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Reproductive toxicology of aluminum in male mice.

The reproductive toxicology of aluminum was studied in mice. Adult male mice were treated intraperitoneally with aluminum nitrate at doses of 0, 50, 100, and 200 mg/kg/day for 4 weeks before mating with untreated females. Decreased body weight was seen in all aluminum-treated groups. Decreased pregnancy rate was observed in the females mated with males previously treated with 100 or 200 mg/kg/day of aluminum nitrate. High-dose male mice showed significantly decreased testicular and epididymal weights, as well as significant decreases in testicular and spermatid counts and epididymal sperm counts. Spermatid counts were also reduced at 100 mg/kg/day. However, the sperm motility was unaffected, and the percentages of morphological normal spermatozoa in all mice exposed to aluminum were comparable to the values in control mice. Histological changes, including necrosis of spermatocytes/spermatids, were observed in the testes of male mice treated with 100 and 200 mg/kg/day of aluminum nitrate, whereas the tubular diameters were unaffected by aluminum administration. The current study demonstrates adverse effects of parenteral aluminum exposure on the mouse male reproductive system. The "no observable adverse effect level" (NOAEL) was 50 mg/kg/day.

Aluminum↗

ATP contents of human semen, seminal plasma and isolated sperm at time intervals after ejaculation.

1. ATP was estimated in 105 samples of human semen, seminal plasma and sperm of normozoospermic and oligozoospermic origins at time intervals after ejaculation. 2. In semen with sperm counts up to 40 millions per ml and in seminal plasma, ATP levels were lower than in specimens with higher sperm counts. 3. In isolated sperm, the ATP content decreased with the increase in sperm density. 4. The decrease in ATP after 24 hr was the highest in sperm, lower in semen and the lowest in seminal plasma, being maximal in specimens with high sperm counts.

Adenosine Triphosphate↗

Quantitative analysis of the seminiferous epithelium in human testicular biopsies, and the relation of spermatogenesis to sperm density.

Quantitative analysis of the seminiferous epithelium was performed in bilateral testicular biopsy specimens from 14 patients with sperm counts ranging from 0 to 89 million/ml. All Sertoli cells and germ cells within each seminiferous tubule cross-section were counted in all biopsies. Results were expressed either as number of cells per unit length of seminiferous tubule circumference or as number of cells per Sertoli cell. Results were correlated with sperm count (millions per milliliter), total sperm count (millions per ejaculate), and age. A significant correlation between sperm density and germ cell counts was demonstrated. Coefficients of correlation were higher when results were expressed per unit of tubular wall length than when expressed per Sertoli cell. In men with sperm counts below 5 million/ml the number of germ cells in the biopsy was lower than in men with higher sperm counts. Spermiogenesis appeared to be most affected. In this group of patients an adverse effect of age on spermatogenesis was noted.

Adolescent↗

Sperm morphology and chromatin condensation before and after semen processing.

Semen analysis constitutes the most important investigation of male infertility. However, the true anomalies present in defective sperm cells have been only partially characterized. The integrity of the sperm chromatin may play the most important role, particularly in ICSI, where most of the natural selection mechanisms are bypassed. This study was carried out to characterize sperm morphology (strict criteria), to evaluate chromatin condensation and sperm count in native semen as well as after semen preparation by the swim-up technique, and to eventually evaluate any correlation between these parameters. Semen from 90 men was analyzed for the above parameters in both the fresh and processed semen. Whereas the sperm count decreased after sperm preparation by the swim-up technique in comparison to the value in the fresh semen (p < .001), there was an increase in the percentage of morphologically normal (p < .001) and chromatin-condensed sperm (p = .99). However, there was no correlation between sperm morphology, chromatin condensation, and sperm count either in the fresh or in the processed semen samples. These results suggest that sperm morphology, sperm count, and chromatin condensation are independent parameters that should be evaluated separately in the assessment of male fertility in an assisted reproduction program.

Chromatin↗

Comparison of the sperm quality necessary for successful intrauterine insemination with World Health Organization threshold values for normal sperm.

OBJECTIVE: To compare World Health Organization threshold values for normal sperm with the initial sperm quality necessary for successful IUI. DESIGN: Retrospective study. SETTING: Private fertility clinic. PATIENT(S): One thousand eight hundred forty-one couples undergoing 4,056 cycles of IUI. INTERVENTION(S): Intrauterine insemination. MAIN OUTCOME MEASURE(S): Relation of initial sperm quality to fecundity. RESULT(S): Progressive motility and total motile sperm count were the initial sperm characteristics most closely related to pregnancy on discriminant analysis. The per-cycle pregnancy rate averaged 11.1% during the first three IUI cycles. Pregnancy rates were > or = 8.2% per cycle when the initial sperm values were a concentration of > or = 5 X 10(6)/mL, a total count of > or = 10 X 10(6), progressive motility of > or = 30%, or a total motile sperm count of > or = 5 x 10(6). Minimal increases in fecundity occurred when initial values were greater than these threshold levels. The lowest initial values that resulted in pregnancy were a concentration of 2 x 10(6)/mL, a total count of 5 x 10(6). motility of 17%, and a total motile sperm count of 1.6 X 10(6). Pregnancy rates were <3.6% when initial values were between the threshold levels and the lowest levels. CONCLUSION(S): The sperm quality that is necessary for successful IUI is lower than World Health Organization threshold values for normal sperm. Intrauterine insemination is effective therapy for male factor infertility when initial sperm motility is > or = 30% and the total motile sperm count is > or = 5 X 10(6). When initial values are lower, IUI has little chance of success.

Adult↗

Relationship between varicocele size and response to varicocelectomy.

We studied the relationship between varicocele size and response to surgery in 86 men with a unilateral left varicocele who reported either infertility (83), pain (1) or pain and testicular atrophy (2). Varicoceles were graded according to size: grade 1--small (22 patients), grade 2--medium (44) and grade 3--large (20). Sperm count, per cent motility, per cent tapered forms and fertility index (sperm count times per cent motility) were measured preoperatively and postoperatively. Preoperatively, men with grade 3 varicocele had lower sperm counts and poorer fertility indexes compared to men with grades 1 and 2 varicocele. Sperm concentration improved significantly in men with grade 2 (33 +/- 5 million per cc preoperatively to 41 +/- 6 million postoperatively, p < 0.04) and grade 3 (18 +/- 5 million preoperatively to 32 +/- 7 million postoperatively) varicocele after microsurgical ligation of the varicocele. Motility improved significantly in men with grade 3 varicocele. Decrease in per cent tapered forms was significant in all groups. A comparison of per cent change in fertility index among the groups revealed that men with grade 3 varicocele improved to a greater degree (128%) than men with grade 1 (27%) or grade 2 (21%) varicocele. Pregnancy rates 2 years postoperatively were 40% for grade 1, 46% for grade 2 and 37% for grade 3 varicocele patients. The difference in pregnancy rates among the groups was not statistically significant. In conclusion, infertile men with a large varicocele have poorer preoperative semen quality but repair of the large varicocele in those men results in greater improvement than repair of a small or medium sized varicocele.

Adult↗

Transient testicular warming enhances the suppressive effect of testosterone on spermatogenesis in adult cynomolgus monkeys (Macaca fascicularis).

CONTEXT: The context of the study was to examine whether combined testosterone (T) and heat (H) treatment have additive or synergistic effects on suppression of spermatogenesis. OBJECTIVE: The objective of the study was to determine whether T+H induces a greater suppression of spermatogenesis than either treatment alone in monkeys. DESIGN: The study was a randomized, placebo-controlled study. SETTING: The study was conducted at a primate center in China. PARTICIPANTS: The study population was comprised of 32 adult cynomolgus monkeys. INTERVENTIONS: Groups of eight adult monkeys were treated for 12 wk with: 1) two empty implants (C); 2) two T implants (T); 3) daily testicular heat exposure (43 C for 30 min) for 2 consecutive days (H); or 4) two T implants plus testicular heat exposure (T+H). Treatment was followed by an 8-wk recovery period. MAIN OUTCOME MEASURES: Measures included sperm counts and germ cell apoptosis. RESULTS: Serum T levels were elevated in both the T and T+H groups during treatment but not in the C or H group. Sperm counts were transiently suppressed after heat to 16.4% of baseline at 4 wk and then returned to pretreatment levels. Sperm counts were suppressed slowly after T treatment to nadir of 6.4% of pretreatment levels at 12 wk. T+H rapidly suppressed sperm output as early as 4 wk to 3.9% of pretreatment levels that was maintained throughout treatment. The decreased sperm counts were due to increased germ cell apoptosis in all treatment groups. Sperm counts recovered to the pretreatment levels in all groups by 8 wk after treatment. CONCLUSION: This proof-of-concept study demonstrates that transient testicular warming enhances and hastens the effect of T implant on the suppression of spermatogenesis in monkeys.

Animals↗

The association of age and semen quality in healthy men.

BACKGROUND: Although the effect of maternal age on fertility is well known, it is unclear whether paternal age also affects fertility. This cross-sectional study sought to characterize the association between age and semen quality, a well-known proxy of fertility status. METHODS: A convenience sample of 97 non-smoking men (aged 22-80 years) without known fertility problems was recruited from a national government laboratory. The men provided semen samples and information relating to lifestyle, diet, medical and occupational details. Semen volume (ml), sperm concentration (x10(6)/ml), total sperm count (x10(6)), motility (%), progressive motility (%) and total progressively motile sperm count (x10(6)) were measured. RESULTS: After adjusting for covariates, semen volume decreased by 0.03 ml per year of age (95% CI: -0.05, -0.01); motility decreased by 0.7% per year (95% CI: -0.92, -0.43); progressive motility decreased by 3.1% per year (95% CI: -4.5, -1.6); and total progressively motile sperm count decreased by 4.7% per year (95% CI: -7.2, -2.2). There was a suggested decrease in sperm concentration and count. The proportion of men with abnormal volume, concentration and motility was significantly increased across the age decades. CONCLUSIONS: In a convenience sample of healthy men from a non-clinical setting, semen volume and sperm motility decreased continuously between 22-80 years of age, with no evidence of a threshold.

Adult↗

Paternal hyperphenylalaninemia.

In an article published in 1981 that reported on semen studies in four men with phenylketonuria (PKU), it was concluded that semen volumes were significantly reduced. However, the index case should not have been included in the statistical analyses. In the other three cases, the men with PKU had smaller semen volumes than did the four control medical students. The significance of these data depends upon the subjects' reliability in accurately reporting abstinence from ejaculation during the preceding four days. Significant differences were not found in sperm count per milliliter, total sperm count, motility, viability, and abnormal forms of sperm. The 1981 article has aroused concerns about both the ability of men with PKU to father offspring and the outcome for children who are conceived. In the present article, the author reports on one case of paternal benign hyperphenylalaninemia from her clinic and eight cases of presumably classical PKU that were previously reported. The nine cases include a total offspring of 33. Of these 33, eight had PKU, two had milder to moderate hyperphenylalaninemia, and one undiagnosed retarded child died at the age of 8 years. The 22 other offspring seem to be normal or similar to their non-PKU mothers. Three of the fathers had no hyperphenylalaninemic offspring. Two PKU offspring were from a mating of two PKU parents. Hyperphenylalaninemic men can obviously father children, but abnormalities other than hyperphenylalaninemia have not been seen.

Adult↗

Testicular abnormalities in male rats after lactational exposure to nonylphenols.

Lactational exposure of male rat pups to nonylphenols (NPs) decreased the size of their testes and male accessory glands. At 31 d of age, NP-treatment of male rats resulted in less cellular differentiation of the seminiferous tubules (STs) and increased intertubular space compared to controls. At maturity, NP-treated males showed varying degrees of abnormalities in the affected testes. In the moderately affected ones, about 20-30% of their STs had poorly differentiated germinal elements. Cell lineage was less organized. In extreme cases, all STs of the affected testis failed to differentiate into germinal elements. These abnormalities in germinal element differentiation might be the primary cause for a number of the NP-treated males having a lower epididymal sperm count and a lower percentage of motile sperm compared to age-matched control males. Zymogram analysis of testis homogenates by sodium dodecyl sulfate gelatin gels revealed two major forms (64-66 kDa and 50-52 kDa) of gelatinases. Only the 50-52-kDa form was greatly reduced or absent in the affected testis. Lactational exposure of male pups to NPs thus leads to various testicular abnormalities including lack of differentiation of STs, lowering of sperm count, and reduction in the percentage of motile sperm and modulation of a specific form of testicular proteinases.

Animals↗

A multicenter study evaluating the flowcytometric-based kit for semen analysis.

OBJECTIVE: To evaluate the precision and accuracy of a flowcytometric-based semen analysis kit and its application in four fertility centers, as compared with routine microscopic evaluation. DESIGN: A prospective comparative study. SETTING: Four fertility centers, located in Israel and the United States. PATIENT(S): Patients referred to fertility clinic for sperm evaluation. INTERVENTION(S): The precision of semen analysis by both methods was evaluated by inter- and intra-technician studies. The accuracy of the sperm counts obtained was assessed by counting a diluted sample and comparing the obtained results with the expected results according to the dilution factor. MAIN OUTCOME MEASURE(S): Sperm count, morphology, motility, viability, white cell count, antisperm antibodies. RESULT(S): The flowcytometric-based kit for semen analysis is more precise and accurate than the manual routine method. Smaller coefficient of variance (CV%) with results were obtained by the flowcytometric-based kit for all semen parameters as compared with the routine manual methods. Sperm density values determined by the flowcytometric-based kit correlated better with the dilution factor. The agreement rates between the flowcytometric and manual methods are sperm count 90%, motility 82%, vitality 70%, round cell counts 78%, and sperm bound antibodies 100%. CONCLUSION(S): Semen analysis by flowcytometric-based kit is advantageous because of improved precision and accuracy compared with the routine method. It provides similar clinical information to that obtained by routine method for sperm count, motility, and antisperm antibodies, and more accurate results for round cell counts (labeled all subclasses) and vitality.

Flow Cytometry↗

A fifteen-year study of alterations in semen quality occurring after vasectomy reversal.

Semen quality was evaluated in 256 men at 2, 4, 6, and 12 months after vasectomy reversal. Total sperm counts were normal and averaged 91 X 10(6) sperm per ejaculate. The percentage of live sperm was decreased below normal to 36% and hypo-osmolarity values indicated only 41% of the sperm with normal membranes. Progressive motility and the total progressively motile sperm count were reduced and averaged 25% and 27 million, respectively. Approximately 50% of the patients had positive titers of sperm agglutinating and/or sperm immobilizing antibodies. Sperm morphology indicated tail and head shape defects with increases in both tapered and immature sperm. A fertility score combining several sperm parameters averaged only 37% of normal. All of these values remained constant with time after reversal except for progressive motility (increased), oval head shapes (increased), and tapered sperm (decreased). This study has demonstrated that characteristic defects occur in sperm (decreased). This study has demonstrated that characteristic defects occur in sperm motility, sperm membrane function and morphology, in addition to specimen fertility scores, after a vasectomy reversal and need to be taken into consideration when advising and treating these patients for subsequent fertility difficulties.

Cell Survival↗

Evaluation of trend in semen analysis for 11 years in subjects attending a fertility clinic in India.

AIM: The data on semen analysis of subjects attending the Fertility Clinic at NIHFW (National Institute of Health and Family Welfare) Munirka, New Delhi for the last 11 years were analyzed to verify the claims and speculations on declining sperm counts in men. METHODS: Approximately 10 % of the records every year starting from 1990 to 2000 (numbering 1176 in total) were randomly selected for analysis. Subjects with azoospermia or severe oligozoospermia were excluded from analysis. RESULTS: The average age of the men attending the infertility clinic was 31.2 years. The average semen volume and sperm count were found to be (2.6+/-0.1) mL and (60.6+/-0.9)X10(6)/mL, respectively. No significant decline in sperm counts was observed in any year during the entire study period. Only 1.8 % of the total number of sperm counts in the random sampling were less then 20 X10(6)/mL. On the basis of WHO criteria on motility, the total percentage of non-progressive and non-motile sperm in the ejaculate was higher (63 %) as compared to the combined categories of slow and rapid linear progressive. CONCLUSION: The present study has confirmed similar findings from other different countries that declining sperm counts in humans is not a global phenomenon.

Adult↗

Semen quality of men employed at a lead smelter.

OBJECTIVE: To evaluate the effects of recent and long term occupational lead exposure on indicators of male reproductive health. METHODS: In a cross sectional study of male employees of a lead smelter (n = 2469), blood samples were obtained from 152 workers including 119 who also provided semen samples. Semen analysis and serum concentrations of testosterone, follicle stimulating hormone, and luteinising hormone were used as indicators of reproductive health. Semen and hormone variables were examined in relation to measures of current and long term body lead burden estimated from current blood lead concentrations and historical blood lead monitoring data. RESULTS: For current blood lead concentration groups of < 15, 15-24, 25-39, > 40 micrograms/dl, the geometric mean sperm concentrations were, respectively, 79.1, 56.5, 62.7, and 44.4 million cells/ml and geometric mean total sperm counts were 186, 153, 137, and 89 million cells (P for trend 0.04). Compared with workers with blood lead concentrations less than 15 micrograms/dl, workers with current blood lead concentrations of 40 micrograms/dl or more had an increased risk of below normal sperm concentration (odds ratio (OR) 8.2, 95% confidence interval (95% CI) 1.2-57.9) and total sperm count (OR 2.6, 95% CI 0.4-15.7), based on World Health Organisation standards. Independent of current lead exposure, sperm concentration, total sperm count, and total motile sperm count were inversely related to measures of long term lead exposure. No association was found between lead exposure and measures of sperm motility, sperm morphology, or serum concentrations of reproductive hormones. CONCLUSIONS: Blood lead concentrations below the currently accepted worker protection criteria seem to adversely affect spermatogenesis.

Adult↗

Sertoli cell number in testes of azoospermic men: trends in biopsy specimens.

The general male population has shown a long-term decline in sperm count. Induced hormonal imbalance can produce adverse reproductive effects in men, especially decreases in sperm count. One suggested cause for a decreased sperm count is a reduction in the number of Sertoli cells. The authors assessed numbers of Sertoli cells in testicular biopsy specimens obtained from azoospermic men between 1989 and 1999. The number of Sertoli cells per tubular area or circumference did not vary by year of biopsy among the tissue samples during this 10-year period. Patient age, taken as a measure of exposure duration to hypothesized abnormal hormonal environment, did not affect the number of Sertoli cells. Since no reduction in the number of Sertoli cells was observed, other pathogenic factors may be the cause of long-term decreases in sperm count.

Adult↗

[Clinical experience with methylcobalamin (CH3-B12) for male infertility].

CH3-B12 was administered daily (1,500 micrograms/day, for 4 to 24 weeks) to 26 infertile male patients who visited our clinic from January to December, 1982. It was not administered, however, to patients with azoospermia. Semen analysis was conducted from 8 weeks after the administration of CH3-B12. Sperm concentration increased in 10 cases (38.4%), total sperm counts increased in 14 cases (53.8%), sperm motility increased in 13 cases (50.0%) and total motile sperm count increased in 13 cases (50.0%). Semen volume, however, could not be evaluated due to wide variation. Serum LH, FSH and testosterone were unchanged. Judging by our criteria, 11 cases (42.3%) improved, 11 cases (42.3%) were unchanged and the remaining 4 cases (15.4%) had aggravated.

Adult↗

Changes in semen quality in Jerusalem between 1990 and 2000: a cross-sectional and longitudinal study.

The aim of the present study was to investigate whether sperm quality has changed during the years 1990-1999 among men residing in Jerusalem, Israel, who were involved in treatment by intrauterine insemination (IUI). Both cross-sectional and longitudinal analyses were performed. A total of 2638 male partners in couples that underwent treatment by IUI participated in the cross-sectional investigation. Of them, 417 men (16%) were included in the longitudinal study. Total sperm counts and percent motility were evaluated on an annual basis to assess changes over 10 years from 1990 through 1999. A significant downward trend in sperm count and motility was demonstrated in the cross-sectional study. Sperm count decreased by 5.2 x 10(6)+/-0.9 x 10(6) (p<.0001) each year and percent motility declined by 0.50+/-0.14% (p=.0003). Similar changes were found in the longitudinal evaluation, but they were not statistically significant. These data suggest that during the last decade in Jerusalem, sperm count and motility declined significantly among men involved in infertile relationships and treated by IUI.

Cross-Sectional Studies↗

The influence of semen analysis parameters on the fertility potential of infertile couples.

The objective of this study was to investigate the relationship between couples' fertility potential and several parameters of semen analysis (from a single semen sample/male partner) in a cohort of 1,055 infertile couples seen at the Texas Institute for Reproductive Medicine and Endocrinology for a total of 9,409 follow-up months. The medians of sperm concentrations (SC), total sperm counts (TSC), percent motility (MOT), motile sperm concentrations (MSC), and total motile sperm counts (TMSC) were significantly higher (P < 0.0001) in the group that achieved pregnancy. When the entire group was divided into "high" and "low" groups on the basis of the various parameters of semen analysis, the relative risk ratios for conception for the "high" groups were as follows: SC, 1.5; MOT, 8.5; TSC, 8.1; MSC, 5.8; and TMSC, 6.1. Life table analysis showed a statistically significant difference (P < 0.0001) in the initial rise and overall slope of the conception rates between the two groups for a number of the semen analysis parameters (TSC, MOT, MSC, and TMSC). This study showed that certain semen analysis parameters are positively correlated, with a high degree of statistical probability, with the time required for the occurrence of conception. The quantitative impact of the male fertility potential on conception rates was shown to correlate not solely with the SC or MOT values, but even more so with their derivatives (i.e., MSC and TMSC). Therefore, in an in vivo environment it is not only the number of sperm and their motility but also their derivatives that provide a quantitative insight into the male fertility potential. The data may provide a quantitative expression of the relative risk ratio for conception to occur and the time required until conception is achieved. Further studies will be necessary to clarify the effect of the other semen analysis parameters (i.e., morphology, velocity, linearity, and "efficient" MSC) on conception rates, cumulative conception rates, relative risk ratio for conception, and time until conception in a large population of infertile couples.

Age Distribution↗