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PubMed2000

Xenoesterogens and male infertility: myth or reality?

AIM: To evaluate the role of polychlorinated biphenyls (PCBs) as a potential environmental hazard in the deterioration of male fertility. METHODS: Fifty-three males were studied. After a thorough case history evaluation and relevant clinical and laboratory investigations, PCBs were estimated in the seminal plasma of 21 infertile men with "Unexplained Male Factor" and 32 fertile controls. Peak retention times of the eluants were compared with those of the commercially available standard PCB Mix, and the results confirmed spectrophotometrically. Seminal PCB concentrations were compared between i) fertile and infertile men and ii) men from different areas and diets. The relationship between PCB concentrations and measures of sperm quality such as the total motile sperm count, was assessed. RESULTS: PCBs were detected in seminal plasma of infertile men but absent from controls. Sperm quantity and quality were significantly lower in infertile men compared to controls. The highest average PCB concentrations were found in fish-eating urban dwellers, and followed in succession by fish-eating rural dwellers, non fish-eating urban dwellers and non fish-eating rural dwellers. The total motile sperm counts were inversely proportional to the PCB concentrations and were significantly lower than those of the respective controls. CONCLUSION: PCBs may be instrumental in the deterioration of sperm quantity and quality, a contaminated fish diet being the main source of exposure.

Adult↗
PubMed1996

Developmental exposure of male germ cells to 5-azacytidine results in abnormal preimplantation development in rats.

Methylation of cytosine residues in mammalian DNA is established during gametogenesis and embryogenesis; it plays an important role in gene regulation and normal embryonic development and has also been implicated in genomic imprinting. In the present study, we evaluated whether paternal administration of 5-azacytidine, a drug that is incorporated into DNA and blocks DNA methylation, could alter male germ cell development and function. A drug that does not block methylation, 6-azacytidine, served as a control. Adult male Sprague-Dawley rats (n = 4-8 per group) were treated i.p., three times per week for 4 and 11 wk, with saline or 2.5 (low dosage) or 5.0 (high dosage) mg/kg of 5-azacytidine and 6-azacytidine. After each of the treatment periods, males were mated to determine effects on fertility and embryo development. Although neither 6-azacytidine nor 4 wk of 5-azacytidine treatment affected male reproductive organ weights or sperm counts, 11 wk of 5-azacytidine resulted in dose-dependent reductions in testis and epididymal weights and sperm counts. Both dosages of 5-azacytidine resulted in significant increases in preimplantation loss, and the high dosage of 5-azacytidine caused a decrease in fertility. Examination of embryos on Day 2 of gestation revealed a striking dose-dependent increase in the average number of abnormal embryos per litter sired by the males treated with 5-azacytidine (saline, 0.33 +/- 0.24; low dosage, 2.64 +/- 0.92; high dosage, 10.09 +/- 0.95). In summary, paternal administration of 5-azacytidine interfered with normal male germ cell development and resulted in alterations in fertilization and early embryo development. We suggest that 5-azacytidine-induced alterations in germ cell DNA methylation patterns may be one of the underlying mechanisms, since similar dosages of the analogue 6-azacytidine had no effect on male reproduction and progeny outcome.

Animals↗
PubMed2006

Inhibin B is a better marker of spermatogenesis than other hormones in the evaluation of male factor infertility.

OBJECTIVE: To assess the role of inhibin B in the evaluation of male factor infertility. DESIGN: Prospective study. SETTING: Reproductive endocrinology clinic. PATIENT(S): Seventy-five patients with infertility problems (mean age 31.2 +/- 7.5 years) and 12 controls (32.1 +/- 8.8 years) with proven fertility. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen analysis was performed according to World Health Organization guidelines. Testicular volume was assessed with the Prader's orchidometer. Serum levels of inhibin B (pg/mL), LH (mIU/mL), FSH (mIU/mL), prolactin (micro IU/mL), and testosterone (nmol/L) were assessed. RESULT(S): The mean +/- SEM inhibin B and testosterone levels were significantly lower in the patients than in the controls (inhibin B: 116.4 +/- 11.7 vs. 181.2 +/- 20.9, P=.008; testosterone: 13.6 +/- 0.9 vs. 25.1 +/- 2.9, P=.008). In general, sperm count and testicular volume in the patients were significantly and positively correlated with inhibin B (sperm count: r = 0.476, P<.0001; testicular volume, right: r = 0.57, P=.0001; left: r = 0.53, P=.0001); the inhibin B-FSH index was negatively correlated with FSH. Inhibin B was more strongly correlated with testicular volume and semen parameters than FSH. Inhibin B in the patients was negatively correlated with FSH (r = -0.723, P=.0001) and LH (r = -0.52, P=.0001) and was positively correlated with testosterone (r = 0.4, P=.0013). CONCLUSION(S): Inhibin B measurement is a better marker of fertility status than FSH and LH. Concentration of inhibin B in patients with infertility may provide useful information on spermatogenesis and possibly serve as a more direct marker of spermatogenesis than FSH.

Adult↗
PubMed1986

Serum and semen zinc levels in normozoospermic and oligozoospermic men.

Zinc is necessary for growth, sexual maturation and reproduction. Because high concentrations of zinc are found in the male reproductive system, a relationship between zinc and male infertility has been suggested. We studied 11 unselected men who presented to a Reproductive Endocrinology Clinic with histories of infertility and low sperm counts. Reproductive hormones and semen and serum zinc levels were measured. All men had semen analyses performed on at least three separate occasions. A similar set of laboratory evaluations were performed on 11 other men who had normal semen analyses and no history of infertility. No abnormalities of reproductive hormones were found in either group. Mean serum zinc levels were significantly lower in the infertile men (p less than 0.05). Mean semen zinc levels were not significantly different. There was no correlation between serum and semen zinc levels in either group. A significant correlation was found between sperm count and semen zinc (r = 0.66, p less than 0.05) in the volunteers with normal counts, but not in the oligozoospermic men. The results obtained in this study suggest that lowered serum zinc is more common than formerly appreciated in unselected patients with infertility. The high level of zinc found in semen is due primarily to the secretions of the prostate gland and reflects prostatic stores. Serum zinc is thought to be a reasonable indicator of zinc status. The lack of correlation between serum zinc and semen zinc found in our study suggests that mild zinc deficiency may lower serum zinc while the larger prostatic zinc stores remain unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

[Clinical studies of spermatogenic damage in patients with testicular cancer].

We investigated the spermatogenic function of patients with testicular cancer, and the influences of anti-cancer chemotherapy on testicular function in these patients. Fifty-one patients with testicular cancer were selected for evaluation of their testicular function, including spermatogenesis and endocrinological function, before and after chemotherapy with anti-cancer agents. Before chemotherapy with anti-cancer agents, 22 of 49 patients (44.8%) had a sperm concentration of less than 20 x 10(6)/ml, and 8 patients (16.3%) showed azoospermia. The mean sperm concentration of the patients with testicular cancer was 29.0 x 10(6)/ml before therapeutic chemotherapy with anti-cancer agents, but within 3 months after chemotherapy, it decreased to 3.86 x 10(6)/ml (p < 0.01). Fifteen of 19 patients (73.7%) were revealed to have azoospermia. Damage to spermatogenesis became more severe with the number of chemotherapy treatment. No patients had a detectable sperm count at the completion of 3 or more courses of chemotherapy. But some patients who received 3 courses or more of chemotherapy showed recovered sperm counts after 2 or more years. Thus, a lack of sperm after chemotherapy for cancer did not necessarily indicate inability to recover spermatogenesis over 2 years after chemotherapy. Serum FSH levels of the patients were 5.62 +/- 3.43 mIU/ml before chemotherapy, and 19. 70 +/- 17.06 mIU/ml (p < 0.05) at the time of its completion. Serum FSH levels could reflect damage to spermatogenesis in these cases. Cases in which spermatogenesis did not recover may have higher serum FSH levels than those with recovery of spermatogenesis.

Adolescent↗
PubMed1997

Inhibin B in men with normal and disturbed spermatogenesis.

Inhibin, a dimeric gonadal glycoprotein, inhibits the production and/or secretion of follicle stimulating hormone (FSH). The major species currently recognized are inhibin A (alphabeta A subunit) and inhibin B (alphabeta B subunit). In men, inhibin B seems to be the physiologically important form of inhibin. Therefore we measured serum inhibin B using a new two-site immunoenzymatic assay in 14 men (mean +/- SEM age, 34.5 +/- 0.7 years) with sperm counts >20 x 10(6)/ ml, in 35 men (mean +/- SEM age, 36.4 +/- 1.3 years) with oligozoospermia (sperm count <20 x 10(6)/ml) and in men with azoospermia (three orchidectomized men, three men with Klinefelter's syndrome, 10 men with Kallmann's syndrome). We compared inhibin B concentrations with serum FSH and sperm concentrations. In men with normal sperm concentrations (44.7 +/- 6.4 x 10(6)/ml), the concentration of inhibin was 223 +/- 18 pg/ml and of FSH 5.0 +/- 0.7 IU/l; in patients with low sperm concentrations (3.7 +/- 0.8 x 10(6)/ml), the concentration of inhibin B was 107 +/- 12 pg/ml and of FSH 12.2 +/- 1.5 IU/l. In all patients, except those with hypogonadotrophic hypogonadism, the relationship between inhibin B and FSH concentrations was inverse (r = -0.69, P < 0.0001). In all patients the sperm concentration was positively correlated with inhibin B concentrations (r = 0.70, P < 0.0001) and negatively correlated with FSH concentrations (r = -0.37, P < 0.01). We conclude that inhibin B may be a marker of exocrine testicular function and could offer improved diagnosis and treatment modalities for male infertility.

Adult↗
PubMed1983

Effect of chronic administration of inhibin and testosterone on spermatogenesis in adult male rats.

Inhibin (Inh) and testosterone (T) were administered to adult male rats for 32 days to evaluate their effect on spermatogenesis. Fifty micrograms of Inh was injected subcutaneously twice daily, and T was administered as Silastic implants 2.5 cm in length. Weights of testes and epididymides were significantly decreased in (Inh + T)- and T-treated groups, but not in Inh-treated rats. Although Inh alone could suppress both the testicular and the epididymal sperm count, maximum suppression was observed in the (Inh + T)-treated group. The effect on the epididymal sperm count, however, was pronounced. The accessory organ weights remained unaffected in all treated groups. Chronic administration of Inh and T results in partial impairment of spermatogenesis.

Animals↗
PubMed1980

The effect of clomiphene citrate on different sperm parameters and serum hormone levels in preselected infertile men: a controlled double-blind cross-over study.

In order to try to clarify the often supposed stimulating effect of clomiphene citrate on spermatogenesis a controlled double-blind cross-over trial was used. 30 pre-selected normogonadotropic infertile men were given 50 mg clomiphene citrate daily or placebo in a double-blind cross-over fashion for three months, each treatment period being separated by three to four months. On clomiphene treatment the median sperm count increased from 13.3 to 28.7 mill/ml (P < 0.001). During the placebo treatment schedules the median sperm count remained unchanged (P < 0.05). The increases of FSH, LH, testosterone, and oestradiol were highly significant (P < 0.001) during the clomiphene treatment but during placebo treatment the median hormone levels did not change (P < 0.05). Three pregnancies occurred due to clomiphene treatment and one occurred during placebo treatment.

Adult↗
PubMed2006

Semen variables and hormone profiles after kidney transplantation during adolescence.

Our aim was to investigate the semen variables and hormone profiles among transplant patients who received kidneys during adolescence. Seven postpubertal transplant patients who underwent successful renal transplantation during adolescence (13-19 years; 3 were preemptive) were enrolled in our clinical follow-up. Serum levels of prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were checked together with the semen analysis. The ages of the patients ranged from 18 to 25 years (median, 22 years). The median age was 15 years (range, 12-18 years) at initial presentation. The median time between initial diagnosis and transplantation was 12 months (range, 2-60 months). The median follow-up after transplantation was 51 months (range, 23-134 months). Three of the seven patients had unilateral low testicular volume. The renal function tests were within normal limits, as well as serum levels of prolactin, FSH, LH, and testosterone. Sperm counts ranged from 0.2 to 55 million/mL (median, 1.7 million/mL). Only 1 patient (14.2%) had normal sperm parameters. Oligoteratozoospermia (low sperm count and defects in morphology) was observed in 1/7 (14.2%), asthenoteratozoospermia (low levels of motility and defects in morphology) in 1/7 (14.2%), and all parameters were abnormal in 4/7 (57.1%) cases. Our data suggest that in contrast to adult patients, semen variables are severely affected and spermatogenesis does not improve after renal transplantation when the patient was subjected to uremia before or during adolescence, the crucial period for spermatogenesis.

Adolescent↗
PubMed2003

A clinical trial of 7 alpha-methyl-19-nortestosterone implants for possible use as a long-acting contraceptive for men.

Several preparations of testosterone and its esters are being investigated alone or in combination with other gonadotropin-suppressing agents as possible antifertility agents for men. We studied the effectiveness of 7 alpha-methyl-19-nortestosterone (MENT) as an antispermatogenic agent in men. MENT has been shown to be more potent than testosterone and to be resistant to 5 alpha-reduction. For sustained delivery of MENT, we used a system consisting of ethylene vinyl acetate implants containing MENT acetate (Ac), administered subdermally. Thirty-five normal volunteers were recruited in 3 clinics and were randomly assigned to 1 of 3 doses: 1 (12 men), 2 (11 men), or 4 (12 men) MENT Ac implants. The initial average in vitro release rate of MENT Ac from each implant was approximately 400 micro g/day. Implants were inserted subdermally in the medial aspect of the upper arm under local anesthesia. The duration of treatment was initially designed to be 6 months. However, in 2 clinics the duration of treatment was extended to 9 months for the 2-implant group and to 12 months for the 4-implant group. Dose-related increases in serum MENT levels and decreases in testosterone, LH, and FSH levels were observed. Effects on sperm counts were also dose related. None of the subjects in the 1-implant group exhibited oligozoospermia (sperm count, <3 million/ml). Four subjects in the 2-implant group became oligozoospermic, 2 of whom reached azoospermia. Eight subjects in the 4-implant group reached azoospermia, with 1 exhibiting oligozoospermia, whereas 2 were nonresponders. Side effects generally seen with androgen administration, such as increases in erythrocyte count, hematocrit, and hemoglobin and a decrease in SHBG, were also seen in this study and were reversible. Changes in lipid parameters were moderate and transient. Liver enzymes showed small changes. This study demonstrates that MENT Ac, when administered in a sustained release fashion via subdermal implants, can inhibit spermatogenesis over a prolonged period after a single administration and has the potential to be used as a male contraceptive.

Adult↗
PubMed1993

[The significance of the "routine spermiogram". A critical analysis].

A spermiogram includes the determination of the sperm count (normal range 20-250 million/ml), the percentage of motile cells (> 50%) and the percentage of abnormal cells (< 60%). Male infertility is the most important indication for a spermiogram. The values for seminal parameters, however, show only a weak correlation with conception rates, even in the case of in vitro fertilization. This may be due to the wide variability of values in an individual man, but it is also likely that the aetiopathogenesis of infertility is not only determined by parameters that can be assessed microscopically, but in addition by functional parameters that have not yet been identified. The assumption that computer-assisted image analysis of motility and morphology (CASA) would improve the predictive power of seminal parameters has not been verified. However, the spermiogram is useful in therapeutic studies of male infertility. When the extent of relevant alterations is assessed the wide intraindividual variability must be borne in mind. Treatment cannot be assumed to have been successful unless the sperm count increases by more than 50% of the initial value. Side effects of drugs affecting spermatogenesis and recovery after cessation of therapy can be demonstrated by repeated spermiograms. Evidence of the effects of environmental factors can also be seen in the spermiogram, but distinct correlations are difficult to determine. Semen analysis continues to be used in the development of male contraceptives, but is no substitute for the measurement of conception rates.

Adolescent↗
PubMed2004

Progressive depletion of germ cells in a man with nonmosaic Klinefelter's syndrome: optimal time for sperm recovery.

We describe a sequential deteriorated change of sperm count in a 30-year-old infertile man with nonmosaic Klinefelter's syndrome. His initial semen analysis revealed oligozoospermia; however, the sperm count decreased progressively, which resulted in azoospermia over a period of 3 years. By testicular sperm extraction, a few spermatozoa were recovered. We analyzed the germ cells with three-color fluorescence in situ hybridization, and the presence of a 46,XY lineage was found. We suggest that progressive depletion of germ cells might occur in men with nonmosaic Klinefelter's syndrome and that these men should undergo semen cryopreservation or sperm recovery as early as possible.

Adult↗
PubMed1986

Post-treatment fertility in patients with testicular cancer. III. Influence of radiotherapy in seminoma patients.

Sperm analysis and serum hormone measurements (LH, FSH, testosterone) were performed in 29 patients after orchiectomy for seminoma before and after irradiation. Before radiotherapy 14 of 20 orchiectomized patients were azoospermic or had impaired spermatogenesis. A minimum sperm count was found 1 year after radiotherapy with gradual improvement up to 2 years. The recovery of sperm cell production was impaired most in patients with pre-treatment sperm counts less than 3 million/ml. Serum testosterone remained at low normal levels throughout the observation period. The mean serum FSH was increased 1 year after radiotherapy but returned to normal in 50% of patients within 3 years after treatment. This post-treatment increase in FSH was significantly correlated with increased pre-treatment FSH but not with the gonadal dose, which was 1 to 3% of the target dose. Severe disturbances in spermatogenesis, observed 2 to 3 years after radiotherapy for early seminoma, are likely to be the expression of a highly impaired pre-treatment sperm cell production and only to a lesser degree dependent on the irradiation of the remaining testicle.

Adult↗
PubMed2000

Vanadocene-mediated in vivo male germ cell apoptosis.

Vanadocenes are potent apoptosis-inducing cytotoxic agents against human testicular cancer cells in vitro. The present study investigated the ability of four vanadocenes-vanadocene diazide (VDA), vanadocene dicyanate (VDCN), vanadocene dioxycyanate (VDOCN), and vanadocene monochloro oxycyanate (VDCO)-to induce male germ cell apoptosis in vivo in mouse testes by repetitive intratesticular injection of vanadocenes (7.5 mg/kg/testis) for 28 days. Germ cell loss in vivo was measured by epididymal sperm count, testes weights, and histologic evaluation of the testes. Repetitive intratesticular injection of vanadocenes led to decreased sperm counts and reduced testicular weights. Histopathological examination revealed seminiferous tubular atrophy, inhibition of spermatogenesis, and the preferential loss of maturing and elongated spermatids. In situ evaluation by the terminal deoxynucleotidyl transferase-mediated FITC-deoxyuridine triphosphate nick-end labeling (TUNEL) of seminiferous tubule cross sections and laser confocal microscopy showed characteristic apoptotic cells identified primarily as pachytene spermatocytes delineating the periphery of the seminiferous tubules. The ability of vanadocenes to induce germ cell apoptosis in vivo may have potential utility in the treatment of testicular seminomas in humans.

Animals↗
PubMedDate not supplied

Higher testosterone dose impairs sperm suppression induced by a combined androgen-progestin regimen.

In this study we compared the effects of high-dose and low-dose testosterone enanthate (TE) administered with the same dose of cyproterone acetate (CPA). Eighteen men aged 21-45 were treated with CPA 5 mg/day and with TE 100 mg/week (n = 9; CPA-5-100) or TE 200 mg/week (n = 9; CPA-5-200) for 16 weeks. Semen analyses were performed every 2 weeks; physical examination and chemistry, hematology, gonadotropin, and testosterone measurements were performed every 4 weeks. At week 16 of treatment, sperm counts were significantly more suppressed in the CPA-5-100 group than in the CPA-5-200 group. Sperm counts returned to baseline in all subjects after hormone administration ceased. No difference in gonadotropin levels was found at any time between the 2 groups. During the treatment phase, testosterone levels were significantly higher in the CPA-5-200 group than in the CPA-5-100 group. The present study confirms that CPA/TE administration induces profound sperm suppression. An increase in the dose of androgen resulted in less profound sperm suppression despite no difference in gonadotropin suppression. These data suggest that high testosterone levels can maintain sperm production in men.

Adult↗
PubMedDate not supplied

Relationship between sperm cell ubiquinone and seminal parameters in subjects with and without varicocele.

In a previous paper it was demonstrated that Coenzyme Q10, a lipidic molecule with important antioxidant properties, is present at remarkable levels in human seminal fluid, and shows a direct correlation with seminal parameters (sperm count and motility). In patients with varicocele, on the contrary, correlation with sperm motility was lacking and a higher proportion of Coenzyme Q10 was found in seminal plasma. In the present study, the levels of Coenzyme Q10 in the cell pellet of spermatozoa, obtained after centrifugation of semen, were evaluated. In nonvaricocele subjects it was observed that a higher concentration of Coenzyme Q10 (expressed as ng of the molecule per million of cells) was present in the spermatozoa of oligospermic and asthenospermic patients (sperm count < 20 x 10(6) spermatozoa ml-1, sperm motility < 40%). This relationship was not observed in varicocele subjects, who also showed slightly lower intracellular absolute values of the conenzyme. Since Coenzyme Q10 is an antioxidant molecule involved in the defence of the cell from free radical damage, higher intracellular concentrations may represent a mechanism of protection of the spermatozoa. In varicocele patients, this mechanism could be deficient, leading to higher sensitivity to oxidative damage.

Adult↗
PubMed1993

Platelet-activating factor treatment of human spermatozoa enhances fertilization potential.

OBJECTIVE: The purpose of this study was to evaluate the effects of platelet-activating factor treatment on human spermatozoa fertilizing capability, as assessed by the zona-free hamster penetration assay. STUDY DESIGN: Twenty-three semen specimens were divided into two groups on the basis of initial motile sperm count greater or less than 20 x 10(6)/ml. Each sample served as its own treatment control. Twice-washed spermatozoa were treated with 1 x 10(-7) mol/L of platelet-activating factor before performing the sperm penetration assay. For the two groups the percent penetrations and penetration index were compared with the paired t test, and an independent t test was used to compare parameters between groups. RESULTS: Significant enhancement of both percent penetrations (p < 0.0001) and penetration index (p < 0.005) were noted on platelet-activating factor treatment in both groups. Enhancement of both indices were noted to be independent of initial motile sperm counts. CONCLUSION: Platelet-activating factor treatment of human spermatozoa may be of potential therapeutic value in certain cases of asthenospermia or fertilization failure in human in vitro fertilization.

Female↗
PubMedDate not supplied

Hormone load tests in infertile male patients.

The recognition that discreet hormonal abnormalities may cause ovulation disorders in women suggested that the male partner of infertile women might also suffer from unrecognized hormonal dysfunction amendable to substitution therapy. We obtained a combined stimulation test with gonadotropin-releasing hormone (GnRH), thyreotropin-releasing hormone (TRH), and ACTH in 225 males with childless spouses, when the couple sought to have children for at least one year. The following hormone levels were determined: estradiol (E), thyroid-stimulating hormone (TSH), prolactin, testosterone (T), dihydrotestosterone (DHT), androstenedione(A), 17-OH-pregnenolone (17-OH-Preg), 17-OH-progesterone (17-OHP), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), cortisone (F), and 21-desoxycortisone (21DF). Basal and stimulated, and adrenal-testicular steroids with and without ACTH stimulation failed to demonstrate a relevant relationship to semen parameters. Gonadotropin levels had a significant negative correlation to all important semen parameters (testicular volume, sperm count, motility, morphology, and vitality) and were positively correlated to spermiogenetic defects. Stimulated LH values were more clearly associated with spermiogenetic defects than basal LH. Nonetheless, basal FSH concentrations were more informative than LH. Stimulated prolactin values were positively correlated with both gonadotropin and with sperm morphology. E concentrations had a significant positive correlation with both basal and poststimulation DHEAS values, and showed a highly negative correlation with sperm count, morphology, and vitality. In comparison, good sperm parameters were associated with high poststimulation T concentrations. The results of this study suggest that basal FSH and E concentrations, as well as the stimulated LH, T, and prolactin determinations, should be included in the evaluation of male sterility.

Adrenal Cortex Hormones↗