Correlation Between the Sperm Motility and the Adenylate Cyclase Activity in Infertile Men/Über die Beziehungen zwischen der Motilität der Spermatozoon und der Adenylcyclase-Aktivität bei unfruchtbaren Männern

The relationship between the sperm motility and the adenylate cyclase activity in spermatozoa from patients with male infertility was investigated. Cyclic AMP contents were measured from 34 semen specimens and adenylate cyclase activity were assayed from 50 specimens. All semen specimens were collected from infertile men at our clinic by masturbation after 5 days sexual abstinence. Spermatozoa were washed and concentrated according to the method described by Harrison. The cAMP contents and the adenylate cyclase activity of spermatozoa were determined by radioimmunoassay. Positive correlations were found among the cAMP contents, the adenylate cyclase activity in human spermatozoa and the sperm motility. This result suggests that the sperm motility is regulated by the adenylate cyclase activity via cAMP and that poor sperm motility observed in infertile men is partially caused by the impairment of adenylate cyclase system.     

Über Beziehungen zwischen der Spermienmotilität und dem Gehalt an ungesättigten Fettsäuren sowie dem osmotischen Verhalten der menschlichen Spermienzelle

The relations between sperm motility and the content of lipids and fatty acids in sperm cells were investigated. In addition the osmotic volume changes of sperm cells were studied, by determination of progressive sperm motility, measurement of relative concentration of lipid-peroxy radicals in seminal plasma using chemoluminescence technique, gas-chromatographic determination of fatty acid pattern in sperm cells and in seminal plasma and by electronic measurement of the sperm cell volume. The impulse installment of chemoluminescence increased during the time of storage of the ejaculate. In contrast, this phenomenon was not observed in pure seminal plasma prepared by centrifugation immediately after liquefaction. The pattern of phospholipids and free fatty acids changed during storage of the ejaculate both in sperm cells and in seminal plasma. Sperm cells showed a significant increase of volume under hypotonic stress. The increase of volume is more distinct in spermatozoa with high progressive motility as in spermatozoa with low progressive motility. The determination of initial and late progressive motility enables the differentiation of two groups of sperm populations: one group with a medium initial motility and a normal decrease of motility during the following time and another group with excellent initial motility and an extreme decrease of motility following. The second group is characterized by an especially distinct increase of volume under hypotonic conditions.     

Neutralization of cytokine activity at the receptor level improves sperm motility in men with spinal cord injuries

Men with spinal cord injury (SCI) have a unique semen profile characterized by normal sperm concentrations but abnormally low sperm motility. Previous studies showed that elevated concentrations of cytokines in the seminal plasma of these men contribute to this condition. For example, when elevated concentrations of interlekin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) were immunoneutralized in the semen of men with SCI, sperm motility improved. The present study investigated if these cytokines act on sperm cell receptors to inhibit sperm motility. Semen was collected from men with SCI and from healthy non-SCI men. Sperm were separated from the seminal plasma by centrifugation. Eight identical aliquots of 5,000 sperm suspended in 50 microL of seminal plasma were prepared for each subject. Agents were added to the aliquots in order to neutralize IL-1beta, IL-6, and TNF-alpha at the receptor level. In SCI subjects, sperm motility improved in each treatment group compared with the untreated group, but statistical significance was reached only when neutralizing agents to all 3 cytokines were added. Improvement was less pronounced in subjects with close to normal semen cytokine concentrations or close to normal pretreatment sperm motility. In control subjects, IL-1beta, IL-6, and TNF-alpha were within normal values, and addition of receptor blockers to semen had no effect on sperm motility. These data support the hypothesis that cytokines act at the level of the sperm receptor to inhibit sperm motility. These data further support the notion that inactivating semen cytokines leads to improved sperm motility in SCI men. Our goal is to develop this finding into a treatment for low sperm motility in men with SCI.     

Bradykininase and protease inhibitors in seminal plasma of fertile and infertile men.

The level of protease acrosin in the seminal plasma of oligozoospermic men was significantly higher than that of normozoospermic men. The amount of bradykininase in the seminal plasma was very high in both normozoospermic and oligozoospermic patients. When the acrosin and kininase content was referred to one million spermatozoa, seminal plasma kininase was significantly enhanced in oligozoospermic men, while the acrosin activity was similar in normozoospermic fertile men and infertile men. Human seminal plasma inhibitor I (HUSI I) increased along with sperm count. Human seminal plasma inhibitor II (HUSI II) showed no change. The motility of spermatozoa was depressed in oligozoospermic patients.     

Pathophysiology of Clinical Varicoceles in Infertile Men

In infertile men, clinical varicoceles most often occur bilaterally. In our experience with these patients, both testicles are smaller than normal. We find more than 25% to 35% immature and tapered sperm in in the ejaculum of these men, and the motility of the sperm is usually low. We have found serotonin in the plasma of the varicoceles, and believe this biogenic amine is responsible for the poor sperm motility. We now agree that a subset of neuroendocrine cells in the prostate secrete serotonin. Bilateral varicocele surgery can improve the patient's fertility potential, and we advocate surgical treatment.     

Relationship of Sperm Acrosin Activity to Semen and Clinical Parameters in Infertile Patients/Die Beziehung der Akrosinaktivität zu verschiedenen Sperma- und klinischen Parametern bei infertilen Patienten

Acrosin activity (aa) was routinely measured in 189 infertile men who attended the hospital between March 1984 and January 1985. The evaluation of the male included semen analysis, microbial screening, postcoital testing (PCT), in vitro sperm penetration test (SPMT), and screening for anti-sperm antibodies in serum. The strongest positive correlations of aa were found for sperm motility, count, morphology, vitality and volume. In presence of a poor PCT result, aa was significantly reduced, even in patients with good motility in native semen. A similar result was obtained with the SPMT: reduced sperm density and poor sperm motility in the capillary after 2 hours were significantly correlated to reduced aa. Smokers exhibited lower aa in presence of normal sperm count and motility. In the infertile group aa was significantly lower than in the group of men whose spouses conceived. On the basis of our results, the routine determination of aa is not necessary, but it provides additional prognostic information in couples with unexplained infertility.     

The effect of spermine, spermidine and kallikrein on the triple adenosine triphosphatase enzyme activity of spermatozoa in males with oligoasthenozoospermia

Unknown factors in the seminal plasma of normal semen that affect the motility of spermatozoa have a positive effect on adenosine triphosphatase (ATPase) enzyme activity. In an attempt to produce such an effect, spermine, spermidine and kallikrein were added to the incubation media in which spermatozoal ATPase enzyme activity was determined. These seminal substances increased the triple ATPase enzyme activity of spermatozoa from oligoasthenozoospermic men. We propose that the ATPase enzyme activity of spermatozoa may indicate sperm motility as a biochemical test.     

Seminal arginase activity in infertility

Arginase (Arg) activity in seminal plasma and sperm cells from infertile men and healthy fertile donors was measured. There were no statistically meaningful differences in seminal plasma Arg activity between the two groups whereas sperm cells from oligospermic infertile men had a higher Arg activity compared with the controls. Some important correlations were established between sperm count and Arg activity (negative values) and sperm motility and Arg activity (positive values) in both sperm cells and plasma samples from infertile men. Results suggest that the arginine-nitric oxide pathway within sperm cells from oligospermic infertile men is disturbed by enhanced Arg activity. We think that this may play a part in sperm dysfunction and male infertility. Received: 22 October 1998 / Accepted: 1 October 1999     

弱精子症、少弱精子症患者血清、精浆和精子锌含量分析

目的:检测弱精子症和少弱精子症患者血清、精浆和精子锌的含量,分析锌含量的变化与精子密度和精子运动之间的关系。方法:按照WHO《人类精液及精子-宫颈粘液相互作用实验室检验手册》第四版的标准进行精液质量分析,随机筛选出90例弱精子症、60例少弱精子症患者以及20例精液质量正常的生育者作为研究对象,利用原子吸收光谱法检测其血清、精浆、精子的锌含量并进行统计学分析。结果:3组间血清锌含量没有显著差异;弱精子症、少弱精子症患者精浆锌含量均显著低于正常生育者(P<0.05);少弱精子症患者精子锌含量显著高于弱精子症患者和正常生育者(P<0.01)。结论:弱精子症、少弱精子症患者精子的发生及运动功能下降可能与精浆锌含量的低下呈正相关;但过高的精子锌含量与精子的发生和运动功能的关系尚不十分明了,有待进一步研究。     

Zur Bedeutung der linearen Cervixmucuspenetration (CMP) für die Bewertung der Spermatozoenqualität

Linear mucus penetration of spermatozoa from 75 arbitrary selected men was evaluated using a non-commercial bovine cervix mucus preparation in the same way as Penetrak, but using round glass capillary tubes instead of flat plastic tubes. The mean penetration value was 28.7 +/- 7.10 mm in 90 min and the mean sperm density 36.0 +/- 22.79 x 10(6) ml. Mucus penetration was more correlated to sperm density (r = 0.6) than to any other semen parameter. Consequently it seems to be necessary to evaluate a sliding discrimination index for adequate penetration rate depending on sperm density (regression line and confidence interval). Numerical methods for comparison of penetration rates are suggested.     

Impaired metabolism of guanidinoacetic acid in uremia

In order to investigate the guanidinoacetic acid (GAA) metabolism in uremia, we have measured serum guanidino compounds in patients with chronic renal failure (CRF) in comparison with normal subjects, and the renal content of GAA and glycine amidinotransferase (GAT) activity in the kidney of experimental CRF rabbits. Serum concentrations of guanidinosuccinic acid (GSA) and methylguanidine (MG) in the patients with CRF were higher than those in the normal subjects, as well as serum urea nitrogen (BUN) and creatinine (Cr) levels. The serum GAA levels were however, significantly lower and showed a tendency to decrease inversely with the elevation of BUN in the patients with CRF under conservative therapy. On the contrary, in the patients under maintenance hemodialysis (MHD) therapy, the serum GAA level did not decrease in spite of the elevation of BUN. Four anephric patients under MHD therapy showed a level of serum GAA similar to the other MHD patients. In the CRF rabbits, the renal GAA content was significantly lower than in the sham-operated rabbits and showed an inverse correlation with BUN. Renal GAT activity was also significantly lower in the CRF rabbits, showing a positive correlation with serum GAA concentration and an inverse correlation with BUN. These results indicate that renal GAT activity decreases as the BUN level rises in the course of renal damage, resulting in lower concentration of serum GAA in the uremic state; in a more advanced stage of renal failure, the inability of the kidney to synthesize GAA may be compensated by other organ(s). Some dialyzable substances which might inhibit renal GAT activity may also be present.     

Messung der Spermatozoenmotilität mittels Laser-Doppler-Spektroskopie im andrologischen Routinelabor

Sperm motility of 177 ejaculates from the andrology laboratory, University Clinic for Gynecology and Obstetrics, Graz/Austria, was evaluated in a comparative study. Motility was measured by Laser-Doppler-Spectroscopy (Lazymot) and by means of conventional microscopic estimations. For the first time results gained with Lazymot have been associated to different spermiogram diagnoses. In addition to measurements of percentages of total sperm motility, evaluations of mean sperm motility in micron/sec. have been performed. Correlation of results was good for both methods, besides the problem groups of ejaculates with sperm densities below ten millions of spermatozoa per milliliter. Motility characteristics of spermatozoa in an in vitro-Fertilization-Program have been subject to objective measurements with Lazymot for the first time. An enhancement of total motility (16%) and of mean spermatozoal velocity (36%) could be observed in the fertilization media after capacitation. Laser-Doppler-Spectroscopy represents a reliable and fast method for motility determinations in human ejaculate. It is suited for research purposes as well as for andrologic routine work. The operation of the Lazymot is considered to be unproblematic.     

Biosynthesis of guanidinoacetic acid in isolated rat tubules

Guanidinoacetic acid (GAA), a precursor of creatine, is an essential substrate for muscle energy metabolism. GAA is formed from arginine and glycine by glycine-amidinotransferase (GAT) mainly in the kidney. But mechanism of GAA synthesis in the kidney has not been defined. The author isolated renal tubules from rats and incubated them with various substrates. GAA was separated by HPLC and measured fluorometrically after reacting with 9, 10-phenanthrenequinone. The following results were obtained: 1. GAA synthesis in the isolated renal tubules was recognized without addition of any substrate. 2. A remarkable increase of the amount of GAA was observed in the presence of glycine and several amidine donors, such as arginine and canavanine. 3. The amount of GAA tended to increase until 3 hours. 4. D.L-norvaline and ornithine suppressed GAA synthesis in renal tubules. 5. Methionine suppressed GAA synthesis. 6. Creatine suppressed GAA synthesis. Negative feedback control of GAA synthesis by creatine was recognized in vitro. 7. GAA synthetic activity was not recognized after the addition of hydroxyurea, citrulline and argininosuccinic acid in the medium. 8. Low concentrations of methylguanidine and guanidinosuccinic acid decreased the amount of GAA. Concentrations used in the experiment were similar to those in uremic serum.     

Characterization of ultrastructural and metabolic abnormalities in semen from men with spinal cord injury

BACKGROUND: In men with spinal cord injury (SCI), fertility is impaired because of a combination of ejaculatory dysfunction and poor semen quality. We hypothesized that ultrastructural and metabolic abnormalities of sperm could be an underlying factor in infertility in these men. METHODS: To investigate mechanisms contributing to the abnormal sperm parameters, we analyzed seminal constituents and sperm ultrastructure in ejaculates from 7 men with SCI and compared them with 5 control subjects. Sperm adenosine triphosphate (ATP) content was measured using a firefly luciferase bioluminescent assay kit, and ultrastructure was evaluated by electron microscopy. Seminal oxidative stress (8-iso-prostaglandin F-2alpha [8-iso-PGF2alpha]) and transforming growth factor-beta1 (TGF-beta1) levels were measured by specific enzyme-linked immunoabsorbent assay kits. RESULTS: Semen samples from men with SCI showed azoospermia (3) and severe asthenospermia (2; motility 0-5%). A majority (65%) of sperm from asthenospermic samples showed degenerative changes and significant axonemal defects. Incubation of normal sperm with SCI seminal plasma induced a concentration-dependent decrease in sperm motility (43%) accompanied by a significant drop in intracellular ATP content (33%). Semen samples from men with SCI exhibited levels of 8-iso-PGF2alpha 3.5-fold higher than those from controls and levels of TGF-beta1 that were 10% higher than those from controls. CONCLUSION: Our results suggest that seminal constituents of men with SCI are detrimental to sperm movement and that ultrastructural degenerative changes may contribute to the impaired sperm motility and viability seen in these patients. These preliminary results must be confirmed in larger patient populations and longitudinal studies.     

Seminal transferrin levels in seminal plasma of fertile and infertile men.

Seminal plasma transferrin levels as well as serum FSH and LH levels were measured in fertile (normozoospermic) and infertile (oligozoospermic and azoospermic) men in an effort to find out whether transferrin levels correlated with sperm density and serum FSH and LH levels. Seminal plasma transferrin levels were found to be significantly lower (p < 0.0005) in the infertile group than the fertile group. Seminal plasma transferrin levels can be regarded as a functional parameter of Sertoli cell function in men.     

Melatonin and Sperm Motility/Melatonin und Spermatozoenmotilität

Several substances can interfere with microtubular function eg. colchicine. Melatonin, a hormone secreted by the pineal gland has similar effects as colchicine on microtubules. In this study melatonin levels were determined in both plasma and seminal plasma of patients with good or impaired motility and forward progression. There was no statistically significant difference between the mean plasma and seminal plasma values of patients with good or impaired motility and forward progression. There was no correlation between seminal plasma melatonin and impaired motility or any other semen parameter. There was also no correlation between plasma and seminal plasma concentrations of melatonin. High seminal plasma melatonin concentrations were not necessarily associated with impaired sperm motility. From these it is concluded that seminal plasma melatonin plays no important role in sperm motility.     

Effects of phosphodiesterase-5 inhibitors on sperm parameters and fertilizing capacity

The aim of this review study is to elucidate the effects that phosphodiesterase 5 （PDE5） inhibitors exert on spermatozoa motility, capacitation process and on their ability to fertilize the oocyte. Second messenger systems such as the cAMP/adenylate cyclase （AC） system and the cGMP/guanylate cyclase （GC） system appear to regulate sperm functions. Increased levels of intracytosolic cAMP result in an enhancement of sperm motility and viability. The stimulation of GC by low doses of nitric oxide （NO） leads to an improvement or maintenance of sperm motility, whereas higher concentrations have an adverse effect on sperm parameters. Several in vivo and in vitro studies have been carried out in order to examine whether PDE5 inhibitors affect positively or negatively sperm parameters and sperm fertilizing capacity. The results of these studies are controversial. Some of these studies demonstrate no significant effects of PDE5 inhibitors on the motility, viability, and morphology of spermatozoa collected from men that have been treated with PDE5 inhibitors. On the other hand, several studies demonstrate a positive effect of PDE5 inhibitors on sperm motility both in vivo and in vitro. In vitro studies of sildenafil citrate demonstrate a stimulatory effect on sperm motility with an increase in intracellular cAMP suggesting an inhibitory action of sildenafil citrate on a PDE isoform other than the PDE5. On the other hand, tadalafil＇s actions appear to be associated with the inhibitory effect of this compound on PDE11. In vivo studies in men treated with vardenafil in a daily basis demonstrated a significantly larger total number of spermatozoa per ejaculate, quantitative sperm motility, and qualitative sperm motility; it has been suggested that vardenafil administration enhances the secretory function of the prostate and subsequently increases the qualitative and quantitative motility of spermatozoa. The effect that PDE5 inhibitors exert on sperm parameters may lead to the improvement of the outcome of assi     

Effect of omega-3 polyunsaturated fatty acid supplementation on semen profile and enzymatic anti-oxidant capacity of seminal plasma in infertile men with idiopathic oligoasthenoteratospermia: a double-blind, placebo-controlled, randomised study

Effective medical treatments of infertile men with idiopathic oligoasthenoteratospermia (OAT) have yet to be determined. This study considered two major aims: (i) to measure the changes in semen parameters, omega‐3 fatty acids (FA) compositions and anti‐oxidant activity; (ii) to determine if the administration of omega‐3 FA affect semen quality in infertile men with OAT. Two hundred thirty‐eight infertile men with idiopathic OAT were randomised to eicosapentaenoic (EPA) and docosahexaenoic acids (DHA), 1.84 g per day (EPAX 5500TG; Lysaker, Norway), or placebo for 32 weeks. The semen parameters were assessed according to WHO criteria, and the EPA and DHA concentrations were determined in red blood cells (RBCs), seminal plasma and sperm cells at baseline and 32‐week treatment period. Of randomised subjects, 211 (88.7%) completed the full 32‐week randomisation period. The anti‐oxidant status of seminal plasma was also evaluated by measuring the superoxide dismutase (SOD) and catalase‐like activity. In the total group of participants, all EPA and DHA levels in RBC, and seminal plasma, were statistically significantly correlated with those in spermatozoa (both P = 0.001). A significant improvement of sperm cell total count (from 38.7 ± 8.7 ′ 10⁶ to 61.7 ± 11.2 ′ 10⁶, P = 0.001) and sperm cell concentration (from 15.6 ± 4.1 ′ 10⁶ per ml to 28.7 ± 4.4 ′ 10⁶ per ml, P = 0.001) was observed in the omega‐3 group. A significant positive correlation was found between the EPA and DHA in seminal plasma and the semen parameters. Seminal plasma EPA and DHA concentrations were positively correlated with seminal plasma SOD‐like and catalase‐like activity (both P = 0.001). In seminal plasma, both SOD‐like and catalase‐like activity were positively correlated with sperm count, sperm motility, and sperm morphology. Oligoasthenoteratospermic men with low levels of EPA and DHA may benefit from omega‐3 FA supplementation. Further studies are warranted to shed more light on this important issue.     

Inhibition of sialyl transferase activity by gossypol acetic acid in human seminal plasma

Seventeen aliquots of 15 microliters seminal plasma of human origin were incubated with 25 micrograms, 15 micrograms, 5 micrograms and 2.5 micrograms gossypol acetic acid (GAA), dissolved in BWW containing 0.9% sodium chloride and 0.9% benzyl alcohol, at 37 degrees C for 60 minutes. Following incubation, activity of sialyl transferase (S.T.) was determined by a procedure involving incorporation of radioactive sialic acid into asialofetuin. The activity of S.T., expressed as cpm per hour per 15 microliters seminal plasma was compared to controls consisting in incubation of sperm in BWW containing 0.9% benzyl alcohol and 0.9% sodium chloride. The activity of S.T. in controls represented 61.3 +/- 8.0%-67.7 +/- 8.9% of the activity obtained by incubation with BWW only. GAA was found to exert a dose-dependent inhibition of S.T. activity, ranging from 38.3 +/- 20.6% to 53.4 +/- 19.4% (with 25 micrograms) and from 11.3 +/- 14.8% to 21.9 +/- 14.8% (with 2.5 micrograms).