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A possible role of Fas antigen in ejaculated spermatozoa of fertile bulls: an immunocytochemical quantitative approach.

The Fas/Fas L system is a widely recognized apoptosis signal transduction pathway in which transmembrane receptor protein (Fas) triggers a programmed cell death when bound by the Fas ligand (Fas L). This system in the testis is believed to be a paracrine signaling system by which Sertoli cells expressing Fas L can initiate killing of Fas-expressing germ cells during spermatogenesis. So far, the presence of Fas antigen in ejaculated spermatozoa was related only to subfertility or infertility conditions. We demonstrated for the first time that normal ejaculated spermatozoa also express Fas antigen. Our data showed that a large percentage of normal ejaculated spermatozoa of fertile bulls are immunocytochemically positive for Fas. Our observations provide further evidence of the "regionalization" of sperm membrane antigens. Furthermore, we suggest that in mature fertile ejaculated spermatozoa the Fas antigen may also provide resistance to programmed cell death, like in some other cells expressing molecules that inhibit the signals induced by Fas or the death program itself. In addition, we suggest that Fas antigen can partly protect the spermatozoa against apoptosis induced by lipoperoxidative damage that can occur spontaneously in the male gamete at various stages in its lifetime.

Animals↗

Abdominal electric stimulation facilitates penile vibratory stimulation for ejaculation after spinal cord injury: a single-subject trial.

OBJECTIVE: To compare the success rate of penile vibratory stimulation (PVS) alone with PVS and abdominal electric stimulation (AES). DESIGN: Single-subject trials. SETTING: Outpatient. PARTICIPANT: Man with chronic T3 complete (American Spinal Injury Association Impairment Scale grade A) spinal cord injury. Spasticity, Babinski response, anal wink, and bulbocavernosus reflexes were all present. INTERVENTION: Stimulation was presented to the frenulum using a Ferti Care Personal vibrator set at maximal settings (frequency, 110 Hz; amplitude, 3.55 mm). AES was applied to the abdomen using a commercially available muscle stimulator at maximal stimulus intensity and duration settings. Trials were randomized to PVS only or PVS plus AES. MAIN OUTCOME MEASURES: Presence or absence of ejaculation, and time to ejaculation. RESULTS: Only 4 of 30 trials were positive with PVS alone, while 31 of 34 trials were positive with PVS plus AES. Additionally, 17 of 26 PVS trials, which were initially negative with PVS alone, were then positive with the addition of AES. This represents a clinically relevant improvement with use of AES. Time to ejaculation for positive trials with either technique was not statistically significant. CONCLUSIONS: AES significantly lowered the threshold for ejaculation elicited with vibratory stimulation and increased the success rate over that when PVS alone was used.

Adult↗

Novel presentation of retroperitoneal germ cell tumor with loss of ejaculation but preservation of erection in two patients.

OBJECTIVE: To examine the effect of large-volume retroperitoneal germ cell tumor on nerve fibers required for erection and ejaculation. DESIGN: Retrospective case reports. SETTING: Cancer treatment center. PATIENT(S): Two male patients presenting with loss of ejaculation but preservation of erection. RESULT(S): Retroperitoneal lymph nodes lie very close to the sympathetic nerve fibers that control ejaculation. Large-volume tumors would encase the sympathetic plexuses at L1 to L3, making ejaculation impossible. Parasympathetic fibers arise from S2 to S4, so they would not be damaged, preserving erection. CONCLUSION(S): Thorough history taking is important in the investigation of infertility. Presentation with these symptoms requires further investigation at an early stage to exclude retroperitoneal tumor.

Adult↗

Sperm competition promotes the exploitation of rival ejaculates.

In many polyandrous species, the second male to mate with a female has fertilization priority. Strategic mechanisms generating this pattern tend to involve facultative increases in ejaculate size by informed males. Here we suggest a novel mechanism to generate second male precedence in internal fertilizers, based on the established fact that the female site of insemination is hostile to sperm, and that non-sperm components of the ejaculate frequently act to ameliorate these hostile conditions. We suggest that in species where female remating is frequent and rapid, second male sperm precedence may be due to the prior buffering of the female tract by previous males' ejaculates. In this scenario, second male costs are lower due to reduced sperm mortality and/or the redundancy of seminal fluid. Contrary to many classical predictions, second males may gain a paternity advantage despite investing less in an ejaculate.

Animals↗

Ejaculation latency times and their relationship to penile sensitivity in men with normal sexual function.

PURPOSE: There is a need for objective and validated measurements of ejaculation latency time and penile sensitivity in men with normal sexual function. We determined 1) the normal range and repeatability of ELT in a laboratory vs at home masturbation and intercourse in normal men, 2) the threshold and repeatability of penile sensitivity on 6 penile surface areas measured by 2 vibrometers and 3) whether penile sensitivity correlates with ejaculation latency time. MATERIALS AND METHODS: A total of 58 healthy volunteers between 20 and 40 years old provided ejaculation latency times during 3 procedures and were evaluated with a biothesiometer and SMV-5 vibrometer (Suzuki-Matsuoka, Teknologue, Tokyo, Japan) on 6 penile surface areas. RESULTS: Ejaculation latency time was highest during intercourse (median 8.25 minutes, range 1.32 to 18.31), lower in the laboratory (median 7.22, range 1.37 to 18.79) and lowest during masturbation (median 4.89, range 1.08 to 14.19). The 3 ELT scores were highly reproducible within subjects (ICC 0.88 to 0.93). There was high variability among subjects. Vibrotactile thresholds on 6 penile surface areas were also similar and highly repeatable for the 2 vibrometers (ICC 0.81 to 0.96). However, there was no correlation between penile sensitivity and ELT (R2 less than 8%). CONCLUSIONS: ELT in the laboratory is lower than during intercourse and higher than during masturbation. Vibrometers produce reliable and repeatable penile vibrotactile threshold results. However, penile sensitivity measurements do not correlate with ELT in men with normal sexual function.

Adult↗

Effect of administration of prostaglandin F2alpha or presence of an estrous teaser bitch on characteristics of the canine ejaculate.

Semen was collected from eight dogs after SC administration of 0.1mg/kg PGF2alpha or 0.6 mL 0.9% NaCl solution 15 min prior to collection in the presence or absence of an estrous teaser bitch (switchback design; all dogs given all four treatments in random sequence). There were more spermatozoa (P=0.02) in ejaculates collected after administration of PGF2alpha in the presence of an estrous teaser bitch ((852+/-736)x10(6), mean+/-S.D.) than in ejaculates collected in saline-treated dogs in the absence of a teaser bitch ((371+/-620)x10(6)). However, the number of spermatozoa in the ejaculate of dogs given PGF2alpha in the absence of a teaser bitch and in dogs given saline in the presence of a teaser bitch ((556+/-494 and 600+/-622)x10(6), respectively) were not significantly different from each other or from the other two groups. The percentage of morphologically normal spermatozoa did not vary by treatment (P=0.51). In conclusion, treatment with PGF2alpha and presence of a teaser bitch had an additive effect on the number of spermatozoa. This, coupled with relatively minor side-effects, suggests this is a useful technique to increase number of spermatozoa in a single canine ejaculate.

Animals↗

Contractile activity of the prostate at ejaculation: an electrophysiologic study.

OBJECTIVES: To investigate the hypothesis that the prostate contracts at ejaculation to push its secretions into the urethra. Although it has been mentioned that the prostate contracts at ejaculation, a report of this finding could not be traced in published studies. METHODS: The electromyographic activity of 8 canine prostates was recorded by applying an electrode to the prostate. The prostatic urethral pressure was simultaneously measured by means of a manometric catheter. The prostatic electromyographic and urethral pressures were recorded at rest and on ejaculation by penile electrovibration. RESULTS: The prostatic slow waves (SWs) and action potentials (APs), as well as the urethral pressure at rest, showed a significant increase during the ejaculatory bouts (P < 0.05 and P < 0.05, respectively). The SWs, APs, and pressure increase occurred simultaneously with each bout of ejaculatory spurt, which occurred at mean intervals of 1.1 +/- 0.02 seconds and a number of 4.6 +/- 1.2 bouts. CONCLUSIONS: The electric waves discharged from the prostate at rest seemed to produce prostatic contractions, which cause prostatic urethral pressure increases. At ejaculation, the intermittent increase of the wave variables and urethral pressure coincided with the ejaculatory spurts, apparently denoting intermittent prostatic smooth muscle contractions. These contractions seem to squeeze the prostatic secretions into the prostatic urethra.

Animals↗

Facilitation of ejaculation after methamphetamine administration in paradoxical sleep deprived rats.

This study investigated the effects of methamphetamine (MA) on genital reflexes in paradoxical sleep deprived (PSD) rats. Different doses of MA (0, 4, 16 and 64 mg/kg) were acutely given after PSD or the equivalent time to control animals. We observed enhancement of spontaneous ejaculation in PSD rats with larger doses of MA, the highest of which induced ejaculation in 100% of the PSD rats. This was significantly higher than the 30% in the control. Although testosterone exerts motivational effects on male sexual behavior, our data shows that testosterone levels were lower after the PSD period in saline and in the 64 mg/kg MA groups, which present ejaculation at different rates (20% and 100%, respectively). Progesterone levels were significantly higher in PSD-saline in relation to control group and in the 16 and 64 mg/kg of MA groups compared to the other doses. Since PSD induces dopaminergic alterations and dopamine (DA) has a key role in male sexual behavior, plasma DA was also measured. The DA concentration was enhanced in all PSD groups compared with their control group. The mechanism that activates steroid hormones may represent an important physiological effect through which neurotransmitters can affect behavioral events. These data show that MA facilitates ejaculation in PSD rats, however, further studies need to be carried out in order to clarify the hormonal-neurochemical mechanisms involved.

Analysis of Variance↗

Conception following insemination with a freeze-preserved retrograde ejaculate.

Retrograde ejaculation, an infrequent cause of male infertility, may be the sequela of prostate or bladder neck surgery or the result of interruption in the sympathetic innervation to the bladder neck. The diagnosis is established by history and examination of the urine. In infertile couples artificial insemination homologous (AIH) using retrograde ejaculate recovered from the bladder has been successfully accomplished, but conception has occurred only in isolated cases. A literature review of the subject is presented. The technique of semen recovery from the bladder is time-consuming and uncomfortable to the patient, while the quality of the semen recovered is variable and the risk of iatrogenic urinary tract infection is increased. To avoid the above problems, and to have sperm available for AIH at the time of induced ovulation in an anovulatory wife, we were able to freeze-preserve ejaculate recovered from the bladder for future use. A case of conception following AIH with freeze-preserved retrograde ejaculate is presented.

Adult↗

Sperm parameters and ejaculation before and after operative treatment of patients with germ-cell testicular cancer.

In testicular tumor patients, the stage of disease is most accurately determined by retroperitoneal lymph node dissection (RLND) and histologic examination of the operative specimen. The resection of possibly metastatic nodes is essential for securing a good prognosis. However, the most frequently encountered loss of ejaculatory function is a major disadvantage of radical RLND. In patients who intraoperatively proved to be free of metastases, we successfully employed a modified technique aiming at the preservation of sympathetic nerve fibers which mediate ejaculation. In 29 of 37 patients (78%), postoperative ejaculation was antegrade. It was retrograde in 5 of 37 patients (13.5%); 3 patients had no emission. These results are retrospectively compared with results of radical RLND in 87 patients of whom 64% suffered a total loss of ejaculation and only 23% had antegrade ejaculation. RLND did not affect sperm count, motility, and cell morphology. Potentia coeundi was preserved in all cases, although 27% of patients experienced diminished erectility or libido.

Adolescent↗

The effects of oral administration of prostaglandin E2 on the human ejaculate.

A single 1 mg dose of prostaglandin (PG) E2 was given orally to 19 men. Ejaculates were obtained 90 minutes and 24 and 48 hours thereafter. Before treatment, each man delivered another three semen samples with the same time intervals as during the study period. PGE2 was also administered to seven men during naproxen treatment and ejaculates were sampled as above. PGE2 did not influence the 90 minutes' posttreatment ejaculates, but after 24 hours there was a significant (P less than 0.05) decrease in sperm counts as compared to the control samples. The change in sperm count was suggested to be due to an effect of PG on the contractile elements in the deferent duct. Sperm motility, viability, and morphology as well as semen volume and adenosine triphosphate (ATP) content remained unchanged. The total semen PGE content was increased 24 hours after treatment from 169 micrograms/ejaculate to 213 micrograms/ejaculate (P = 0.02). In the combined PGE2/naproxen treatment the PGE levels were significantly (P less than 0.05) elevated in the ejaculate 48 hours after treatment. The increase may indicate an increased de novo synthesis of prostaglandins. Based on the results from the analysis of the composition of the 19-hydroxy PGF-isomers with and without naproxen treatment, it is speculated that oral PGE2 influences the cyclo-oxygenase activity.

Administration, Oral↗

Semen quality in dogs and the influence of a short-interval second ejaculation.

Semen quality was examined in each of 65 known fertile dogs. Values were found to be similar to those previously published, although an apparent breed influence was demonstrated, with German shepherd dogs producing ejaculates of larger volume and greater total spermatozoal output than other breeds. A second ejaculate was collected from each dog with a mean interval of 63 min. The second samples had significantly lower values for the volume of the second fraction, the spermatozoal concentration and the total spermatozoal output. There were no differences for the percentage motility or the percentage of morphologically normal live spermatozoa. While there was no increase in semen quality of the second ejaculate, the technique may be useful since it results in the collection of approximately 70% more spermatozoa than a single ejaculate. These spermatozoa also had normal motility and morphology and could, therefore, be used for insemination or cryopreservation.

Animals↗

Efficacy and tolerability of dapoxetine in treatment of premature ejaculation: an integrated analysis of two double-blind, randomised controlled trials.

BACKGROUND: No drugs are approved for treatment of premature ejaculation. Our aim was to determine the efficacy and tolerability of on-demand dapoxetine in patients with severe premature ejaculation. METHODS: We determined the efficacy of dapoxetine in a prospectively predefined integrated analysis of two 12-week randomised, double-blind, placebo-controlled, phase III trials of identical design done independently, in parallel, at 121 sites in the USA. Men with moderate-to-severe premature ejaculation in stable, heterosexual relationships took placebo (n=870), 30 mg dapoxetine (874), or 60 mg dapoxetine (870) on-demand (as needed, 1-3 h before anticipated sexual activity). The primary endpoint was intravaginal ejaculatory latency time (IELT) measured by stopwatch. Safety and tolerability were assessed. All analyses were done on an intention-to-treat basis. The trials are registered at ClinicalTrials.gov, numbers NCT00211107 and NCT00211094. FINDINGS: 672, 676, and 610 patients completed in the placebo, 30 mg dapoxetine, and 60 mg dapoxetine groups, respectively. Dapoxetine significantly prolonged IELT (p<0.0001, all doses vs placebo). Mean IELT at baseline was 0.90 (SD 0.47) minute, 0.92 (0.50) minute, and 0.91 (0.48) minute, and at study endpoint (week 12 or final visit) was 1.75 (2.21) minutes for placebo, 2.78 (3.48) minutes for 30 mg dapoxetine, and 3.32 (3.68) minutes for 60 mg dapoxetine. Both dapoxetine doses were effective on the first dose. Common adverse events (30 mg and 60 mg dapoxetine, respectively) were nausea (8.7%, 20.1%), diarrhoea (3.9%, 6.8%), headache (5.9%, 6.8%), and dizziness (3.0%, 6.2%). INTERPRETATION: On-demand dapoxetine is an effective and generally well tolerated treatment for men with moderate-to-severe premature ejaculation.

Adult↗

Painful ejaculation and urinary hesitancy in association with antidepressant therapy: relief with tamsulosin.

Painful ejaculation has been reported in association with a variety of antidepressants such as the tricyclic antidepressants (TCAs, e.g. clomipramine, imipramine, desipramine, protriptyline, amoxapine), the selective serotonin reuptake inhibitors (SSRIs, e.g. fluoxetine), venlafaxine and the MAOIs. Apart from lowering the dose and changing the antidepressant, no strategies are available to treat this side effect. In this paper, painful ejaculation following the administration of reboxetine is described in two patients. Both patients were treated concomitantly with the selective alpha(1A)-adrenoceptor antagonist, tamsulosin. A re-challenge was performed in one patient. The Hamilton Depression Rating Scale (HAM-D), the American Urological Association symptom index, a (dis)satisfaction item score and the Udvalg for Kliniske Undersoegelser (UKU-side effect rating scale) were used to assess the treatment. Tamsulosin rapidly and completely resolved the painful ejaculation and urinary hesitancy in both patients. A re-challenge in one patient resulted in a prompt reappearance of both side effects. Tamsulosin resolved the problem of painful ejaculation in these patients; however, larger studies are needed to confirm these results.

Adrenergic alpha-Antagonists↗

Presence and significance of somatic cell apoptosis markers in human ejaculated spermatozoa.

Ejaculated spermatozoa, particularly in infertile men, have been shown to display morphological and biochemical features that are typical of an apoptotic phenotype in somatic cells. Deregulation of apoptosis is known to play roles in a number of disease processes, but roles for apoptosis in ejaculated spermatozoa and male infertility are poorly defined or have not been studied. Preliminary data demonstrated that populations of ejaculated spermatozoa express: (i) various degrees of plasma membrane translocation of phosphatidylserine and DNA fragmentation; and (ii) active caspase-3, the main executor of apoptosis in somatic cells, with an apparent exclusive cellular location to the mid-piece. Tests are currently being carried out on the effects of well-known apoptosis agonists and caspase inhibitors on such markers using purified populations of leukocyte-free ejaculated human spermatozoa. The main objective is to determine if somatic cell apoptosis markers are relevant indicators and/or causative factors of male infertility.

Apoptosis↗

Effect of ejaculate, bull, and a double swim-up sperm processing method on sperm sex ratio.

Offspring gender preselection has applications of considerable economic, health and ecological interest. In this study we analysed modifications of the percentages of spermatozoa bearing Y and X chromosomes when semen samples are submitted to a double swim-up technique as a possible method for producing embryos of known sex with in vitro fertilisation protocols. As an initial experiment to provide accurate evaluation of the method we determined the possible incidence of natural deviations in the primary sex ratio between bulls or ejaculates, analysing the percentage of Y-chromosome DNA bearing spermatozoa (%Y-CDBS) with a polymerase chain reaction (PCR) amplification of X- and Y-specific fragments. Ejaculates were tested by direct semiquantitative PCR sexing and by sexing blastocysts produced in vitro with these spermatozoa. Bulls and ejaculates did not have any effect on the %Y-CDBS or on the sex ratio of embryos produced in vitro using these ejaculates. However, our double swim-up sperm preparation method produced differences in %Y-CDBS in some of the sperm fractions, suggesting that there are intrinsic differences in capacitation of X- and Y-bearing spermatozoa that might be used to produce embryos of the desired sex with in vitro fertilisation.

Animals↗

Antioxidant supplementation of boar spermatozoa from different fractions of the ejaculate improves cryopreservation: changes in sperm membrane lipid architecture.

Previous studies have shown sperm quality after cryopreservation differs depending on the fraction of seminal plasma the boar spermatozoa are contained in. Thus, spermatozoa contained in the first 10 ml of the sperm-rich fraction (portion I) withstand handling procedures (extension, handling and freezing/thawing) better than those contained in the latter part of a fractionated ejaculate (second portion of the sperm-rich fraction and the post-spermatic fraction; portion II). The present study evaluated whether an exogenous antioxidant, the water-soluble vitamin E analogue Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), could, when added to the freezing extender in a split-sample design trial, improve the post-thaw viability and membrane quality of this particular portion of the ejaculate, with particular attention to the status of the plasma membrane. Using a split-sample design, the initial changes in the fluidity status of the sperm plasmalemma after thawing were measured by flow cytometry (FC) after loading with Merocyanine-540 and YO-PRO-1. The FC-derived data revealed a clear ejaculate portion-dependent effect of the antioxidant supplementation. While no beneficial effect of the antioxidant supplementation was visible in spermatozoa from portion I, more spermatozoa with intact membranes were observed in the supplemented samples of portion II, suggesting the protective effect of vitamin E is dependent of the portion of the boar ejaculate considered.

Animals↗

Ejaculate disruption in two species of voles (Microtus): on the PEI matching law.

We permitted male prairie and montane voles (Microtus ochrogaster and M. montanus) five thrusts, without ejaculation, with a female at variable times after a 1st male ejaculated. In both prairie and montane voles, there were fewer sperm, in relation to control conditions, in the female's tract 1 hr after ejaculation if the female received thrusts immediately or 15 min after the ejaculate. There was no such effect after a 50-min delay. There was no significant decrease in litter production in prairie voles caused by thrusts delivered either immediately or after a 15-min delay. Sperm transport in these species is susceptible to disruption for a longer period than in deer mice or rats. The proposal that the postejaculatory interval protects a male from disrupting its own sperm transport (the PEI matching law) appears not to hold for these species.

Animals↗