Stimulation Of Sperm Motility Research Articles

Pharmacological stimulation of sperm motility

The treatment of male factor infertility is a rapidly developing field. The introduction of microsurgical fertilization techniques allows assisted conception units to treat couples who previously would not have benefited from in-vitro fertilization techniques. However, these techniques are only used for the minority of subfertile men in andrological practice. Many subfertile men are still treated pharmacologically or by sperm selection methods to enhance sperm fertilizing ability. Numerous pharmacological compounds have been described that enhance sperm motility and thus, potentially, sperm fertilizing capacity. This paper attempts to review these compounds and assess their role in treatment of the subfertile male.

Sperm recovery techniques to maximize fertilizing capacity.

Because seminal plasma contains factors that inhibit the fertilizing ability of spermatozoa, it is essential that spermatozoa be separated from it quickly and efficiently. Although the success of a sperm preparation method is often assessed by the yield of motile spermatozoa, the choice of a method also depends on its technical complexity, the materials and apparatus required and time costs. Any exposure of spermatozoa during preparation to factors that may cause iatrogenic sperm dysfunction must obviously be avoided. Consequently, methods involving centrifugal washing prior to the selection of motile spermatozoa should be avoided. Direct swim-up from semen is the simplest way to obtain highly motile sperm populations and can be a very rapid procedure with normal semen samples. Two-layer discontinuous Percoll gradients give excellent yields when the lower layer contains 81% (v/v) Percoll. However, for severely asthenozoospermic cases the results can be disappointing and a Nycodenz gradient may be better, although the 'mini-Percoll' technique might be useful if special care is taken to protect the spermatozoa from damage induced by free radicals. In such cases the migration-sedimentation approach can also be successful. Abnormal samples, especially those with increased viscosity, may benefit from prior dilution with culture medium, or even chymotrypsin-induced liquefaction, before density gradient centrifugation. Finally, pharmacological stimulation of sperm motility may increase yields but, for in vitro fertilization (IVF), such spermatozoa must be used to inseminate oocytes as soon as possible after exposure to the stimulant, although after its removal.

Effect of pentoxifylline on sperm motion.

The ability of pentoxifylline to stimulate sperm motility characteristics was assessed. The effect of pentoxifylline was immediate and lasted for 240 min. The percent motility was increased 1.5-fold when compared with the control at 120, 180, and 240 min after pentoxifylline treatment. Significant increases in velocity and amplitude of lateral head displacement by the agent were observed at 120 min after the start of incubation. Conversely, linearity was reduced by pentoxifylline. Beat-cross frequency did not show any significant change by the agent at any time point. Sperm swelling was not influenced by pentoxifylline throughout the experiment. It would appear that pentoxifylline stimulates sperm motion in vitro with no change of the sperm membrane.

Factors from fluid of the ovarian pocket that stimulate sperm motility in domestic hens.

Fluid was collected from the region of the peritoneum surrounding the ovarian pocket of domestic hens at about the time of ovulation. This fluid, diluted to 10%, increased the motility of chicken spermatozoa by a maximum of sixfold at 40 degrees C in vitro. Gel filtration revealed two peaks of motility-stimulating activity: one was identified as calcium and the other as a heat-labile substance of low M(r) (200). It is suggested that this motility-stimulating activity may facilitate fertilization, as spermatozoa are normally stored in a quiescent state within the oviduct and can be passively transported by cilia to the site of fertilization in the ovarian pocket.

Pentoxifylline stimulates sperm motility

Pentoxifylline stimulates sperm motility

Glucose regulation of guinea-pig sperm motility

Washed guinea-pig spermatozoa from the vas deferens re-acquired progressive motility within 1-2 min of incubation in minimal culture medium containing pyruvate and lactate. When glucose was added, either at the beginning or after 15 min of incubation, the cells showed stimulated motility (increased straight-line velocity, linearity and beat-cross frequency, P less than 0.01). Re-acquisition of progressive motility was preceded by a significant (P less than 0.005) transient increase in sperm concentration of cyclic adenosine 5'-phosphate (cAMP) with or without glucose in the medium. Papaverine caused another large significant (P less than 0.001) increase in cAMP concentration; and 5.56mM glucose with papaverine caused a further stimulation in cAMP beyond that with papaverine alone (P less than 0.005). Although 0.05 or 5.56mM glucose plus alpha-chlorohydrin stimulated sperm motility, they did not further stimulate the increase in cAMP after 30 s of incubation. Thus, there was no apparent correlation between the glucose-stimulating effect on sperm motility and the enhancement of cAMP at 30 s. However, there was a close correlation between glucose-stimulated motility and enhancement of ATP (P less than 0.05) by glucose even under incubation conditions in which glucose caused the Crabtree effect (decrease in respiration rate).

Effects of seminal plasma from normal and asthenozoospermic men on the progressive motility of washed human sperm

Human seminal plasma stimulated the progressive motility of human sperm in a dose- and time-related manner. Serum exhibited a similar capacity for stimulation. Seminal plasma from different normozoospermic men showed marked variation in its capacity to stimulate sperm motility. The stimulatory effect was maintained after heat-treatment, indicating the action of a low molecular weight substance or metal ion. No differences could be observed in the capacity for stimulation between seminal plasma from normozoospermic (n = 23) and asthenozoospermic (n = 22) men, when tested at the same dilution and under identical conditions. It is concluded that in general, differences in seminal plasma composition cannot account for the reduced sperm motility in asthenozoospermic men. Furthermore, the stimulatory effects of seminal plasma may be a property shared by other biological fluids.

Quantitative assessment of the serum‐induced stimulation of human sperm motility

In previous studies, sperm populations with high motility and fertilizing potential have been isolated using Percoll gradients and/or addition of serum or caffeine, but no objective measurements of the motility parameters affected have been presented. In addition, the types of sperm populations and the incidence of positive or negative responses to these treatments have never been documented. In this paper, the proportion of samples responding positively or negatively to these treatments and the type of motility stimulation observed was measured using the CellSoft computer-assisted digital image analysis system. Semen, obtained from the Infertility Clinic, was washed on discontinuous Percoll gradients. Sperm motility parameters were measured in the original semen and after washing through a Percoll gradient in the presence or absence of serum or caffeine. Percoll washing permitted a good recovery of essentially pure sperm. The Percoll treatment had little effect on the percentage of motile sperm but caused a decrease in the linearity-related parameters. A high proportion of the washed sperm samples supplemented with serum showed an increase in at least one of the motility parameters when compared to sperm populations in the original semen (68% of cases) or after Percoll washing (96% of cases). These effects were maintained for several hours. The stimulation of motility was concentration-dependent, with an optimum around 25-30% serum. Caffeine (4 mM) increased linear velocity but lowered linearity. In contrast to caffeine, which stimulated sperm motility for less than 1 h, the effects of human serum lasted for more than 16 h.

Human Follicular Fluid Stimulates the Motility of Washed Human Sperm

Human follicular fluid (hFF) was collected by laparoscopic oocyte pickup during IVF to evaluate the effect of hFF on human sperm motility with a transmembrane migration method. Freshly ejaculated human sperm were washed with phosphate buffered saline (PBS) and mixed with either PBS or hFF. Amplitude of motility increases were 38% and 72% in washed fertile sperm and washed asthenozoospermic sperm when individual control motility was considered to be 100%. The stimulatory effect of hFF was lost when preheated at 100 degrees C for 30 minutes. hFF collected from mature follicles stimulated sperm motility better than that collected from intermediate or immature follicles. hFF did not stimulate the motility of unwashed sperm in freshly ejaculated human semen. A heat labile factor(s) in hFF may stimulate the motility of washed human sperm. Whether this factor could be used to improve the success rate of IVF and artificial insemination awaits further investigation.

Stimulation ofSpisulasperm motility by 5-hydroxytryptamine analogs

Summary Serotonin (5-hydroxytryptamine, 5-HT) added to cold-immobilized Spisula sperm reinitiated motility. The response was instantaneous and dose-dependent at concentrations ranging from 1 to 5 μm. The 5-HT agonists, 8-OH-DPAT, 5-methoxytryptamine and 2-methyl-5-HT, were effective inducers while RU 24969 and 5-hydroxyindole-3-acetic acid were not. Paralleling the stimulation of sperm motility, 5-HT increased oxygen consumption of Spisula sperm, reflecting acceleration of respiration. Of the various species tested, 5-HT stimulated only Spisula sperm.

Serum factors stimulate the motility of human spermatozoa

Motile human sperm were collected from a Percoll gradient and the effects on sperm motility of human serum, various serum fractions, follicular fluid and seminal plasma were assessed. In culture medium alone (RPMI-1640) sperm motility was lost after about 5 h. The addition of male blood serum both enhanced sperm motility and prolonged viability very significantly. Albumin, seminal plasma and follicular fluid all stimulated sperm motility but to a much lesser extent than did blood serum. No difference was noted between male serum or female serum which had been collected during the follicular or luteal phases of hormone-stimulated cycles and which contained high levels of oestradiol. Serum fractions obtained by separation on Sephacryl S-300 column were tested for their ability to enhance sperm motility. The most pronounced effect, much superior to that achieved by the albumin fraction, was obtained by a fraction with a molecular weight of around 200 kD. In conclusion, certain factors in human serum, which are different from albumin, strongly support sperm motility. The high serum concentrations of oestradiol resulting from hormone stimulation for in-vitro fertilization do not invalidate the use of serum from the same patient during sperm preparation, or in the medium used for ovum insemination and culture.

Relaxin in the Male1

Relaxin, a hormone usually associated with pregnancy, has been found in the semen plasma of many species. The prostate gland appears to be a source of relaxin. Relaxin stimulates sperm motility from suboptimal samples and increases sperm penetration into oocytes. Thus, relaxin may be an effective therapeutic agent in male infertility.

Effect of prostaglandins on human sperm function in vitro and seminal adenosine triphosphate content

The aim of the present study was to evaluate the effect of addition of physiologic amounts of different prostaglandins normally present in semen, on sperm motility, on sperm penetration capacity in cervical mucus in vitro, and on the adenosine triphosphate (ATP) concentration in semen. Semen samples were obtained from volunteers who were attending the fertility outpatient clinic. Sperm motility was measured on a video recorder with a built-in timer, sperm penetration by the Kremer test, and ATP by bioluminescence assay. The addition of 19-hydroxy prostaglandin (PG) E to ejaculates positively stimulated sperm motility and sperm penetration capacity. The opposite effect was observed with 19-hydroxy PGF. PGE1, PGE2, and PGF2 alpha had no effect on either parameter, while PGF1 alpha reduced the sperm motility. The addition of 19-hydroxy PGE to ejaculates increased and the addition of 19-hydroxy PGF reduced semen concentrations of ATP. However, only the last-mentioned effect was statistically significant (P less than 0.05). It is suggested that, in particular, 19-hydroxy PGE and 19-hydroxy PGF are important regulators of sperm motility and that the effect may be mediated via effects on the ATP content in the spermatozoa.

Effect of ace-inhibitors, calmodulin antagonists, acetylcholine receptor blocking, and alpha receptor blocking agents on motility of human sperm.

The purpose of this study was to investigate the influence of several pharmacological compounds on the motility and velocity of washed human spermatozoa. Results were evaluated by multiple exposure photography and computer-aided picture analysis. The motility-inhibiting effect of the antifertility drug gossypol was confirmed. Gossypol proved to be a potent inhibitor of the angiotensin converting enzyme (ACE) detectable in high concentrations in seminal plasma. However, human sperm motility was not inhibited during incubation with two other specific ACE-inhibitors (captopril, enalapril). On the contrary, high concentrations of captopril even showed a slight motility-stimulating effect. These results indicate no direct involvement of ACE in the regulation of sperm motility but suggest a direct interaction of gossypol with the plasma membrane of spermatozoa. To clarify whether or not gossypol blocks membranous ion transport, the effect of well-defined ion transport blocking agents on sperm motility was investigated. It was determined that the acetylcholine receptor blocker alpha-bungarotoxin and trifluoperazine, a specific calmodulin antagonist, inhibit sperm motility completely. Since stimulation of sperm motility by captopril may be due to an alpha-mimetic action of this compound, the influence of two alpha receptor blockers (bromocriptine, lisuride) on sperm motility was studied. Although lisuride inhibited sperm motility completely, bromocriptine revealed no influence. A temporary and reversible intervention with membrane transport processes could be a suitable way to regulate human sperm motility and male fertility.

Temperature-dependent effects of the components of kallikreinkinin system on sperm motility in vitro

The effect of kallikrein and bradykinin on sperm motility was studied. For investigation of whether the effect is not temperature dependent, sperm motility and velocity were measured after incubation with kallikrein or bradykinin at different temperatures. The effect of kallikrein on sperm motility and velocity was demonstrated significantly at 22 degrees C. At 37 degrees C, this effect was absent, but with captopril the effect of kallikrein on sperm velocity was observed. Bradykinin stimulated sperm motility and velocity at 22 degrees C and at 33 degrees C. However, it did not stimulate sperm motility at 37 degrees C. With 1.10 phenantroline, the effect of bradykinin on sperm motility was detected. These results indicate that kallikrein and bradykinin stimulate sperm motility and velocity and that their effects are strongly temperature dependent.

Sodium bicarbonate in seminal plasma stimulates the motility of mammalian spermatozoa through direct activation of adenylate cyclase.

Recently, a low molecular weight factor, which specifically stimulates sperm adenylate cyclase, was found in porcine seminal plasma (Okamura, N., and Sugita, Y. (1983) J. Biol. Chem. 258, 13056-13062). The purified factor was analyzed by 1H NMR, 13C NMR, infrared spectroscopy, and elementary analysis and identified as sodium bicarbonate. The effects of sodium bicarbonate both on adenylate cyclase activity in porcine spermatozoa and on sperm motility have been studied. Sperm adenylate cyclase was found to be specifically activated by bicarbonate over the physiological concentration range. In contrast, the adenylate cyclase activity in other tissues was not affected. The same concentration range of bicarbonate which resulted in activation of adenylate cyclase also stimulated sperm motility. The motility and enzyme activity of spermatozoa in all species so far tested (human, bovine, rat, mouse, and dog) were found to be similarly sensitive to bicarbonate concentration. These results show that the bicarbonate-sensitive adenylate cyclase system regulates sperm motility and suggest that this system is common to all mammals.

Involvement of calcium in the caffeine stimulation of human sperm motility.

The shape of the concentration-response curve and the amplitude of maximal motility increase for the stimulatory effect of caffeine on human sperm motility were similar to those of EGTA, a calcium chelator, and lanthanum chloride, a calcium entry blocker. On the other hand, the maximal motility stimulation induced by dibutyryl cyclic AMP was similar to that induced by trifluoperazine, a calmodulin antagonist. The antagonism of A23187 on the motility-stimulating effect of EGTA and caffeine was competitive in nature, while that on cyclic AMP was non-competitive. We proposed that there could be two mechanisms for caffeine to stimulate sperm motility: at higher concentrations, caffeine modified calcium translocation; at lower concentrations, caffeine increased cyclic AMP level. The importance of calcium in the regulation of human sperm motility was reconfirmed in this study.

The stimulatory effects of caffeine, theophylline, lysine-theophylline and 3-isobutyl-1-methylxanthine on human sperm motility.

The potencies of caffeine, theophylline, lysine-theophylline and 3-isobutyl-1-methylxanthine (IBMX) in stimulating sperm motility have been compared, and we have found IBMX to be significantly more potent than the other three compounds, which did not exhibit significant differences in potency from each other.

Stimulation of sperm motility and oxygen consumption of fowl spermatozoa by a low molecular weight fraction of seminal plasma.

Washed fowl spermatozoa were incubated in a phosphate buffer containing various concentrations of fowl seminal plasma at 41 degrees C, normal body temperature, and the motility and oxygen consumption of spermatozoa were determined. Immediately after the incubation, spermatozoa showed good motility in the various diluents. However, with concentrations of seminal plasma at or below 20%, spermatozoa quickly became immotile. In contrast, at concentrations higher than 40% seminal plasma, spermatozoa were motile even after 15 min. As the concentration of seminal plasma was increased, oxygen consumption of spermatozoa also increased. A filtrate of the seminal plasma, obtained by passing the fluid through an Amicon YM-2 ultra-filtration membrane (Mr less than 1000), also stimulated the motility and oxygen consumption of spermatozoa. These results suggest that some low molecular weight factor(s) in fowl seminal plasma stimulated motility and oxygen consumption of fowl spermatozoa at 41 degrees C. A physiological role of this factor(s) may be to assist passage of spermatozoa through the vagina after natural mating.

Stimulation of sperm respiration rates by speract and resact at alkaline extracellular pH.

At an extracellular pH of 6.6, a peptide (resact) isolated from the egg jelly of Arbacia punctulata increased the respiration rates of A. punctulata spermatozoa but did not activate sperm cells from Lytechinus pictus. In contrast, speract (Gly-Phe-Asp-Leu-Asn-Gly-Gly-Gly-Val-Gly), elevated the respiration rates of L. pictus but not A. punctulata spermatozoa. At normal seawater pH (7.6-8.0) egg jelly from A. punctulata, or egg jelly from L. pictus purified free of speract, inhibited L. pictus sperm respiration rates. Similarly, the egg jelly from L. pictus inhibited the respiration rates of A. punctulata spermatozoa. The jelly component responsible for the inhibition of respiration was nondialyzable. The inhibition of respiration induced by jelly could be reversed by the addition of speract to L. pictus spermatozoa and by the addition of resact to A. punctulata spermatozoa. Speract stimulated L. pictus sperm respiration half-maximally at about 1 nM in the presence of either heterologous or homologous (speract-free) jelly. Monensin A, an ionophore which elevates sperm intracellular pH, reversed the jelly inhibition of respiration. These results demonstrate that two peptides associated with eggs (speract and resact) can stimulate sperm motility and metabolism in the face of inhibitory components present in the egg jelly. Additionally, the peptides demonstrate species specificity.