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PubMed2005

Deficiency of SPAG16L causes male infertility associated with impaired sperm motility.

The axonemes of cilia and flagella contain a "9+2" structure of microtubules and associated proteins. Proteins associated with the central doublet pair have been identified in Chlamydomonas that result in motility defects when mutated. The murine orthologue of the Chlamydomonas PF20 gene, sperm-associated antigen 16 (Spag16), encodes two proteins of M(r) approximately 71 x 10(3) (SPAG16L) and M(r) approximately 35 x 10(3) (SPAG16S). In sperm, SPAG16L is found in the central apparatus of the axoneme. To determine the function of SPAG16L, gene targeting was used to generate mice lacking this protein but still expressing SPAG16S. Mutant animals were viable and showed no evidence of hydrocephalus, lateralization defects, sinusitis, bronchial infection, or cystic kidneys-symptoms typically associated with ciliary defects. However, males were infertile with a lower than normal sperm count. The sperm had marked motility defects, even though ultrastructural abnormalities of the axoneme were not evident. In addition, the testes of some nullizygous animals showed a spermatogenetic defect, which consisted of degenerated germ cells in the seminiferous tubules. We conclude that SPAG16L is essential for sperm flagellar function. The sperm defect is consistent with the motility phenotype of the Pf20 mutants of Chlamydomonas, but morphologically different in that the mutant algal axoneme lacks the central apparatus.

Animals↗
PubMedDate not supplied

Effect of acute androgen withdrawal by GnRH antagonist on epididymal sperm motility and morphology in the cynomolgus monkey.

Hormonal male contraception requires an induction phase before azoospermia and contraceptive safety are achieved. The nature of spermatozoa that may be ejaculated during this induction phase was studied in a nonhuman primate. The GnRH antagonist Cetrorelix was administered daily to five cynomolgus monkeys to induce testicular regression, and the vehicle was given to five control animals. Within 16 days, the antagonist reduced androgens by 80% in the serum and by 50% in the epididymis. Sperm were obtained by mincing different epididymal regions and were examined for morphology (subjectively) and motility (objectively) after removal of the organs 16 and 25 days after continuous treatment. Spermatozoa entering the epididymis of monkeys undergoing regression differed from those of vehicle-treated controls in their greater susceptibility to disruption during preparation for morphological staining. The acquisition of motility by sperm in the epididymides attached to regressing testes occurred in the same epididymal region as controls but did not achieve the median velocities attained by sperm in controls during epididymal passage. Values for most sperm motion parameters developed as in the controls, and, during epididymal passage, sperm developed resistance to stresses encountered during preparation for morphological analysis. These observations suggest that spermatozoa ejaculated before spermatogenesis ceases may be potentially fertilizing because epididymal maturation continues in an androgen-deprived organ. From these preclinical studies, it can be concluded that in men, applying hormonal contraception precautions against pregnancy must be recommended before azoospermia is induced, since the epididymis can partially compensate for poor-quality sperm produced by a regressing testis even when levels of circulating androgens and tissue androgens are low.

Androgen Antagonists↗
PubMed2000

Effect of hepatocyte growth factor on sperm motility.

PROBLEM: Hepatocyte growth factor (HGF) exists abundantly in seminal plasma and its receptor, c-met, is expressed on spermatozoa. Considering its motogenic activity, we speculated that HGF might affect the movement ability of spermatozoa. METHODS: Recombinant HGF was added to washed spermatozoa and their movements were analyzed using a computer-assisted sperm analyzer. The concentration of HGF in the seminal plasma of infertile patients (n = 83) was measured by ELISA, and the data were compared with their hormonal profile and semen parameters. RESULTS: The HGF physiological concentration (1 ng/mL) maintained the motility of sperm after a long incubation, though the difference was not statistically significant. Recombinant HGF did not affect the linearity or frequency of movement, which suggested that it does not evoke the hyperactivation of spermatozoa. The concentration of HGF in seminal plasma did not correlate with any clinical parameter of the patients. CONCLUSIONS: These findings contradict the theory that HGF controls the movement of sperm. The main role of this axis in the male reproductive system might be maturation in the epididymis.

Hepatocyte Growth Factor↗
PubMedDate not supplied

Provocation testing of human sperm motility using energy substrates and activators of the cyclic nucleotide system. I. Establishment of conditions for response testing.

In order to establish a series of provocation tests to evaluate the integrity of the sperm cAMP pathway, manganese (Mn), 2-deoxyadenosine (DEA) (via adenylyl cyclase), and methyl-isobutyl-xanthine (MIX) (via phosphodiesterase) were tested for their capacity to activate the progressive motility of human sperm. Optimal responses were obtained using washed sperm previously incubated for 3 hours in substrate-poor medium (Hepes-buffered saline). Longer periods of incubation required the presence in addition of an energy substrate such as glucose. Exposure of sperm to seminal plasma for 24 hours prior to washing attenuated the responsiveness of the sperm to the different activators. Preliminary studies on the activation of the progressive motility of washed sperm from four normozoospermic men under fertility investigation, prepared under identical conditions, revealed differences in the pattern of response which may have pathophysiological relevance.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Cyclic AMP-dependent protein kinases in semen from men with subnormal sperm motility or morphology.

Photoaffinity labelling by 8-N3-/32P/cAMP of human sperm homogenates with normal pathology and normal progressive motility of the gametes (N) revealed the presence of 2 specific cAMP-binding activities with MW 47 000 (R-I) and 52 000 (R-II). Similar amounts of R-I and R-II were found in sperm homogenates obtained from semen samples with either reduced progressive motility (A50: 30-50% progressive motility and A30: less than 30% progressive motility) or abnormal morphology of the gametes (T: 5-30% normal heads). In contrast, the seminal plasma of the respective semen samples of N, A50, A30 and T incorporated the 8-azido cAMP photolabel in similar quantities into 2 additional cAMP-binding proteins with MW 42 000 and 37 000. Quantitative analysis of the photoaffinity labelling of the seminal plasma obtained from normal (N) or subnormal semen (A50, A30, T) showed that cAMP was predominantly bound to the 37 000 protein. Furthermore, the cAMP-dependent protein kinase and cAMP-binding activities of sperm homogenates were quantitatively comparable within the 4 groups. These results provide the first evidence that neither quantitative nor qualitative differences in the molecular and/or enzymatic properties of cAMP-dependent protein kinases can be detected between normal human sperm (N) and those with either reduced progressive motility (A50, A30) or abnormal morphology (T).

Adolescent↗
PubMed1978

The effect of temperature on sperm motility. II. Is bacterial growth a factor?

The previous demonstration that sperm kept at body temperature (37 degrees C) had a marked deterioration in motility accompanied by an overgrowth of bacteria in the semen and a concomitant decrease in pH led to this study to test the hypothesis that the decrease in motility was caused by the bacteria or by bacterial alteration of seminal pH. Semen specimens from fertile prevasectomy patients with and without added antibiotics were maintained at 20 degrees C and 37 degrees C and evaluated at 3, 12, and 18 hours after collection. There was still a significant deterioration in spermatozoal motility in the samples kept at 37 degrees C even when bacterial growth and change in pH were prevented by buffered antibiotics. Although the decrease in spermatozoal motility at body temperature may in part be attributed to bacterial growth or the products of bacterial metabolism, clearly another factor is present related to time and temperature and independent of the presence of bacteria.

Humans↗
PubMed2006

Effects of electromagnetic radiation from a cellular phone on human sperm motility: an in vitro study.

BACKGROUND: There has been growing public concern on the effects of electromagnetic radiation (EMR) emitted by cellular phones on human health. Many studies have recently been published on this topic. However, possible consequences of the cellular phone usage on human sperm parameters have not been investigated adequately. METHODS: A total number of 27 males were enrolled in the study. The semen sample obtained from each participant was divided equally into two parts. One of the specimens was exposed to EMR emitted by an activated 900 MHz cellular phone, whereas the other was not. The concentration and motility of the specimens were compared to analyze the effects of EMR. Assessment of sperm movement in all specimens was performed using four criteria: (A) rapid progressive, (B) slow progressive, (C) nonprogressive, (D) no motility. RESULTS: Statistically significant changes were observed in the rapid progressive, slow progressive and no-motility categories of sperm movement. EMR exposure caused a subtle decrease in the rapid progressive and slow progressive sperm movement. It also caused an increase in the no-motility category of sperm movement. There was no statistically significant difference in the sperm concentration between two groups. CONCLUSIONS: These data suggest that EMR emitted by cellular phone influences human sperm motility. In addition to these acute adverse effects of EMR on sperm motility, long-term EMR exposure may lead to behavioral or structural changes of the male germ cell. These effects may be observed later in life, and they are to be investigated more seriously.

Cell Phone↗
PubMed1977

Turbidimetric analysis of human sperm motility.

A turbidimetric method has been developed for determining rapidly the fraction of sperm in human ejaculates which show the most vigorous motility. The method is based on the fact that sperm cells so endowed will be the first to swim upward into clear medium from a concentrated cell suspension at the bottom of an optical cuvette. This results in a time-dependent increase in turbidity in the medium which is recorded spectrophotometrically as an increase in absorbance. The determination requires 10 minutes and yields both the fraction of rapidly moving sperm, FRM, and their average velocity, VRM. Examination of 25 samples yielded FRM values of 10% or lower, whereas values for VRM averaged about 100 microns/second. These vigorously motile cells may be the best candidates for fertilization, and samples with a high fraction of such cells should have high fertilizing capacity. It is suggested that this simple turbidimetric test be used in evaluation of human semen as a possible indicator of fertilizing capacity.

Humans↗
PubMed1985

Cross-link formation at the head-tail junction of mammalian spermatozoa during aging is dependent on sperm motility.

A high percentage of the heads of mouse, hamster, and rabbit spermatozoa were detached from their tails by vortexing a suspension of spermatozoa that had been incubated with dithiothreitol (DTT), a sulfhydryl reagent. Similar treatment of spermatozoa that had been aged under physiologic conditions for several hours and were still motile before reaction with DDT gave a much lower percentage of head detachment. This stabilization of the sperm head-tail junction developed only if spermatozoa were motile during aging. n-Butylamine also induced head detachment of mouse spermatozoa. Motile and immotile mouse spermatozoa became resistant to n-butylamine when aged in physiologic medium and buffer, respectively. However, stabilization developed much faster if spermatozoa were motile. Stabilization of the head-tail junction of motile spermatozoa to the reagents occurred over the time periods required for capacitation and the development of hyperactivated motility. Development of resistance to the two reagents may be biochemical events associated with capacitation.

Aging↗