within 24 hr after ovulation. A considerable fraction of the spermatozoa ejaculated into the female reproductive tract of mammals remains motionless in storage sites until ovulation, when the spermatozoa resume maximal motility and reach the fertilization site within minutes. The nature of the signal for sperm movement is not known, but one possible mechanism is attraction of spermatozoa to a factor(s) released from the egg. We have obtained evidence in favor of such a possibility by showing that human spermatozoa accumulate in follicular fluid in vitro. This accumulation into follicular fluid was higher by 30-260% than that observed with buffer alone and was highly significant (P less than 10(-8)). Not all of the follicular fluids caused sperm accumulation; however, there was a remarkably strong correlation (P less than 0.0001) between the ability of follicular fluid from a particular follicle to cause sperm accumulation and the ability of the egg, obtained from the same follicle, to be fertilized. These findings suggest that attraction may be a key event in the fertilization process and may give an insight into the mechanism underlying early egg-sperm communication.

Thermotaxis of mammalian sperm cells: A potential navigation mechanism in the female genital tract

Thermotaxis of mammalian sperm cells: A potential navigation mechanism in the female genital tract

The sperm chemoattractant secreted from human cumulus cells is progesterone

BACKGROUND Human spermatozoa appear to be guided by chemotaxis to the oocyte in the female genital tract. While one of the sources of sperm chemoattractants is the cumulus cells that surround the oocyte, the identity of the chemoattractant secreted from them is unknown. Progesterone, recognized to be secreted from cumulus cells, was demonstrated, at the pM concentration range, to be a chemoattractant for human spermatozoa. Here, we examined whether this steroid is the cumulus-originated chemoattractant for human spermatozoa. METHODS Human cumulus cells were cultured, and the cultured medium was demonstrated to be chemotactically active. Progesterone was then eliminated from the medium by a specific anti-progesterone antibody, and the residual chemotactic activity was assessed. RESULTS The rate of progesterone secretion from the cells decreased with time. Removal of progesterone from the cumulus-cultured medium resulted in total loss of the chemotactic activity of the medium. Furthermore, the cumulus-cultured medium could substitute for progesterone in stimulating changes in the intracellular Ca(2+) concentration in the spermatozoa, and the changes were very similar to those caused by measured progesterone concentrations in the medium. CONCLUSIONS Taken together, the results suggest that progesterone is the main, if not the sole, chemoattractant secreted by human cumulus cells.

Chemotaxis of Capacitated Rabbit Spermatozoa to Follicular Fluid Revealed by a Novel Directionality-Based Assay

Abstract Precontact communication between gametes is established by chemotaxis. Sperm chemotaxis toward factor(s) in follicular fluid (FF) has been demonstrated in humans and mice. In humans, the chemotactic responsiveness is restricted to capacitated spermatozoa. Here, we investigated whether sperm chemotaxis to factor(s) present in FF also occurs in rabbits and, if so, whether only capacitated spermatozoa are chemotactically responsive. Chemotaxis assays were performed by videomicroscopy in a Zigmond chamber. We measured chemotactic responsiveness as a function of FF dilution by means of a novel directionality-based method that considers the ratio between the distances traveled by the spermatozoa both parallel to the chemoattractant gradient and perpendicular to it. A peak of maximal response was observed at 10−4 dilution of FF, resulting in a typical chemotactic concentration-dependent curve in which 23% of the spermatozoa were chemotactically responsive. In contrast, the percentage of cells exhibiting FF-dependent enhanced speed of swimming increased with the FF concentration, whereas the percentage of cells maintaining linear motility decreased with the FF concentration. The percentages of chemotactically responsive cells were very similar to those of capacitated spermatozoa. Depletion of the latter by stimulation of the acrosome reaction resulted in a total loss of the chemotactic response, whereas the reappearance of capacitated cells resulted in a recovery of chemotactic responsiveness. We conclude that rabbit spermatozoa, like human spermatozoa, are chemotactically responsive to FF factor(s) and acquire this responsiveness as part of the capacitation process.

Mammalian sperm chemotaxis and its association with capacitation

Much progress has been made in recent years in establishing mammalian sperm chemotaxis and understanding sperm capacitation. Thus far, chemotaxis to follicular fluid has been established by a variety of means in human and mouse spermatozoa. It was found that only a small fraction of a given sperm population (averaging around 10%) is chemotactically responsive and that this fraction constitutes capacitated (ripe) spermatozoa. Both the chemotactic responsiveness and the capacitated state are transient (with a lifetime of 50 min to 4 h) and they occur only once in the sperms lifetime. It has been proposed that the role of sperm chemotaxis in mammals (at least in humans) is selective recruitment of capacitated spermatozoa for fertilizing the egg, and that the role of the continuous replacement of chemotactic/capacitated spermatozoa is to prolong the time during which capacitated spermatozoa are available in the female reproductive tract. The sperm chemoattractants have not been identified, but they appear to be heat-stable peptides. Although the molecular mechanism and the in vivo location of sperm chemotaxis are not known, a number of possible mechanisms and locations are discussed.

Do human eggs attract spermatozoa

A key process in human fertilization is bringing the two gametes together, so that the complex molecular events involved in sperm and egg interaction can begin. Does nature allow fertilization to occur only as a consequence of a chance collision, or is there a precontact sperm‐egg communication? This review summarizes the bioassays used in testing human spermatozoa for chemotaxis, emphasizing the necessity to distinguish between chemotaxis and other accumulation‐causing processes, and the results obtained. It demonstrates that human sperm chemotaxis to a follicular factor(s) does occur, at least in vitro, and that only capacitated spermatozoa are chemotactically responsive. Substances that have been proposed as attractants for human spermatozoa are reassessed. The potential role of sperm chemotaxis in vivo is discussed. Faulty precontact sperm‐egg communication may be one of the causes of male infertility, female infertility, or both. On the other hand, interfering with human sperm chemotaxis may represent an exciting new approach to contraception. BioEssays 21:203–210, 1999.

Sperm capacitation is, after all, a prerequisite for both partial and complete acrosome reaction

The acrosome reaction (AR) – an essential step in mammalian fertilization – can occur, according to the consensus, only in capacitated spermatozoa. In apparent contrast, recent reports have demonstrated that human spermatozoa incubated in vitro in an albumin‐free medium and therefore believed to be non‐capacitated, do undergo the AR. With the aim of determining unequivocally whether or not capacitation is required for the AR and whether albumin is essential for capacitation, we compared the potential to undergo partial and complete AR (induced by phorbol myristate ester or by the Ca2+ ionophore A23187) between human spermatozoa incubated in a capacitating medium, albumin‐free medium, and non‐capacitating medium. The results clearly demonstrate that capacitation is, after all, a prerequisite for both partial and complete AR. Albumin, on the other hand, is essential only for acquiring the capacity to undergo complete, not partial AR.

Lack of species-specificity in mammalian sperm chemotaxis

Attraction of spermatozoa by way of chemotaxis to substances secreted from the egg or its surrounding cells has been demonstrated in marine species, amphibians, and mammals. This process is species- or family-specific in marine invertebrates: a chemoattractant for one marine species is usually not recognized by another species or by a member of another family. It is not known whether this selectivity is also the rule in other phyla. Furthermore, it is not at all obvious that such selectivity would be advantageous to species with internal fertilization. Here, using a directionality-based assay for chemotaxis, we studied in vitro the chemotactic response of human and rabbit spermatozoa to human, rabbit, and bovine egg-related factors. We found that spermatozoa from each of the two sources responded similarly well to egg-related factors obtained from any of the three species examined. These results indicate lack of chemotaxis-related, species specificity between these species, suggesting that their sperm chemoattractants are common or very similar. The findings further suggest that mammals do not rely on species specificity of sperm chemotaxis for avoidance of interspecies fertilization.

Behavioral Mechanism during Human Sperm Chemotaxis: Involvement of Hyperactivation

When mammalian spermatozoa become capacitated they acquire, among other activities, chemotactic responsiveness and the ability to exhibit occasional events of hyperactivated motility—a vigorous motility type with large amplitudes of head displacement. Although a number of roles have been proposed for this type of motility, its function is still obscure. Here we provide evidence suggesting that hyperactivation is part of the chemotactic response. By analyzing tracks of spermatozoa swimming in a spatial chemoattractant gradient we demonstrate that, in such a gradient, the level of hyperactivation events is significantly lower than in proper controls. This suggests that upon sensing an increase in the chemoattractant concentration capacitated cells repress their hyperactivation events and thus maintain their course of swimming toward the chemoattractant. Furthermore, in response to a temporal concentration jump achieved by photorelease of the chemoattractant progesterone from its caged form, the responsive cells exhibited a delayed turn, often accompanied by hyperactivation events or an even more intense response in the form of flagellar arrest. This study suggests that the function of hyperactivation is to cause a rather sharp turn during the chemotactic response of capacitated cells so as to assist them to reorient according to the chemoattractant gradient. On the basis of these results a model for the behavior of spermatozoa responding to a spatial chemoattractant gradient is proposed.