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Effect of ethylene glycol monomethyl ether on spermatogenesis, dominant lethality, and F1 abnormalities in the rat and the mouse after treatment of F0 males.

Adult male CD rats and CD-1 mice were given a single oral dose of ethylene glycol monomethyl ether (EGM) at 0, 500, 750, 1,000, or 1500 mg/kg. Groups of 10 were killed at weekly intervals after dosing for analysis of sperm counts and morphology or testicular histology; further groups of 10 were sequentially mated to pairs of virgin females to test for dominant lethality or gross foetal malformations in the F1 generation (F1 abnormalities). EGM was found to deplete the spermatocytes of both species severely, principally pachytene cells, but with other stages affected with increasing dose. A delay in the progression of spermatogenesis may account for a discrepancy between the apparent stage-specificity of damage deduced from lowered sperm counts and that observed histologically. In the rat, morphological abnormalities were observed in sperm that had been exposed as spermatocytes; in the mouse, however, the sensitive cells were the late spermatocytes and early spermatids. In all these parameters there was an indication of a dose-response relationship in both rats and mice. In the mating studies EGM induced a dose-related decrease in fertility 5 weeks after dosing in the rat, but complete sterility in all but the lowest dose after 6 weeks. In contrast, EGM had no effect on the reproductive capacity of the mouse. There was no statistically significant evidence for the induction of dominant lethal mutations or F1 abnormalities in either species. A single oral dose of cyclophosphamide (CTX) at 100 mg/kg induced a significant increase in dominant lethality in both species. CTX reduced the number of total implants in the rat and induced a nonsignificant increase in the number of abnormal offspring sired by treated male mice.

Abnormalities, Drug-Induced↗

Electroejaculation in spinal cord injured males.

Electroejaculation is a newly developed method to retrieve sperm in anejaculatory spinal cord injured (SCI) males. We studied 25 completely traumatic SCI males from August 1990 to May 1991. The patients' ages ranged from 18.7 to 43.3 years, and the interval since injury ranged from four months to 14.1 years. The level of injury varied from C5 to T12. Bi-directional emission was found in 12 patients, antegrade in nine, retrograde in one and failure in three. Electroejaculatory stimulation parameters were 434 +/- 54 mA for mean maximum current, 21.7 +/- 2.7 volts for mean maximum voltage and 35.9 +/- 3.1 degrees C for mean maximum probe temperature. The antegrade semen obtained showed wide variations in sperm quality and quantity between subjects. The total sperm count was 478 +/- 809 x 10(6) in the antegrade portion, and the sperm motility was below 5% in most cases. The retrograde portion was usually worse. There was no correlation between sperm quality and quantity with patient age, injury level or injury period. Bladder management had no effect on the results of electrical stimulation. Epididymitis had a negative impact on the success of retrieval. Low-level injury victims needed analgesia or anesthesia to complete the stimulation. The major side effects were minimal autonomic dysreflexia and mild rectal mucosal change. Repeated stimulation may improve sperm counts, but semen quality deteriorates if the procedure is performed once a week. As a whole, electroejaculation is a safe, effective and simple procedure to retrieve sperm in anejaculatory persons, especially SCI patients.

Adolescent↗

Can LDH activity in spermatic vein indicate testicular damage? A preliminary report.

We aimed to investigate the relationship between varicocele and lactic dehydrogenase (LDH), an intracellular enzyme that indicates cellular damage. LDH levels were measured in the blood samples of 17 oligoasthenospermic infertile patients with varicocele which were obtained synchronously from spermatic and peripheral veins during operation. Sperm counts ranged from 1 to 74 million/ml, while motility ranged from 10% to 60%. LDH level in spermatic vein was found statistically higher than the level in peripheral vein (p = 0.042). There was no correlation between sperm counts and LDH level in spermatic vein. We found a significant increase in spermatic vein LDH level in varicocele. We think that further studies are needed to reveal the relationship between spermatic vein LDH level and varicocele.

Adult↗

The interpretation and significance of the fractional postcoital test.

The investigation was designed to objectively determine the clinical usefulness of the fractional postcoital test. Forty-three normal subjects had midcycle cervical mucus collection at various times after insemination. There was a significant correlation between the number of motile sperm at the internal os level and the total sperm count within the cervical mucus. The median internal os count was 15 motile sperm per high-power field with a lower 95% confidence limit of five motile sperm per high-power field. Therefore, the fractional postcoital test is useful clinically as it is a physiologic indication of sperm transport in cervical mucus.

Adult↗

Evaluation of T-lymphocyte subsets present in semen and peripheral blood of healthy donors: a report from the heterosexual transmission study.

The purpose of this study was to accurately determine the T-lymphocyte subsets found in semen from healthy volunteers, to evaluate the impact of repeated ejaculation on the frequency or type of immune cells present in semen, and to compare subset analysis in semen to that in the peripheral blood. To accomplish this, a flow cytometric method was developed to identify and count immunophenotypically distinct cells present in semen. Fresh semen samples and peripheral blood were collected over three consecutive days from nine healthy donors. Donors had normal ejaculate volume, sperm count, sperm motility, morphology, and leukocyte count. No significant intra-donor differences were seen in these parameters over time. No significant differences were observed in the percentage of CD3+ cells, CD4+ cells, CD8+ cells, and the CD4:CD8 ratio in semen on consecutive days. However, within the CD4+ subset, when naive and memory CD4+ cells were measured, some day to day variability was suggested. No significant differences in CD3+, CD4+, CD8+, CD4/CD8 ratio, or naive and memory subsets were seen in the peripheral blood between sampling days. When semen was compared to peripheral blood some differences in immune subset values were observed, with an increase in the percentage of memory CD4+ cells in semen being the most striking. This finding may be relevant to HIV transmission, since others have shown that this cell may be preferentially infected with HIV and is the primary reservoir for virus in infected individuals.

Adult↗

Leukocytospermia in male infertility patients in China.

Recent studies have revealed a high prevalence of leukocytospermia (> 1 x 10(6) white blood cells ml-1 semen) in male infertility patients in the USA and certain European countries, and have implicated white blood cells as a cause of infertility. Since leukocytospermia may often be attributed to male genital-tract infections, its prevalence could vary widely in different populations depending on factors such as sexual practices and the prevalence of sexually transmitted pathogens. In the study described here the incidence of leukocytospermia was determined in a group of 101 male infertility patients and a small reference group of normal fertile men in Beijing, China. Seminal white blood cells (WBC) and WBC sub-populations were enumerated by peroxidase staining and immunohistological assay. Eight out of 101 (7.9%) samples from infertility patients and 0/10 samples from fertile donors were leukocytospermic. The incidence of leukocytospermia in the Chinese infertility patients was considerably lower than the 23% incidence observed in a recent study of infertility patients in the USA using a similar technique. All but one of the patients with leukocytospermia had a poor sperm count and/or poor sperm motility. However, due to the low incidence of leukocytospermia and the small number of patients in this group, a statistically significant association between leukocytospermia and poor semen quality was not attained. The simple peroxidase test correlated well with the more expensive and technically demanding immunohistological assay for detection of white blood cells in semen.

Adult↗

Radiation protection of male fertility in mouse and rat by a combination of 5-hydroxy-L-tryptophan and a thiol compound (AET).

Sperm abnormalities and fall in total sperm count following different doses (4 Gy, 5 Gy and 6 Gy) of whole body gamma irradiation (WBGR) were studied in adult male Swiss strain A mice. The protecting ability of a combination of 5-hydroxy-L-tryptophan (5-HTP, 100 mg/kg) and 2-aminoethyl isothiuronium bromide hydrobromide (AET, 20 mg/kg) was also investigated. Pretreatment with a 5-HTP+AET formulation i.p., 30 min before irradiation modified the fall in sperm counts significantly. Exposures to 4 Gy, 5 Gy and 6 Gy WBGR caused marked increase of sperm abnormalities which could be significantly reduced by pretreatment with 5-HTP-AET. WBGR with 4 Gy, 5 Gy and 6 Gy produced a short period of sterility associated with oligospermia but these abnormalities were corrected by pretreatment with 5-HTP+AET. This finding was supported by breeding experiments in pretreated adult male Sprague-Dawley rats which showed delivery of normal offsprings in drug-protected irradiated groups in contrast to irradiated controls.

5-Hydroxytryptophan↗

Hormonal contraception in Chinese men: variations in suppression of spermatogenesis with injectable testosterone undecanoate and levonorgestrel implants.

AIM: To explore the causes of the difference in spermatogenic suppression between responders and non-responders in Chinese men treated with levonorgestrel (LNG) implants plus testosterone undecanoate (TU) injectable. METHODS: The 16 Chinese volunteers treated were divided into two groups in regard to the sperm count during the treatment period, 7 men in the responder group (Group R), including 6 azoospermia and one severe oligozoospermia, and the remaining 9 in the non-responder group (Group N), including 4 oligozoospermia and 5 with sperm counts greater than 20 x 10(6)/mL. The differences in serum profiles of FSH, LH, T, LNG and T/LH ratio were compared between the two groups and the correlation between the seminal fluid parameters and serum reproductive hormones was analyzed. RESULTS: The serum FSH level was lower in Group R than that in Group N (P<0.05), while the serum LH and LNG levels were higher in Group R than those in Group N (P<0.05). The sperm density (P<0.01, r=0.235), motility(P<0.01, r=0.326) and vitality (P<0.01, r=0.219) showed significantly positive correlation with the serum FSH level. CONCLUSION: The blood LNG and T levels, the degree of FSH inhibition and/or the sensitivity of the pituitary-testis axis to exogenous steroids, as well as the individual spermatogenetic potential and the functional status of the Leydig cells may be factors bringing about individual differences in spermatogenic suppression in Chinese men treated with LNG and TU.

Adult↗

Evidence for decreasing quality of semen during past 50 years.

OBJECTIVE: To investigate whether semen quality has changed during the past 50 years. DESIGN: Review of publications on semen quality in men without a history of infertility selected by means of Cumulated Index Medicus and Current List (1930-1965) and MEDLINE Silver Platter database (1966-August 1991). SUBJECTS: 14,947 men included in a total of 61 papers published between 1938 and 1991. MAIN OUTCOME MEASURES: Mean sperm density and mean seminal volume. RESULTS: Linear regression of data weighted by number of men in each study showed a significant decrease in mean sperm count from 113 x 10(6)/ml in 1940 to 66 x 10(6)/ml in 1990 (p < 0.0001) and in seminal volume from 3.40 ml to 2.75 ml (p = 0.027), indicating an even more pronounced decrease in sperm production than expressed by the decline in sperm density. CONCLUSIONS: There has been a genuine decline in semen quality over the past 50 years. As male fertility is to some extent correlated with sperm count the results may reflect an overall reduction in male fertility. The biological significance of these changes is emphasised by a concomitant increase in the incidence of genitourinary abnormalities such as testicular cancer and possibly also cryptorchidism and hypospadias, suggesting a growing impact of factors with serious effects on male gonadal function.

Humans↗

Some observations on human semen analysis.

Semen analysis of 66 unmarried medical students in the age group of 17-21 years was carried out. A higher liquefaction time pH, motility, lower sperm count and abnormal forms were observed compared to reported values. Liquefaction time, pH and sperm count was found significantly different in non-vegetarians and vegetarians, perhaps due to difference in their dietary proteins.

Adolescent↗

Semen quality among Danish and Finnish men attempting to conceive. The Danish First Pregnancy Planner Study Team.

OBJECTIVE: To assess differences in semen quality between similar populations from Denmark and Finland. DESIGN: Comparison of semen quality between 221 Finnish men (of whom 115 had no proven fertility) and 411 Danish men with no proven fertility in two follow-up studies among normal couples trying to conceive. METHODS: In Finland male partners of couples without experienced infertility attempting to conceive were recruited through advertisements in local newspapers from 1984 to 1986. From 1992 to 1995 Danish men who lived with a partner and who had not attempted to achieve a pregnancy previously were recruited through their union when they discontinued birth control. All semen analyses were performed in accordance with the World Health Organization guidelines. RESULTS: Median sperm concentration, total sperm count and the percentage of morphologically normal spermatozoa were significantly higher among the Finnish men without proven fertility (104.0 million/ml, 304.0 million and 58% respectively) compared with the Danish men (53.0 million/ml, 140.8 million, and 41% respectively). Sperm concentration was 105.7% (95% confidence interval (CI) 58.1%-167.6%) and total sperm count was 127.4% (95% CI 71.4%-201.6%) higher among Finnish men without proven fertility than among Danish men after control for confounders. CONCLUSIONS: Some, but hardly all, of the observed difference in semen quality may be explained by differences in recruitment procedures, selection of the men and by methodological differences in semen analysis between the two countries. Also a birth cohort effect may explain some of the differences between countries as the Finnish men were recruited 11 years before the Danish men. Therefore, follow-up studies with identical recruitment and selection of men from the two countries are needed.

Adult↗

Fertility patterns prior to testicular cancer diagnosis.

Although prenatal factors are associated with testicular cancer etiology, few studies have examined the reproductive profiles of men prior to diagnosis. This case--control study investigated fertility patterns prior to testicular cancer diagnosis by comparing pregnancies fathered by 201 men with testicular cancer and those fathered by 204 age- and neighborhood-matched controls. Regardless of histology, men with testicular cancer were less likely to have ever fathered a live-born infant (OR 0.67, 95% CI 0.42--1.06) and had fewer offspring than control men (means 1.8 and 2.1, respectively). Cases were more likely than controls to report having an infertility diagnosis (OR 9.47, 95% CI 1.19--75.2) or a low sperm count (OR 5.85, 95% CI 1.28--26.7) prior to cancer diagnosis. No differences were observed for pregnancy loss. These results indicate that men with testicular cancer may have impaired fecundity and fertility as evidenced by an infertility diagnosis or low sperm count and fewer live births. Further research is needed to determine the extent to which reproductive factors are involved in the etiology of testicular cancer.

Adult↗

Antifertility effects of Ricinus communis (Linn) on rats.

The antifertility effects of 50% ethanol extracts of Ricinus communis have been studied in male rats. There was a drastic reduction in the epididymal sperm counts. Alteration in the motility, mode of movement and morphology of the sperms were observed. Reductions in the fructose and testosterone levels were suggestive of reduced reproductive performance. Reversibility tests showed that the antifertility effect of Ricinus communis was completely reversible on withdrawal of the drug. The ethanol extracts of Ricinus communis did not cause any hepatotoxicity since the hepatic GOT and GPT levels were unaltered.

Acid Phosphatase↗

Effect of different types of textile fabric on spermatogenesis: an experimental study.

The effect of different types of textile fabric on spermatogenesis was studied. Twenty-four dogs were divided into two equal groups, one of which wore cotton underpants and the other polyester ones. Seven dogs wearing nothing were used as controls. The underwear was fashioned to fit loosely in the scrotal area so as to avoid its insulating effect. It was worn continuously for 24 months during which the semen character, testicular temperature, hormones (serum testosterone, follicle stimulating hormone, luteinizing hormone, prolactin) and testicular biopsy were examined. The garment was then removed, and the same investigations repeated through another 12 months. The results were analysed statistically. In the polyester group the testicular temperature showed insignificant changes during the period when the pants were worn (P > 0.05). By the end of the 24 months there was a significant decrease in sperm count and motile sperms, with an increase in abnormal forms (P < 0.001); the testicular biopsy showed degenerative changes. After garment removal the semen character improved gradually to normal in 10 dogs; two remained oligozoospermic. There were insignificant changes (P > 0.05) in hormones during the study. In contrast, the cotton and control groups showed insignificant changes (P > 0.05) in all the aforementioned parameters during the 36 months of the study. The polyester pants thus had a deleterious effect on spermatogenesis in the dogs which was, however, reversible in the majority of cases. The cause of this effect is unknown, but it may be assumed that the electrostatic potentials generated by the polyester fabric play a role in it.

Animals↗

The effects of temperature on the activity of testicular steroidogenic enzymes.

Decreased sperm counts and impaired sperm motility are present in a substantial proportion of men with varicocele. Elevations in the temperature of the affected testis, and increased spermatic vein estradiol (E2) concentrations have been found in some of these patients. To investigate the possibility that increases in temperature lead to a pattern of testicular steroidogenesis that results in increased E2 synthesis, we have examined the effects of temperature changes on the activities of four important testicular steroidogenic enzymes. 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 17-hydroxylase (17-OH), 17,20-desmolase (17,20-D) and aromatase activities were measured in the microsomal fraction of rat, pig and horse testes. Incubations were performed at 34 degrees C, 36 degrees C, and 38 degrees C. The activities of all 4 enzymes increased with each 2 degrees C temperature elevation in roughly proportional amounts. We conclude that minor elevations in incubation temperature are associated with increases in the in vitro activity of four key testicular steroidogenic enzymes.

Aldehyde-Lyases↗

Genetic monitoring of aluminum workers exposed to coal tar pitch volatiles.

A group of 50 workers exposed to coal tar pitch volatiles (CTPV) in an aluminum reduction plant and a group of 50 non-exposed workers were selected to evaluate the genotoxic effects of CTPV exposure. A battery of tests was performed on 3 different body fluids; urine, blood and semen. Urine samples were evaluated for mutagenic constituents using the Ames/Salmonella assay. Cultured lymphocytes from blood samples were used to perform cytogenetic analysis. Semen samples were used to measure sperm count, percent abnormal sperm morphology and frequency of sperm carrying double fluorescent bodies (2-F). 14 of 28 (50%) exposed workers and 7 of 36 (19.4%) non-exposed workers had mutagenic urine. This difference was significant (p less than 0.01). Among the non-smokers a significantly higher percentage of workers who were exposed had positive urine (36%) compared to the non-exposed workers (5%) (p less than 0.05). Among the exposed group, more mechanics had mutagenic urine than did other types of workers. Overall chromosome aberration rates were similar in both exposed and non-exposed workers. Among exposed workers a significant inverse correlation (p less than 0.05) between age and chromatid aberration rate was observed. Results of semen analysis failed to detect differences between exposed and non-exposed workers. Results of these tests lend support to a battery approach to genetic monitoring and suggest a link between exposure to CTPV and genotoxic effects. Detection of exposure to mutagens at an early time offers an opportunity for disease prevention by the reduction of exposure.

Adult↗

An assessment of the potential developmental and reproductive toxicity of di-isoheptyl phthalate in rodents.

Di-isoheptyl phthalate (DIHP) is a branched, phthalate ester with seven carbon alkyl side chains. Since structurally similar phthalates have been shown to produce developmental and/or reproductive effects in rodents, the potential for DIHP to produce developmental and reproductive toxicity was assessed. In a developmental toxicity study, female rats were given DIHP by oral gavage on gestational days 6-20. There were significant reductions in uterine weight, increased resorptions and reduced fetal weight in the high dose (750 mg/kg) group. Fetal examination revealed malformations and variations of both the skeletal system and the viscera including ectopic testes. The intermediate dose, 300 mg/(kg/day), was a no effect level in this study. In a two-generation reproductive toxicity study, DIHP was given in the diet at 1000, 4500 and 8000 ppm. In the 8000 ppm group of the first (F1) generation, anogenital distance was reduced, time to balanopreputial separation was increased, there was a significant increase in thoracic nipples and testicular abnormalities, and weights of testes and accessory reproductive organs were significantly reduced. Testicular sperm counts and daily sperm production were significantly reduced. Fertility was also significantly reduced in the 8000 ppm group. In the second (F2) generation offspring, anogenital distance was significantly reduced and there was evidence of reduced weight gain during lactation in both the 4500 and 8000 ppm groups. The overall no effect level (NOEL) in the reproductive toxicity study was in the range of 64-168 mg/(kg/day) (gestation-lactation periods). By comparison, estimated average human exposures in the general population are <1 microg/(kg/day).

Animals↗

Developmental expression and function of Bmp4 in spermatogenesis and in maintaining epididymal integrity.

Bone morphogenetic proteins (BMPs) play essential roles in many aspects of developmental biology. We have previously shown that Bmp7, Bmp8a, and Bmp8b of the 60A class of Bmp genes have additive effects in spermatogenesis and in maintaining the epididymal integrity of the caput and caudal regions. Here we report that Bmp4 of the Dpp class has a unique expression pattern in the developing testis and epididymis. Bmp4 heterozygous males on a largely C57BL/6 background show compromised fertility due to degeneration of germ cells, reduced sperm counts, and decreased sperm motility. More interestingly, some of these males show extensive degeneration of the epididymal epithelium in the corpus region, rather than in the caput and cauda regions as for Bmp7 and Bmp8 mutants. Thus, these genetic data reveal a region-specific requirement of different classes of BMPs for epididymal epithelium to survive and have significant implications on male reproductive health and perhaps birth control.

Animals↗