Showing papers in "Journal of Andrology in 1989"
TL;DR: There has been no recent effort to develop a prediction of fertility or fecundity based on sperm characteristics, and achievement of this goal may be elusive.
Abstract: This paper highlights the most critical aspects of the problem of predicting fertility. To determine if a laboratory test(s) is highly correlated with fertility it is essential to have: a) specific, precise and accurate laboratory tests, and b) precise and accurate fertility data. Acquisition of precise and accurate data for laboratory tests and fertility of spermatozoa in the same sample is not easy. Data derived from in vitro fertilization are not tests of fertility, because only a subset of the attributes important for fertilization in vivo are tested. Because of deficiencies in fertility data, there probably is no valid report for human spermatozoa correlating results of laboratory tests and fertility, and very few valid studies for laboratory or domesticated animals. There is little doubt that objective measures of sperm motion, acrosomal status, or other characteristics are significantly correlated with fertility. However, establishment of the correlations between a group of attributes and fertility is not the question of interest. The goal is prediction of fertility. There has been no recent effort to develop a prediction of fertility or fecundity based on sperm characteristics, and achievement of this goal may be elusive.
331 citations
TL;DR: Observations, which are the first to describe a biochemical defect in the spermatozoa of oligozoospermic patients, may carry significant implications for the etiology and treatment of this condition.
Abstract: The ability of human spermatozoa to exhibit sperm-oocyte fusion in response to the ionophore, A23187, was examined in relation to the capacity of these cells to generate reactive oxygen species. In 70 fertile control donors, there was an overwhelming pattern of high levels of sperm-oocyte fusion associated with low levels of reactive oxygen species production. By contrast, 88% of the 74 oligozoospermic patients exhibited less than 25% oocyte penetration in response to A23187 and 58% exhibited no penetration whatsoever. Of the 40 oligozoospermic patients who failed to respond to A23187, nine had low levels of reactive oxygen species production in association with impaired liquefaction of seminal plasma. Of the remainder, 17 (55%) exhibited defective sperm function together with elevated production of reactive oxygen species. These observations, which are the first to describe a biochemical defect in the spermatozoa of oligozoospermic patients, may carry significant implications for the etiology and treatment of this condition.
319 citations
TL;DR: It was concluded that non-SHBG-T serum levels, similar to serum total T levels, demonstrate a circadian pattern in young men and this circadian rhythmicity becomes blunted with normal aging.
Abstract: The circadian pattern in levels of serum total testosterone (T) in men becomes blunted with normal aging. However, because T not bound to sex hormone-binding globulin (non-SHBG-T) is felt to be a better representative of biologically available T than is total T, the possibility of a 24-h variation in non-SHBG-T in young men and the possibility that aging is associated with a blunting of that rhythm were investigated. Hourly blood samples were drawn on 10 normal young men (mean age 27.3 years) and 10 normal elderly men (mean age 70.7 years) over a 24-h period and the serum was assayed for total T, sex hormone-binding globulin (SHBG), and total protein; non-SHBG-T was calculated. SHBG was determined by radioimmunoassay as well as by a steroid-binding assay. Young men had a significantly higher (p less than 0.05) mean 24-h level of non-SHBG-T (1.91 +/- 0.62 nm/l) than did the elderly men (0.86 +/- 0.01 nM/l). Also, each young man showed a significant circadian rhythm in non-SHBG-T, with a group mean daily variation of 1.42 +/- 0.38 nM/l. In contrast, only 60% of the elderly men demonstrated a significant circadian rhythm in non-SHBG-T, and the group mean rhythm was blunted (maximum excursion 0.38 +/- 0.07 nM/l) compared with that of the young men. SHBG and total protein levels demonstrated similar 24-h variations in the two age groups. It was concluded that non-SHBG-T serum levels, similar to serum total T levels, demonstrate a circadian pattern in young men and this circadian rhythmicity becomes blunted with normal aging.
215 citations
TL;DR: Preliminary experiments indicate that the average sperm acrosin activity of ejaculates whose spermatozoa successfully fertilize human eggs in vitro is significantly higher than those that do not fertilize eggs.
Abstract: Acrosin, a sperm-specific acrosomal proteinase, has an essential role in the fertilization process. Low levels of acrosin appear to be associated with subfertility and infertility, and the acrosin activity of spermatozoa may potentially be a useful indicator of semen quality. The standard acrosin tests employed by research laboratories are too complicated and/or time consuming for clinical use; therefore, a simple assay has been developed to assess total acrosin activity (acrosin and activatable proacrosin). To perform the test, liquefied semen is centrifuged over Ficoll, the washed sperm pellet is suspended in a detergent (Triton X-100)-substrate (N-alpha-benzoyl-DL-arginine p-nitroanilide) buffer, pH. 8.0, and the amidase activity is determined spectrophotometrically after a 3-hour incubation period. Amidase activity can be inhibited with benzamidine, indicating that the activity is primarily or entirely due to acrosin. The absence of detergent in the incubation medium results in greatly reduced activity. The assay is repeatable, linear with increasing sperm concentration, sensitive to a lower limit of 2 x 10(6) spermatozoa, and the results correspond to those obtained with a standard acrosin extraction and assay technique. Storage of ejaculates at 3 to 6 C or at 22 to 24 C for 24 hours does not affect the acrosin activity significantly but much higher temperatures can cause a loss of activity. Freezing ejaculates results in a large decrease in sperm acrosin activity. Leukocytes show minimal activity in the assay. Sperm populations prepared by a swim-up procedure average approximately a 2-fold higher acrosin activity than the original ejaculates. Preliminary experiments indicate that the average sperm acrosin activity of ejaculates whose spermatozoa successfully fertilize human eggs in vitro is significantly higher than those that do not fertilize eggs.
143 citations
TL;DR: Although in general the intra-technician variability was low, there were marked and clinically significant differences between observers when assessing the same semen sample, and Technicians should be recruited who have natural ability as observers.
Abstract: Intra- and inter-technician variability in assessing sperm motility by the methods recently advocated by the World Health Organization (WHO) were studied. The intra- and inter-technician variability in estimating sperm concentration and the intra-technician variability in assessing sperm morphology were also examined. Intra-technician variability in assessing sperm motility appeared to be related to the natural ability and/or training of the observer. Although in general the intra-technician variability was low, there were marked and clinically significant differences between observers when assessing the same semen sample. There was no significant difference between observers in the assessment of sperm concentration, and intra-technician variability was low. When assessing sperm morphology, the intra-technician variability was potentially large (above a level of 20% morphologically ideal spermatozoa). Technicians should be recruited who have natural ability as observers. Quality control appears to be an essential exercise for any center that plans to relate semen parameters to fertility outcome.
107 citations
TL;DR: The data suggest that chronic administration of testolactone at this dose fails to maintain aromatase inhibition despite depression of 17,20-desmolase activity with elevated 17 alpha-hydroxyprogesterone and depressed SHBG binding capacity with elevation of free testosterone.
Abstract: The hypothesis that increased estradiol production may be the cause of impaired spermatogenesis in infertile men with idiopathic oligozoospermia was tested by administering the aromatase inhibitor, testolactone, and by assessing its effects on sperm output and fertility Our study was a randomized, placebo-controlled double-blind crossover trial Subjects (n = 25) with infertility due to unexplained oligozoospermia were given testolactone (2 g/day) or placebo for 8 months followed by crossover to the other treatment for an additional 8 months Total estradiol and testosterone levels during testolactone exposure did not change from basal and placebo values However, sex hormone-binding globulin binding capacity consistently decreased (30%, p less than 001) and free testosterone levels increased (36%, p less than 001) Free estradiol values increased but not significantly Additionally, LH and FSH serum levels increased by 15% and 20%, respectively (p less than 005), and 17 alpha-hydroxyprogesterone values increased by 90% (p less than 005) during drug administration Sperm output and semen quality remained unchanged during either testolactone or placebo treatment, and no pregnancies occurred during the 16-month study These data suggest that chronic administration of testolactone at this dose fails to maintain aromatase inhibition despite depression of 17,20-desmolase activity with elevated 17 alpha-hydroxyprogesterone and depressed SHBG binding capacity with elevation of free testosterone Testolactone is not efficacious in the treatment of idiopathic oligozoospermic infertility
90 citations
TL;DR: The ability of TNF alpha to cause a significant reduction of sperm motility in vitro suggests that this may be a mechanism for the infertility observed in women with minimal endometriosis.
Abstract: Tumor necrosis factor (TNF alpha) is present in elevated levels in peritoneal fluid from infertile women with endometriosis. The effect of TNF alpha on human sperm motility in vitro was evaluated utilizing peritoneal fluid from infertile women with minimal endometriosis containing 0, 100, 400, or 800 U of TNF alpha/ml as well as similar concentrations of recombinant human TNF alpha. No reduction in progressive and total motility was found at recombinant TNF alpha concentrations of 100 U ml. However, 500 and 1000 U of recombinant TNF alpha/ml caused a significant reduction in progressive and total sperm motility after 4 and 21 hours of incubation when compared with controls. Similarly, peritoneal fluid containing 100 U of TNF alpha/ml did not significantly reduce progressive and total sperm motility after either 4 or 21 hours of incubation; but peritoneal fluid containing 400 U of TNF alpha/ml reduced progressive sperm motility after 4 and 21 hours and total sperm motility after 21 hours of incubation. Peritoneal fluid with a TNF alpha concentration of 800 U/ml caused a significant reduction in both progressive and total sperm motility after 4 and 21 hours when compared with controls of TNF alpha-negative peritoneal fluid. The addition of polyclonal rabbit anti-TNF alpha antibody or 30-min heat inactivation at 56 C of TNF alpha-positive peritoneal fluid reversed the inhibitory effect on sperm motility. The ability of TNF alpha to cause a significant reduction of sperm motility in vitro suggests that this may be a mechanism for the infertility observed in women with minimal endometriosis.
84 citations
TL;DR: A synchronous acrosome reaction system was established for human spermatozoa and Ionomycin, a more specific calcium ionophore than A23187, produced essentially the same results but tended to decrease sperm motility.
Abstract: A synchronous acrosome reaction system was established for human spermatozoa. Seminal plasma is removed from the spermatozoa by centrifugation and the washed spermatozoa are capacitated in a modified BWW medium (without exogenous substrates) containing 35 mg/ml human serum albumin for 3 h at 37 C. Subsequently, 10 microM ionophore A23187 (final concentration) is added, the mixture incubated for 15 min at 37 C and the percent acrosome reaction determined by a modified triple stain technique (trypan blue stain omitted). Since no significant decrease in sperm motility occurs during incubation or after ionophore treatment, a vital stain does not need to be employed, allowing the use of any acrosome detection technique. The average percentage of acrosome-rejected spermatozoa after ionophore treatment (40 +/- 10%) was about 2- to 3-fold higher than that seen without ionophore treatment. Ionophore treatment for 15 min failed to stimulate the acrosome reaction in spermatozoa incubated for less than 3 h. Additionally, the presence of substrates in the BWW medium, higher sperm numbers, increased ionophore concentrations or longer incubation periods did not enhance the induction of the acrosome reaction. Ionomycin, a more specific calcium ionophore than A23187, produced essentially the same results as A23187 but tended to decrease sperm motility. This synchronous acrosome reaction system for human spermatozoa is relatively simple and can be used to study the effect of modulators on capacitation and/or the acrosome reaction.
82 citations
TL;DR: While all three steroids appeared to be good markers of systemic 5 alpha-reductase inhibition, further research will be needed to determine which steroid best reflects tissue DHT levels in patients receiving these inhibitors.
Abstract: To determine the hormonal effects of MK-906, an orally active 5 alpha-reductase inhibitor, on serum androgens and androgen conjugates, 12 healthy men were given 10, 20, 50, and 100 mg MK-906 2 weeks apart in randomized order in a 4-period crossover design. Serum testosterone (T), dihydrotestosterone (DHT), androstanediol glucuronide, and androsterone glucuronide were measured before and 24 hours after each dose. The effect of MK-906 on glucuronyl transferase activity, the enzyme responsible for androstanediol glucuronide and androsterone glucuronide formation, was assessed in vitro using rat prostate tissue. Serum T levels were unchanged after all doses. Serum DHT, androstanediol glucuronide, and androsterone glucuronide were suppressed by 70, 40, and 56%, respectively, after the 10-mg dose, and by 82, 52, and 66% after the 100-mg dose (P less than 0.02 for the comparison between the 10 and 100-mg doses for all three steroids), respectively. Baseline serum T and DHT levels were strongly correlated (R = 0.89, P = 0.0002), as were androstanediol glucuronide and androsterone glucuronide levels (R = 0.78, P = 0.003), but there was no correlation between DHT levels and the levels of either conjugated steroid. MK-906 had no effect on glucuronyl transferase activity in vitro. It was concluded that single doses of MK-906 suppress both conjugated and unconjugated 5 alpha-reduced androgens. While all three steroids appeared to be good markers of systemic 5 alpha-reductase inhibition, further research will be needed to determine which steroid best reflects tissue DHT levels in patients receiving these inhibitors.
76 citations
TL;DR: Increased daily production of cortisol is suggested as a possible mechanism underlying the elevated serum cortisol concentrations in chronic alcoholics during acute abstinence and this abnormality is shown to be reversible with sustained abstinence from alcohol.
Abstract: Pulsatile and circadian patterns of cortisol secretion during acute (3 to 16 days) and chronic (29 to 39 days) abstinence were examined in alcoholic men with no clinical or laboratory evidence of hepatic dysfunction or nutritional deficiencies. Mean and integrated 24-hour serum concentrations of cortisol determined by sampling the blood every 20 minutes over a 24-hour period were increased in six out of 10 alcoholic subjects during acute abstinence when compared with normal controls. Sustained abstinence in seven subjects with follow-up studies caused significant decreases in the mean maximal cortisol peak amplitude (13 +/- 1.0 SEM acutely vs. 10.3 +/- 0.52 micrograms/dl follow-up; P = 0.01), mean 24-hour serum cortisol concentrations (10.9 micrograms/dl +/- 1.2 vs. 8.5 micrograms/dl +/- 0.26; P = 0.047), interpulse valley mean (9.3 micrograms/dl +/- 0.88 vs. 6.5 micrograms/dl +/- 0.34; P = 0.007), and valley nadir (7.9 micrograms/dl +/- 0.69 vs. 5.4 micrograms/dl +/- 0.30; P = 0.0036) concentrations. Cortisol pulse frequency was normal. Although circadian cortisol rhythmicity was maintained in alcoholics, the timing of the circadian acrophase was delayed significantly (P = 0.006) during acute abstinence (1022 [clocktime] +/- 34 min) as compared with normal controls (0743 [clocktime] +/- 34 min), and the amplitude of circadian cortisol rhythms exceeded normal in five of 10 alcoholics. Analysis of data in one alcoholic subject by a new multiparameter deconvolution method demonstrated increases in secretory burst amplitude (0.64 microgram/dl +/- 0.08 SD), mass of cortisol released per burst (9.8 micrograms/dl +/- 1.2 SD), and daily endogenous cortisol production rate (22 mg +/- 2.4 SD) during acute abstinence. These values were statistically different when compared with seven normal controls and the subjects' values during sustained abstinence (P less than 0.02). In conclusion, the results of the present study suggest increased daily production of cortisol as a possible mechanism underlying the elevated serum cortisol concentrations in chronic alcoholics during acute abstinence. This abnormality is shown to be reversible with sustained abstinence from alcohol.
76 citations
TL;DR: The data suggest that these two complementary techniques represent an improvement in basic and/or clinical assessment of the functional spermatozoa status.
Abstract: Current evaluation of male fertility, routinely estimated by sperm count, motility, and morphology, provides only crude information about the fertility state of individuals. Both flow and image cytometry were applied to mitochondrial activity and sperm motility respectively. Sperm samples from fertile donors were concomitantly measured for Rhodamine 123 (Rh123) uptake (an estimation of mitochondrial activity), percentage of dead cells, and motility characteristics, such as percentage of motility, curvilinear velocity, and amplitude of lateral head displacement. These measurements were done under experimental conditions known to modulate sperm motility (temperature and time course survival in a capacitating medium). Bimodal distributions were found for Rh123 uptake. Flow cytometry-derived parameters were essentially time-dependent whereas motility characteristics were primarily temperature-dependent. Correlations were found between various flow cytometry-derived parameters and motility characteristics. Most of the correlations were obtained after a 24 h incubation in a capacitating medium. The most significant correlation in every experimental condition concerned the percentage of motile spermatozoa and the Rh123 uptakes. The drop in motility observed after a 24 h incubation was paralleled by a markedly lower drop in mitochondrial activity. The data suggest that these two complementary techniques represent an improvement in basic and/or clinical assessment of the functional spermatozoa status.
TL;DR: The power of several biochemical and physical markers was evaluated for their ability to discriminate between semen of infected and noninfected infertile men and the total output of citric acid had the strongest discriminating power.
Abstract: Infection of the male accessory sex glands may result in impaired secretory function and alteration of the composition of seminal plasma. Using receiver operating characteristic curves and accuracy tests, the power of several biochemical and physical markers was evaluated for their ability to discriminate between semen of infected and noninfected infertile men. The total output of citric acid had the strongest discriminating power, followed by acid phosphatase and gamma-glutamyltranspeptidase. Measurement of the concentration of fructose was found to be nondiscriminatory.
TL;DR: It is indicated that seminal vesicle-specific antigen, a group of predominant proteins in seminalvesicle fluid, is the structural component of seminal coagulum, and that prostate- specific antigen is the enzyme which digests seminal vedic antigen and liquifies semen coagula.
Abstract: Two-dimensional protein profiles of human semen, prostatic fluid, and seminal vesicle fluid were compared to demonstrate changes in the protein composition of human semen before and after liquefaction. Semen specimens were obtained from a volunteer. Prostatic fluid specimens were collected by rectal massage from patients visiting a urology clinic. Samples of seminal vesicle fluid were collected by needle aspiration from isolated seminal vesicles, which were removed at surgery. All specimens were prepared and processed according to the ISO-DALT system for separation of proteins in two-dimensional gels. Following electrophoresis, protein spots in the gels were visualized by silver staining. Prostatic fluid and seminal vesicle fluid showed their characteristic protein profiles. The protein profile of human semen contained specific proteins of both prostatic fluid and seminal vesicle fluid. One major group of proteins in seminal vesicle fluid (Mw 28,000-68,000 daltons), designated as seminal vesicle-specific antigen, was observed in freshly ejaculated human semen, but disappeared from the two-dimensional profile when the ejaculate was allowed to stand at room temperature for 30 min. When prostatic fluid or prostate-specific antigen was mixed with seminal vesicle fluid and incubated at 37C for 30 min, the seminal vesicle-specific antigen also disappeared from the two-dimensional profiles. The findings indicate that seminal vesicle-specific antigen, a group of predominant proteins in seminal vesicle fluid, is the structural component of seminal coagulum, and that prostate-specific antigen is the enzyme which digests seminal vesicle-specific antigen and liquifies semen coagulum.
TL;DR: Administration of cocaine resulted in dose-related decreases in body weights, increases in locomotor activity, and decreases in estradiol levels, and the high dose of cocaine was associated with an increase in the percentage of spermatozoa with heads separated from tails.
Abstract: Cocaine hydrochloride (30, 15, or 0 mg/kg) was administered daily subcutaneously to male rats for a minimum of 72 days. Animals receiving the 15-mg/kg and 0-mg/kg doses were pair-fed with animals receiving the higher dose. A fourth group served as a nontreated ad libitum-fed control to assess the role of cocaine-associated decreases in food and water intake. Administration of cocaine resulted in dose-related decreases in body weights, increases in locomotor activity, and decreases in estradiol levels. The high dose of cocaine was also associated with an increase in the percentage of spermatozoa with heads separated from tails. Cocaine did not affect sexual behavior, relative weights of the testis or accessory organs, histology of the testis, number of implantations, resorptions, fetal or newborn weight of offspring, or offspring weight at 21 days of age but did result in hyperactivity and increased perseverance in a T maze.
TL;DR: Findings indicate that in male rats immobilization stress induced a dissociation in LH and FSH responses, and decreased testosterone while inhibin remained unaffected.
Abstract: Adult male Wistar rats were subjected to acute and chronic immobilization stress. Changes in plasma levels of LH, FSH and testosterone and in the content of testicular inhibin and testosterone were studied. Plasma LH levels decreased significantly in response to both acute and chronic stress. Significant decreases in plasma testosterone content were also observed after chronic stress. In contrast, plasma FSH and testicular bioassayable inhibin content did not change after acute or chronic stress. These findings indicate that in male rats immobilization stress induced a dissociation in LH and FSH responses, and decreased testosterone while inhibin remained unaffected.
TL;DR: Results show that proliferation and some differentiation of precursor cells along the Leydig cell lineage can occur independent of LH, but the final stages of the differentiation process require hCG stimulation.
Abstract: In hypophysectomized rats, 2 days after the administration of the cytotoxic drug ethane dimethyl sulphonate (EDS), the proliferative activity of Leydig cell precursors increased six-fold. Thus, factors other than LH act locally to stimulate the proliferation of precursor cells after EDS. Twenty-six days after EDS administration, neither cells with the morphological characteristics of Leydig cells nor histochemical enzyme activities, such as 3 beta-HSD and alpha-naphtyl esterase, could be detected in testis tissue. In hypophysectomized rats treated daily with hCG (100 iu) for 7 days, starting at 26 days after EDS, the number of Leydig cells was increased to 48 +/- 11 cells (per 1000 Sertoli cells), which is approximately 4.5% of the intact control level. 3 beta-HSD and alpha-naphtyl esterase activity could be detected, and plasma testosterone levels had increased 15-fold compared with the hypophysectomized controls. These results show that proliferation and some differentiation of precursor cells along the Leydig cell lineage can occur independent of LH, but the final stages of the differentiation process require hCG stimulation.
TL;DR: The results indicate that the increase in mast cell numbers was estrogen-dependent, specifically related to the testis and did not seem to be a consequence of the increased in the connective interstitial tissue.
Abstract: Mast cells in the testis of control adult rats were found almost exclusively around subcapsular blood vessels. Discrete mast cells were distributed throughout the stroma of the epididymis and sex accessory glands. In neonatally estrogen-treated rats, a greater number of mast cells was present in the testicular interstitium, whereas no significant increase in the number of mast cells per square millimeter of stroma was found for the epididymis and sex accessory glands, despite stromal proliferation. On the other hand, androgen-treated rats did not have increased mast cell numbers in any organ. These results indicate that the increase in mast cell numbers was estrogen-dependent, specifically related to the testis and did not seem to be a consequence of the increase in the connective interstitial tissue.
TL;DR: Findings indicate that the postnatal development of the blood-epididymis barrier is gradual, and that its formation is virtually completed by Day 21.
Abstract: The development of the blood-epididymis barrier in immature rats (8, 11, 14, 18, and 21 days old) was examined with an electron microscope using lanthanum nitrate as an electron dense tracer. A gradual increase in the development of the blood-epididymis barrier was noted with age. On Day 8, lanthanum was frequently detected in both the intercellular spaces and the lumen. On day 14, no lanthanum penetration into the lumen was observed in 75% of the junctions in the caput, 40.3% in corpus, and 30% in cauda epididymidis. On Day 18, only 7.5%, 9%, and 15%, of the junctions in the caput, corpus, and cauda epididymidis, respectively, remained permeable to lanthanum. No lanthanum was observed in the lumen of any tubules in the 21-day-old rat epididymis. These findings indicate that the postnatal development of the blood-epididymis barrier is gradual, and that its formation is virtually completed by Day 21. As with adult rats, the zonula occludens is the ultimate structural component of the blood-epididymis barrier in immature rats (Agarwal and Hoffer, 1985).
TL;DR: The present study was designed to evaluate the automated analysis of rat sperm motility characteristics following subchronic administration of epichlorohydrin to validate the inclusion of sperm motion measurements in the process of reproductive risk assessment.
Abstract: The automated analysis of sperm motion endpoints is potentially useful in identifying male reproductive toxicants and ultimately in predicting fertility in humans. The present study was designed to evaluate the automated analysis of rat sperm motility characteristics following subchronic administration of epichlorohydrin. This type of validation is a prerequisite for inclusion of sperm motion measurements in the process of reproductive risk assessment. In the present studies videotapes were made of cauda epididymal spermatozoa from Long-Evans rats, both untreated and treated with epichlorohydrin. From analysis of videotapes of control epididymal spermatozoa, the relationship of various sperm motion endpoints and settings of the CellSoft computer-assisted sperm motion analysis system (Cryo Resources, Ltd., New York, NY) is described. Optimal settings of the system for analysis of rat spermatozoa are detailed. Employing data from both control and epichlorohydrin-treated animals, a statistical methodology is described that evaluates: (1) the distributions of CellSoft generated sperm motion endpoints, (2) the correlations between these endpoints, and (3) techniques for detection of dose-related effects.
TL;DR: Fertilization experiments using zona-free hamster eggs and spermatozoa from both guinea pig and human suggest that cytochalasin D may be an inhibitor of some fertilization processes such as sperm penetration or sperm head decondensation.
Abstract: Fertilization experiments using zona-free hamster eggs and spermatozoa from both guinea pig and human were conducted in the presence of cytochalasin D to evaluate the possible role of actin filaments in fertilization processes. When the actin filament inhibitor, cytochalasin D, was added to fertilization media at concentrations of 10 to 30 microM, penetration of eggs was significantly inhibited. Preincubation of the eggs with cytochalasin D and washing prior to addition of spermatozoa had no effect on penetration as quantitated by the number of swollen heads in the egg cytoplasm. However, spermatozoa preincubated with cytochalasin D and subsequently washed prior to egg addition showed reduced penetration of the same magnitude as when spermatozoa and eggs were coincubated with cytochalasin D. Both the percentage of zona-free eggs showing decondensed sperm heads and the penetration indices (total decondensed spermatozoa/total eggs) were significantly affected when spermatozoa were exposed to cytochalasin D. The DMSO vehicle used to dissolve cytochalasin D had little effect on the number of decondensed heads. When the concentration of cytochalasin D was increased (DMSO remaining constant) in human sperm experiments, percent penetration decreased and progressively fewer decondensed spermatozoa were recorded, indicating dose-responsiveness to cytochalasin D. Motility parameters of human spermatozoa were not altered at any of the concentrations of cytochalasin D tested. Neither guinea pig sperm motility nor acrosome reaction was altered significantly by cytochalasin D or the DMSO vehicle. These experiments suggest that cytochalasin D may be an inhibitor of some fertilization processes such as sperm penetration or sperm head decondensation.
TL;DR: Fifty-one patients with obstructive azoospermia caused by blockage at the caput epididymidis have been followed for 4 years after undergoing "specific tubule" vasoepididymostomy, bypassing the corpus and cauda, and there was a strong correlation with sperm motility.
Abstract: Fifty-one patients with obstructive azoospermia caused by blockage at the caput epididymidis have been followed for 4 years after undergoing "specific tubule" vasoepididymostomy, bypassing the corpus and cauda. The patency rate was 73%, and the pregnancy rate was 31%. There was no correlation between sperm count and pregnancy rate, but there was a strong correlation with sperm motility. With less than 20% motility, only 15% of the patients became pregnant, but with greater than 20% motility postoperatively, 58% became pregnant. If the wife was over 30 years old, only 21% got pregnant. If the wife was under 30, 67% got pregnant. "Redo" cases were just as likely to succeed as "first-time" attempts. In the "patent" cases, 43% of patients with spermatozoa that never reached or traversed the corpus or cauda epididymidis produced a pregnancy. Spermatozoa from the proximal caput produced a 33% pregnancy rate, whereas spermatozoa from the distal caput produced a 50% pregnancy rate. One-half of the pregnancies occurred more than 2 years postoperatively.
TL;DR: Preliminary data suggest that computer image analysis of sperm movement characteristics and differential evaluation of hypoosmotic sperm tail swelling might be useful for the prediction of human sperm fertility.
Abstract: Multivariate discriminant analysis was used to evaluate the usefulness of computer image analysis of sperm movement characteristics and differential patterns of sperm tail swelling after hypoosmotic treatment for predicting the human sperm in vitro fertilizing capacity assessed by the zona-free hamster egg penetration assay. Fifty-five semen samples, mostly normospermic, from untreated infertility clinic patients were analyzed. The % normal sperm morphology, linearity of seminal sperm movement, seminal sperm head beat frequency, mean and maximum amplitudes of lateral head displacement, and hypoosmotic sperm tail swelling patterns c, d and f were selected by multivariate discriminant analysis to be capable of discriminating the samples exhibiting the presence or the absence of sperm in vitro fertilizing capacity. The % total sperm tail swelling did not give additional information about in vitro fertilizing capacity. These preliminary data suggest that computer image analysis of sperm movement characteristics and differential evaluation of hypoosmotic sperm tail swelling might be useful for the prediction of human sperm fertility. Further prospective studies are necessary to validate their predictive functions.
TL;DR: Assessment of NPTR in normal men using a portable, take-home monitor found that penile tumescence time was found to decrease with advancing age, whereas the number of erectile episodes and penile rigidity did not significantly change with age for men in the third through sixth decades.
Abstract: Current methods now permit the measurement of nocturnal penile tumescence and rigidity (NPTR) in men with erectile dysfunction. But the relationship of rigidity to tumescence and the changes in rigidity with age have not been defined in normal men. Accordingly, the authors assessed NPTR in 47 normal men using a portable, take-home monitor (Rigiscan). Penile tumescence time was found to decrease with advancing age (p less than 0.05), whereas the number of erectile episodes and penile rigidity did not significantly change with age for men in the third through sixth decades (p less than 0.05). Using area-under-the-curve as an integrated measure of amplitude and duration, significant correlations between tumescence and rigidity (p less than 0.001), and between tip and base measurements (p less than 0.001) were found. With these normative data, prospective studies should determine the sensitivity and specificity of various NPTR parameters in the diagnosis of erectile dysfunction.
TL;DR: The data suggest that lumen diameter may be regulated by elongated spermatids, especially at stages VII and VIII.
Abstract: Adult male rats were treated with a single dose of 650 mg/kg methoxy acetic acid to deplete the seminiferous tubules specifically of pachytene and later spermatocytes. The effect of this treatment and the subsequent maturation-depletion of later germ cell types on the diameter of the seminiferous tubule and its lumen and the area of the seminiferous epithelium were studied in relation to the stages of the spermatogenic cycle. At 21 days after methoxy acetic acid treatment, the diameter of the tubule and the area of the epithelium were reduced below control values at all stages, consistent with the reduced number of early (stage VIII) or late (all other stages) spermatids. Unexpectedly, diameter of the lumen was also reduced at all stages other than VIII, and especially at stage VII. In controls, lumen diameter at stages VII and VIII was increased by approximately 50% compared with earlier and later stages. In rats treated 21 days previously with methoxy acetic acid no change occurred at stage VII (lacking elongated spermatids) while a normal increase did occur at stage VIII (lacking round but not elongated spermatids). At earlier times after methoxy acetic acid treatment when stage VII tubules were depleted of pachytene spermatocytes alone (3 days) or together with early spermatids (7 days), the diameter of the lumen was not significantly different from the control value. These data suggest that lumen diameter may be regulated by elongated spermatids, especially at stages VII and VIII.
TL;DR: The present results indicate that GnRH agonist treatment achieves a blockade of sexual maturation and that following cessation of treatment, normal pituitary-gonadal functions resume, with apparently normal fertility and normal offspring.
Abstract: The GnRH agonist [D-Trp6, des-Gly-NH2(10)]GnRH ethylamide was administered to prepubertal male and female dogs daily for 23 months by subcutaneous injection. During GnRH agonist treatment, plasma steroid levels, namely dehydroepiandrosterone, androst-5-ene-3 beta-17 beta-diol, androstenedione, testosterone, dihydrotestosterone, 5 alpha-androstane-3 alpha, 17 beta-diol, 5 alpha-androstane, 3 beta, 17 beta-diol were markedly inhibited in male animals, whereas in female animals, the plasma concentration of DHEA and delta 5-diol were decreased. Within 2 months following cessation of therapy, all steroids increased to normal adult levels. Morphological studies reveal that treatment of male animals with the GnRH agonist is accompanied by a small volume of seminiferous tubules, Leydig cells, and prostate gland, whereas in the ovaries of female animals, there is a large number of primordial follicles, a few primary follicles, but no secondary follicles. In the pituitary gland of animals of both sexes, LH-secreting cells have high levels of glycogen particles in their cytoplasm and tend to be either of normal appearance with dilated rough endoplasmic reticulum (RER) or strongly atrophied with a dark-stained cytoplasm, a contraction of RER, and a decrease in the number of secretory granules. Reticular cells of the connective tissue also show high levels of glycogen particles. After the 14 month recovery period, spermatogenesis has a normal adult appearance, the prostate gland shows a normal secretory epithelium, and secondary follicles are easily observed in the ovary. Gonadotrophs are free of glycogen accumulation, but reticular cells continue to show an accumulation of glycogen particles in their cytoplasm. Two male and two female animals were mated after the recovery period and produced normal offspring with normal fertility. The present results indicate that GnRH agonist treatment achieves a blockade of sexual maturation and that following cessation of treatment, normal pituitary-gonadal functions resume, with apparently normal fertility and normal offspring.
TL;DR: Findings indicate that depot delivery systems are a convenient way to administer GnRH analogs for sustained treatment schedules and are consistent with the hypothesis that this compound affects both the anterior pituitary gland and the testis.
Abstract: A sustained-release formulation of a potent gonadotropin-releasing hormone (GnRH) agonist, Zoladex (D-Ser(But),6 Aza Gly10-GnRH; ICI 118,630; goserelin), was administered subcutaneously (3.6 mg/depot) to male rats once every 28 days for 2-24 wk to determine the extent to which pituitary-testis function could be suppressed and whether suppression was maintained throughout the period of treatment. Administration of Zoladex resulted in sustained decreases in weight of the testis, epididymis, seminal vesicles and prostate gland. The decreases were apparent within 2 wk of initiating treatment. Patchy degeneration of the seminiferous tubules and atrophy of the Leydig cells were observed, but did not progress beyond the degree observed after 1 month of treatment. Serum and testis testosterone were markedly depressed after 2 wk of treatment, as was testis [125I]hCG binding. Serum gonadotropins were also reduced by treatment. Serum androgen binding protein (ABP) was elevated, testis ABP content remained unchanged, and epididymal ABP content was reduced. The changes are consistent with the hypothesis that this compound affects both the anterior pituitary gland and the testis. These findings indicate that depot delivery systems are a convenient way to administer GnRH analogs for sustained treatment schedules.
TL;DR: It was concluded that calcitonin stimulates cAMP formation and testosterone secretion, and increases the concentration of sex steroid receptors.
Abstract: Studies demonstrating calcitonin receptors on Leydig cells have suggested that these cells may be one of the many sites affected by this peptide. To investigate this possibility, the effect of synthetic salmon calcitonin on the TM3 Leydig cell line (derived from immature mouse Leydig cells) and on primary Leydig cell-enriched preparations was examined. Synthetic salmon calcitonin stimulated the conversion of [3H]adenine to [3H]cyclic AMP in TM3 cells. In addition, the hormone stimulated the basal secretion of testosterone in both TM3 cell- and Leydig cell-enriched cultures and potentiated the action of hCG on Leydig cell-enriched cultures. Synthetic salmon calcitonin also increased the concentration of androgen and estrogen receptors in cultured TM3 Leydig cells by 2- and 4-fold, respectively, when added to the culture medium (1 micrograms/ml). The fact that 8-bromo-cyclic AMP decreased both androgen and estrogen receptor concentrations suggested that the effect of calcitonin on sex steroid receptors is not mediated by its effect on cyclic AMP in these cells. The possibility that the action of calcitonin on steroid receptors might be mediated by another messenger such as calcium (Ca2+) was therefore considered. Progressively lowering the concentration of Ca2+ in the culture medium of the cells from 1.5 mM to less than 0.01 mM decreased the concentration of both androgen and estrogen receptors. Returning the Ca2+ concentration to normal levels (1.5 mM) restored steroid receptor levels. Receptor levels were also decreased when the extracellular Ca2+ concentration was lowered to 0.5 mM, and treatment with the Ca2+ ionophore, A23187 (1 microM), restored receptor levels to normal. The calcium channel blocker, verapamil, decreased the androgen receptor concentration but unexpectedly increased the concentration of estrogen receptors. It was concluded that calcitonin stimulates cAMP formation and testosterone secretion, and increases the concentration of sex steroid receptors. These observations provide evidence that the previously demonstrated calcitonin receptors on Leydig cells may be coupled to several biologic responses in this cell type.
TL;DR: Spermatozoa in the semen of vasectomized men were reported in 62 of 63 specimens from 24 men 2 to 31 years postvasectomy, and microrecanalization provides morphologic and physiologic bases for the protection of the testis and maintenance of spermatogenesis in man after vasectomy.
Abstract: Previously spermatozoa in the semen of vasectomized men were reported in 62 of 63 specimens from 24 men 2-31 years postvasectomy. A morphologic basis and term "microrecanalization" was proposed for this observation. Serial sections (5 mc at 200 mc intervals) of 40 specimens removed at vasovasostomy from 20 men (2-14 years postvasectomy) were examined and microcanals (small epithelial-lined channels) were demonstrated in 27 specimens from 18 men. In 9 of 27 specimens spermatozoa or sperm heads were found within the microcanals. Microcanals occurred in smooth muscle connective tissue and scar tissue in each segment testicular central and abdominal in the presence or absence of the vas deferens. Microcanal continuity was traced for 200-1140 microcons by computerized image analysis. Microrecanalization is characterized by the absence of inflammation or sperm extravasation and is histologically distinct from vasitis nodes of sperm granuloma. Microrecanalization provides morphologic and physiologic bases for the protection of the testis and maintenance of spermatogenesis in man after vasectomy. (authors)
TL;DR: The review has four objectives: to summarize studies of gene mutations that induce infertility in male mice, provide useful references to the literature about gene mutations affecting male mouse fertility, and present a summary of selected data collected from mice representing 21 mouse strains.
Abstract: The review has four objectives. The first objective is to summarize our studies of gene mutations that induce infertility in male mice. The second objective is to stress the power of mouse genetics and its application to male reproductive biology. The third objective is to provide useful references to the literature about gene mutations affecting male mouse fertility. Our goal is to cite references that can be used as a starting point for reading, not to present a comprehensive list of references. The fourth objective is to present a summary of selected data collected from mice representing 21 mouse strains.
TL;DR: Overall, no negative influence of indomethacin or oxaprozin treatment on male reproductive function could be found in healthy volunteers.
Abstract: To evaluate the influence of indomethacin and oxaprozin on reproductive function in healthy young men, 34 volunteers with normal semen parameters were recruited. In a randomized double-blind design, 12 men were treated with placebo, 12 received 600 mg/day of oxaprozin and 10 took indomethacin 25 mg t.i.d. This treatment phase lasted for 14 days after which a follow-up period extended for another 10 weeks. Sperm counts, percentage of motile and normally formed sperm cells, sperm velocity, linearity, lateral head displacement and beat frequency were evaluated by computerized image analysis once before treatment and at weekly intervals during the rest of the study. Prostaglandin levels in seminal plasma were significantly reduced after 2 weeks of treatment and remained suppressed for at least 2 additional weeks. In spite of this long lasting impairment of physiologic prostaglandin concentrations, no changes in any of the measured parameters were detectable when compared with the placebo group. Basal levels of testosterone, estradiol, LH, FSH, TSH and prolactin were unchanged. The response of hypophyseal hormones to a combined GnRH/TRH test before, during and after the treatment also was not affected. Overall, no negative influence of indomethacin or oxaprozin treatment on male reproductive function could be found in healthy volunteers. Since the active treatment phase was only 14 days, one can only speculate about long term effects of the tested drugs on reproductive parameters in men.