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In vivo and in vitro evaluations of spermatotoxicity induced by 2-ethoxyethanol treatment.

2-Ethoxyethanol (EE), a member of the glycol ethers, has been shown to produce testicular atrophy in laboratory animals. The present study further identified the spectrum of effects on the male reproductive system in vivo and initiated in vitro studies on possible mechanisms of action. Adult, male rats were treated (po) with 0 or 936 mg EE/kg, 5 days/week for 6 weeks. Semen samples were collected on a weekly basis during the exposure period from ovariectomized, hormonally primed females immediately following mating and analyzed for sperm count, sperm morphology, and sperm motility. Sperm count and percent normal morphology were decreased at Weeks 5 and 6, and sperm motility was decreased at Week 6. These data, along with other studies, indicated that the pachytene spermatocyte was the most sensitive target for EE. In vitro studies monitored O2 consumption and ATP concentrations in isolated pachytene spermatocytes which were treated with 10 mM EE or 1 or 10 mM ethoxyacetic acid (EAA), the reported active metabolite of EE. An increase in respiratory ratio for the lactate rate/endogenous rate and a decrease in the 2,4-dinitrophenol rate/lactate rate were observed only for cells treated with 10 mM EAA. Additionally, a decrease in ATP concentration was seen only with 10 mM EAA. These results indicated that EAA interfered with energy metabolism in the pachytene spermatocyte. This effect may, in part, explain the testicular toxicity produced by this compound.

Acetates↗

Reproductive toxicity evaluation of vanadium in male mice.

The reproductive toxicity of vanadium was studied in mice. Male Swiss mice were exposed to sodium metavanadate at doses of 0, 20, 40, 60, and 80 mg/kg per day given in the drinking water for 64 days. To evaluate the fertility of the vanadium-treated animals, males were mated with untreated females for 4 days. A significant decrease in the pregnancy rate was observed at 60 and 80 mg/kg per day of sodium. metavanadate. However, metavanadate did not reduce fertility in male mice at 20 and 40 mg/kg per day. Reproductive toxicity was measured by sperm count, sperm motility, organ weights, and histologic evaluation of the testes. Decreased body and epididymis weight was only observed in the 80 mg/kg per day group, while testicular weights were not altered by the treatment with all doses used. Sperm count was significantly decreased at 40, 60, and 80 mg/kg per day, but the sperm motility was unaffected. Histopathological examination revealed that the testes were normal and that the epididymis of treated male mice contained normal appearing sperm. The no observed adverse effect level (NOAEL) was 40 mg/kg per day. Consequently, vanadium would not cause any adverse effect on fertility or testicular function in male mice at the concentrations usually ingested by humans through the diet and drinking water.

Animals↗

Significance of inflammation on standard semen analysis in chronic prostatitis/chronic pelvic pain syndrome.

The impact of defined urogenital inflammations on standard ejaculate parameters is still a matter of controversial debate. Basic spermiogram parameters has been analysed in patients with inflammatory and noninflammatory chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS-NIH IIIA/IIIB) with regard to indicators of inflammation in prostatic secretions and/or the ejaculate. A total of 112 consecutive patients symptomatic for chronic pelvic pain were included in the study. All of them underwent a 'four glass-test' including leukocyte determination in expressed prostatic secretions followed by ejaculate analysis according to WHO. The analysis included pH, volume, total sperm count, sperm density, motility, morphology (Shorr stain), vitality (eosin stain), and counting of peroxidase positive leukocytes (PPL). Patients were first subgrouped according to elevated leukocyte counts in prostatic secretions, and then according to the number of PPL in semen. Leukocytes neither in the prostatic secretions nor in the ejaculate were associated with reduced standard semen parameters. Our data supports previous results that elevated leukocyte counts in prostatic secretions and in ejaculate, as indicators of inflammation have no negative impact on total sperm count, sperm density, motility, morphology, and sperm vitality in patients with CP/CPPS.

Chronic Disease↗

[Resistant effect of water decoction of root of Crataegus cuneata on male infertility induced by GTW in rats].

OBJECTIVE: To observe the effects of water decoction of the root of Crataegus cuneata on infertility induced by multi-glucoside of Tripterygium wilfordii (GTW) in rats. METHOD: Male adult rats were randomly divided into five groups, which were treated via gastric gavage of distilled water (1 mL x kg(-1)) , solution of GTW (10 mg x kg(-1)) and three doses of water decoction of root of C. cuneata (1.8, 5.4, 18 g x kg(-1)) + GTW (10 mg x kg(-1)), respectively. 8 weeks later, GTW was stopped and the decoction and water continued for another 4 weeks. And then, all the male rats were copulated with adult female rats. The rates of pregnancy, average numbers of embryos and luteum of female rats, relative weights of reproductive organs, sperm counts, sperm motility and viability were compared among all the groups. The histology and ultrastructure of testis and epididymis were observed, while the concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testostorone (T) in serum and T in testicular homogenate were detected by radioimmunoassay. RESULT: Compared with those in GTW model group, the embryo numbers, the relative weight of testis and epididymis and sperm counts and motility in C. cuneata groups were increased obviously (P < 0.05). After treatment, the morphological damages of seminiferous tubules and sperms were recovered, while concentrations of T in testicular homogenate were also significantly increased (P < 0.01). CONCLUSION: C. cuneata could relieve the reproductive lesions induced by GTW, and hence improve the uberty of the male infertile model rats.

Animals↗

Dose-response studies on male reproductive parameters in dogs with nafarelin acetate, a potent LHRH agonist.

Adult male beagle dogs were administered daily subcutaneous injections of either 0.5 or 2.0 micrograms/kg of a potent LHRH agonist, nafarelin acetate, for 44 days. Although there was a rise in the circulating levels of the gonadotropins and of testosterone following the early injections of agonist, continued treatment caused a marked decline in acute response and basal levels of both LH and testosterone and smaller decreases in the acute FSH response. The decline in LH and testosterone was accompanied by decreases in testicular volume, ejaculated sperm count, sperm motility, ejaculate volume, and duration of ejaculation. The decline in these parameters was more rapid at 2.0 micrograms/kg than at 0.5 micrograms/kg. The profile of responses to 2.0 micrograms/kg could be superimposed on that previously shown for the injection of 10.0 micrograms/kg. At the end of treatment, prostate weights were 36% and 68% of vehicle-treated controls for high- and low-dose animals, respectively. Spermatogenesis was absent in the testes of all agonist-treated animals. Over the dose range tested, the dose-response on all parameters was characterized by a slower evolution to the same maximal effect, rather than by a partial effect. If these data can be extrapolated to man, they would suggest that administration of higher dose levels of LHRH agonists than presently reported should be explored.

Animals↗

Effects of subchronic ifosfamide-mesna treatment on testes and semen characteristics in the rabbit.

Ifosfamide, a chemotherapeutic agent with a broad spectrum of antineoplastic activity, is concurrently administered with the uroprotectant mesna to avoid the urotoxic effect. This study was undertaken to investigate possible effects of ifosfamide-mesna treatment on the testes and semen characteristics in rabbits. Sexually mature New Zealand White male rabbits received intravenously 10 weekly treatments of ifosfamide+mesna (groups A, B and C received 30, 45 or 60 mg/kg of body weight ifosfamide+6, 9 or 12 mg/kg of body weight mesna, respectively, followed by a second equal dose of mesna 4 h later); groups MA, MB and MC received mesna alone at corresponding doses; and group S received normal saline. Reproductive organ weight as well as various qualitative and quantitative parameters of testis histology (minor diameter of seminiferous tubules, the most advanced germ cell type in seminiferous tubule identified in cross sections, and the number of germ cells per stage 1 seminiferous tubule cross section) were determined 1 day and 20 weeks after the treatment period, while semen quality (sperm count, sperm morphology and sperm progressive motility) and libido were evaluated on a weekly basis. Changes were noted only in the ifosfamide+mesna treated animals. One day after treatment, reproductive organ weights were decreased in groups A-C. Major histopathological lesions were not found; however, quantitative histological endpoints were altered in groups A-C. Transient oligospermia and teratozoospermia were noted in groups B and C, while asthenozoospermia was observed in group C only. The time course of these sperm alterations suggested possible bioaccumulation and residual activity of ifosfamide. Libido remained normal. The decrease in reproductive organ weights persisted in groups B and C to 20 weeks after treatment but only one quantitative histological endpoint, the number of the round spermatids per stage 1 seminiferous tubule cross section, remained decreased in group C. These results suggest that subchronic treatment with ifosfamide-mesna suppressed spermatogenesis and epididymal sperm maturation in the rabbit. Germinal epithelium recovery was not complete because although sperm characteristics returned to pretreatment values, not all histological alterations were ameliorated.

Animals↗

Reproductive toxicity of chromium in adult bonnet monkeys (Macaca radiata Geoffrey). Reversible oxidative stress in the semen.

The present study was designed to test the hypothesis that oxidative stress mediates chromium-induced reproductive toxicity. Monthly semen samples were collected from adult monkeys (Macaca radiata), which were exposed to varying doses (50, 100, 200 and 400 ppm) of chromium (as potassium dichromate) for 6 months through drinking water. Chromium treatment decreased sperm count, sperm forward motility and the specific activities of antioxidant enzymes, superoxide dismutase and catalase, and the concentration of reduced glutathione in both seminal plasma and sperm in a dose- and duration-dependent manner. On the other hand, the quantum of hydrogen peroxide in the seminal plasma/sperm from monkeys exposed to chromium increased with increasing dose and duration of chromium exposure. All these changes were reversed after 6 months of chromium-free exposure period. Simultaneous supplementation of vitamin C (0.5 g/L; 1.0 g/L; 2.0 g/L) prevented the development of chromium-induced oxidative stress. Data support the hypothesis and show that chronic chromium exposure induces a reversible oxidative stress in the seminal plasma and sperm by creating an imbalance between reactive oxygen species and antioxidant system, leading to sperm death and reduced motility of live sperm.

Animals↗

Reduction of spermatogenesis and steroidogenesis in mice after fentin and fenbutatin administration.

The present study was designed to assess potential reproductive toxicity caused by fentin and fenbutatin in the mice. Adult male mice received i.p. injections of fentin hydroxide and fenbutatin oxide at a dose of 0, 10 or 25 microg/kg body weight on 1st, 3rd and 5th day of experimentation. Mice were sacrificed on day 25 and analyzed for spermatogenesis and steroidogenesis. A significant decrease in epididymal sperm count, sperm motility, sperm viability and sperm function (HOS coiling) were observed in experimental mice when compared with controls. The decrease in sperm quantity and quality was significant in the 25 microg/kg group than that in the control group. The activity levels of testicular steroidogenic enzymes, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17beta-hydroxysteroid dehydrogenase (17beta-HSD) were significantly decreased in treated mice indicating decreased steroidogenesis after organotin compounds administration. The levels of serum testosterone decreased with an increase in follicle stimulating hormone and luteinizing hormone in experimental mice when compared to control mice. The results suggest that fentin and fenbutatin cause impairment of spermatogenesis through the inhibition of testosterone production.

17-Hydroxysteroid Dehydrogenases↗

The prostaglandin inhibitor effect of antiinflammatory drugs in the therapy of male infertility.

The effects of various doses of indomethacin and ketoprofen as compared with placebo were examined in 100 oligospermic patients who participated in this study. It was found that the treatment increased sperm count, sperm motility, and fertilizing capacity. The radioimmunoassay examination showed an increase in plasma follicle-stimulating hormone and luteinizing hormone but a decrease in testosterone. The results show that the influence of indomethacin was better in the dose of 75 mg daily. The mechanism of those changes is not clear. Treatment should be at least 60 days.

Adult↗

Mycoplasmas and in vitro fertilization.

Semen samples taken from 135 patients attending an in vitro fertilization clinic were shown to be colonized, 53 with Ureaplasma urealyticum (39%) and 16 with Mycoplasma hominis (12%). An unidentified mycoplasma species was isolated from the sperm of two patients. M. hominis was recovered from all the washed sperm samples taken from colonized semen, whereas washing the sperm eradicated U. urealyticum from 71% of colonized semen. The presence of mycoplasmas in semen made no significant difference to the sperm count, sperm motility, sperm abnormalities, or fertilization of eggs.

Bacteriological Techniques↗

Semen quality of workers occupationally exposed to hydrocarbons.

OBJECTIVE: To determine whether occupational exposure of men to hydrocarbons has adverse effects on the quality of their semen. DESIGN: Comparative study. SETTING: The rubber industry in Mexico City. PATIENT(S): Forty-eight workers who were exposed to hydrocarbons for 2-24 years and 42 unexposed workers. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Environmental hydrocarbon concentrations were determined by continuous air monitoring in all areas of the factory. Analyses of semen samples were performed in accordance with World Health Organization criteria. RESULT(S): Hydrocarbon concentrations were as follows: ethylbenzene, 220.7-234 mg/m3; benzene, 31.9-47.8 mg/m3; toluene, 189.7-212.5 mg/m3; and xylene, 47-56.4 mg/m3. The number of subjects with ejaculates that had normal characteristics was greater in the unexposed group (76%) than in the exposed group (17%). More abnormal characteristics were found in the semen of exposed workers than unexposed workers, including alterations in viscosity, liquefaction capacity, sperm count, sperm motility, and the proportion of sperm with normal morphology. Some abnormal characteristics correlated with the number of years of exposure to the hydrocarbons. CONCLUSION(S): Damage to the spermatogenic process resulting from hydrocarbon exposure was demonstrated by an increased rate of abnormalities in the semen of exposed workers compared with unexposed workers. This information may be useful for conducting future analyses of reproductive risks related to exposure to high concentrations of hydrocarbons.

Adult↗

Sperm characteristics and accessory sex gland functions in HIV-infected men.

A comparative study was carried out in the andrology clinic, Parirenyatwa Hospital, Harare, Zimbabwe, to investigate the sperm characteristics and accessory sex gland functions in HIV-infected individuals. Sixty-two patients with infertility problems who attended the clinic were requested to donate semen and blood after consent was obtained. HIV antibodies in paired semen and blood samples, sperm morphology, sperm count, sperm motility, seminal leucocytes, seminal fructose, seminal neutral alpha-glucosidase, and citric acid were analyzed. Nine out of 31 blood samples tested positive, while 21 out of 62 semen samples were positive for HIV. Leucocytospermia was associated with HIV-seropositive men (p < .01). The accessory sex gland function, as evaluated by biochemical markers, was not affected in HIV-seropositive men. HIV causes impairment of sperm motility by activating seminal leucocytes, which in turn induce oxidative stress on the sperm. Leucocytospermia is almost always present in HIV-seropositive men.

Adult↗

Transurethral deroofing of midline prostatic cyst for subfertile men.

We evaluated the efficacy of transurethral deroofing of a midline prostatic cyst in subfertile men with one or more of the following semen abnormalities: decreased ejaculatory volume, decreased sperm motility and oligo- or azoospermia. Results from treatment of a series of 11 subfertile men with a midline prostatic cyst by transurethral deroofing of the cyst are presented. Five patients showed an improvement of seminal volume. Only one patient demonstrated an improvement of sperm count. Sperm motility was not influenced. No relationship was found between positive outcome following operation and either size of the cyst or dilatation of the seminal vesicles. Spontaneous pregnancies did not occur after transurethral deroofing of the midline prostatic cyst. In conclusion, our study suggests a poor efficacy of transurethral deroofing of a midline prostatic cyst in subfertile men with the above mentioned semen abnormalities.

Adult↗

The result of intracytoplasmic sperm injection is not related to any of the three basic sperm parameters.

High success rates have been reported for the use of intracytoplasmic sperm injection (ICSI) in alleviating essentially andrological infertility. However, neither the relationship between any of the sperm parameters and the result of ICSI nor the minimal sperm requirements for ICSI have been investigated so far. In this paper, our objective was therefore to study the relationship between three basic sperm parameters (total sperm count, sperm motility and morphology) and the outcome of ICSI by retrospective analyses of fertilization, embryo development and pregnancy rates in 966 micro-injection cycles, performed with ejaculated semen. The results showed that there was no important influence from either the type or the extent of sperm impairment on the outcome of ICSI. Even in the most extreme cases of male-factor infertility, where cryptozoospermia or total astheno- or total teratozoospermia was diagnosed in the initial semen sample, high fertilization and pregnancy rates were obtained by ICSI. Only one condition had a strongly negative influence on the result of ICSI: where an immotile (presumably dead) spermatozoon was injected into the oocyte. Thus the only ultimate criterion for successful ICSI is the presence of at least one living spermatozoon per oocyte in the pellet of the treated semen sample used for micro-injection.

Cytoplasm↗

Lack of effects of nose-only inhalation exposure on testicular toxicity in male rats.

Reductions in testicular mass, sperm motility, and mating frequency have been attributed to the stresses caused by confinement of Sprague-Dawley male rats in nose-only inhalation exposure tubes. Testicular changes, including an increase in testicular atrophy, have been detected at an increased incidence in male rats used in inhalation studies as compared with rats of the same age and strain used in oral toxicity studies. This study was designed to determine whether nose-only exposure of male rats caused testicular toxicity under conditions of cooling of the exposure room and appropriate acclimation to the exposure tubes. In order to acclimate the rats to the nose-only inhalation exposure apparatus, all male rats were placed in the exposure tubes for at least four successively increasing time intervals (15, 30, 45, and 60 min) on 4 separate days, with a rest period of approximately 48 h between the first and second acclimation. Twenty male rats were exposed nose-only to filtered air for approximately 2 h per day for 28 days before cohabitation and continuing throughout a 14-day cohabitation period. To reduce thermal stress, the exposure room temperature was maintained at 64 to 70 degrees F. Twenty control rats were housed in the same room as the exposed rats but were not placed in exposure tubes. End points monitored were body weight, testicular weight, sperm count, sperm motility, and histopathology of the testes, epididymides, prostate, and seminal vesicles. The control rats gained weight more rapidly than the exposed rats. All the rats in both groups mated successfully, and testicular weights, normalized to body weight, were similar for both groups. More importantly, there were no microscopic changes that could be considered an adverse effect on the reproductive tissues in the male rats placed in exposure tubes. Thus, nose-only exposure for up to 2 h per day for a total of 42 days did not cause adverse effects on the reproductive organs, fertility, or reproductive performance of male rats under the conditions of this study.

Animals↗

Does exposure to di(2-ethylhexyl) phthalate in pre-pubertal boars affect semen quality post-puberty?

Di(2-ethylhexyl) phthalate (DEHP), a plastic softener used in polyvinyl chloride (PVC) products, has been ascribed to have toxic effects on animal reproduction. The present study aimed at determining potential late effects of pre-pubertal oral exposure to DEHP on semen quality in young pigs. Ten pairs of cross-bred male siblings were used. One brother in each pair became, at random, the test animal while the other acted as control. Test males were exposed to 300 mg/kg body weight (bw) of DEHP administered orally three times a week from 3 to 7 weeks of age. The control group was given placebo (water). Semen analyses started when the boars reached 6 months of age, with semen collected twice weekly, until animals were 9 months of age. Semen was evaluated for ejaculate volume, sperm concentration, total sperm count, sperm motility, sperm morphology (including presence of cells other than spermatozoa) and sperm plasma membrane integrity. Total sperm motility tended to be lower while local motility was higher in the DEHP-exposed group compared with controls (p = 0.07) when assessed by computer-assisted sperm analysis. The DEHP-exposed group had a significantly (p < 0.05) lower percentage of spermatozoa with tailless, defective heads (at 7-8 months of age) and double-folded tails (at 6-7, 7-8 and 6-9 months of age), compared with controls (albeit always under 5%). In summary, there were no obvious adverse effects of early oral exposure to 300 mg/kg bw of DEHP on sperm output and sperm quality in post-pubertal young boars.

Administration, Oral↗

alpha-1,4-Glucosidase activity in infertile oligoasthenozoospermic men with and without varicocele.

This work aimed to assess seminal alpha-1,4-glucosidase activity in infertile oligoasthenozoospermic men associated with and without scrotal varicocele. Eighty men were investigated. They were divided into three groups: group 1 (n = 20), fertile normozoospermic men; group 2 (n = 30), oligoasthenozoospermia with varicocele; and group 3 (n = 30), oligoasthenozoospermia without varicocele. The patients underwent medical history, clinical examination, conventional semen analysis and estimation of seminal plasma alpha-1,4-glucosidase activity by double-beam spectrophotometer method and serum testosterone by radioimmunoassay method. There was a significant decrease in the mean seminal alpha-1,4-glucosidase activity levels in infertile men versus controls (mean +/- SD; 7.66 +/- 0.433, 2.088 +/- 0.565, 5.384 +/- 0.85 mU ml(-1) respectively). Mean serum testosterone levels demonstrated nonsignificant differences between studied groups. Seminal alpha-1,4-glucosidase activity levels demonstrated significant correlation with sperm count, sperm motility percentage and serum testosterone in oligoasthenozoospermia with varicocele group and demonstrated nonsignificant correlation in other groups. It is concluded that varicocele-induced hypoxia is the adverse effect that causes both oligoasthenozoospermia and decreased seminal alpha-1,4-glucosidase levels.

Adult↗

Effect of dermal application of hexachlorocyclohexane (HCH) on male reproductive system of rat.

1. The toxic manifestations of dermally applied hexachlorocyclohexane (50 mg or 100 mg kg-1 body weight day-1, 5 days in a week for 120 days) on testes and sperm of rat have been investigated. 2. The results indicate that exposure of HCH through the dermal route could lead to an alteration in the activities of marker testicular enzymes viz. sorbitol dehydrogenase (SDH), glucose-6-P-dehydrogenase (G6PDH), gamma-glutamyl transpeptidase (gamma-GT) and beta-glucuronidase (beta Gluc.) associated with specific cell types. 3. Significant quantities of HCH and its isomers accumulated in testes as well as sperm of treated rats. 4. HCH exposure also led to a decrease in serum testosterone levels, epididymal sperm count, sperm motility and an increase in the percentage of abnormal sperm. 5. These observations indicate the possibility of adverse effects of HCH on the male reproductive functions of men exposed dermally to this pesticide in industry or during spraying in the field.

Administration, Topical↗