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Lead exposure causes generation of reactive oxygen species and functional impairment in rat sperm.

The relationships between blood lead, sperm lead, sperm reactive oxygen species (ROS) level, and sperm fertile capability were investigated to understand the effects of lead exposure on sperm function and the mechanism of these effects. Male Sprague-Dawley rats, 7 weeks old, were randomly divided into control group and lead-treated group. The controls and lead-treated animals received intraperitoneal injection of 10 mg sodium acetate and 10 mg lead acetate/kg body weight, respectively, weekly for 6 or 9 weeks. The blood lead and epididymal sperm lead were analyzed by graphite furnace atomic absorption spectrophotometer. Chemiluminescence was measured to evaluate the generation of sperm ROS. Sperm-oocyte penetration rate (SOPR) was measured to evaluate sperm function. After 6 weeks of lead exposure, the rats had average blood lead levels of 32 microg/dl, sperm lead levels of 0.67 +/- 0.11 microg/10(9) sperm, unchanged epididymal sperm counts, percent of motile sperms, and motile epididymal sperm counts compared with control animals. However, after 9 weeks of lead exposure, the rats had average blood lead levels of 48.0 +/- 4.3 microg/dl, sperm lead levels of 0.88 +/- 0.16 microg/10(9) sperm, statistically lower epididymal sperm counts, and lower motile epididymal sperm counts. There was a good correlation between the blood lead and sperm lead(r2 = 0.946, P < 0.001). The sperms of lead-exposed rats produced significantly higher counts ofchemiluminescence than did those from the control rats (P < 0.001). The chemiluminescence counts were positively associated with sperm lead level (r2 = 0.613, P < 0.001). Epididymal sperm counts, motility and motile epididymal sperm counts were negatively associated with sperm chemiluminescence (r2 = 0.255, 0.152, and 0.299; P < 0.01, 0.05, and 0.01, respectively). The SOPR were positively associated with epididymal sperm counts, motility and motile epididymal sperm counts (r2 = 0.136, 0.285, and 0.264; P < 0.05, 0.01, and 0.001, respectively). The sperm chemiluminescence was negatively associated with SOPR (r2 = 0.519, P < 0.001). It is concluded that lead exposure probably affected the sperm function by activating one of the pathways of ROS generation.

Animals↗

Lepidium meyenii (Maca) improved semen parameters in adult men.

AIM: The present study was designed to determine the effect of a 4-month oral treatment with tablets of Lepidium meyenii (Maca) on seminal analysis in nine adult normal men aged 24-44 years old. METHODS: Nine men received tablets of Maca (1500 or 3000 mg/day) for 4 months. Seminal analysis was performed according to guidelines of the World Health Organization (WHO). Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), testosterone (T) and estradiol (E2) were measured before and after treatment. RESULTS: Treatment with Maca resulted in increased seminal volume, sperm count per ejaculum, motile sperm count, and sperm motility. Serum hormone levels were not modified with Maca treatment. Increase of sperm count was not related to dose of Maca. CONCLUSION: Maca improved sperm production and sperm motility by mechanisms not related to LH, FSH, PRL, T and E2.

Adult↗

[Andrological, biochemical and endocrinological studies of subfertile men during kallikrein therapy].

31 men with idiopathic oligozoospermia and 23 men with idiopathic asthenozoospermia were treated three months by oral administration of daily 600 units kallikrein. In a greater number of patients apart from the semen analysis different seminal plasma proteins and enzymes as well as hormones in serum (LH, FSH, prolactin, testosterone) and in seminal plasma (LH, prolactin) were determined. There was a significant increase of sperm count and sperm motility in the oligozoospermic group. In asthenozoospermic patients sperm motility was significantly increased, however, sperm count decreased within the normal range. Conception rate was 25% in the oligozoospermic goup and 36% in the asthenozoospermic group. A treatment period of three months showed better results than seven weeks and a dosage of 600 units kallikrein daily was significantly better than daily 300 units. During kallikrein therapy mean concentrations of alpha U,x-antichymotrypsin in seminal plasma and serum LH, prolactin and testosterone increased significantly. Seminal plasma levels of LH and prolactin remained unchanged. The mode of action of systemic kallikrein therapy may be at the level of tissue hormones (kinin liberation), however, an increase of the intratesticular testosterone level and an interference with the blood-seminal plasma barrier has also to be considered.

Follicle Stimulating Hormone↗

Effects of exposure to genistein and estradiol on reproductive development in immature male mice weaned from dams adapted to a soy-based commercial diet.

Genistein, a soybean-originated isoflavone, is widely consumed by humans for putative beneficial health effects but its estrogenic activity may adversely affect the development of male reproductive system. Twenty one-day-old ICR mice weaned from dams fed with a soybean-based diet throughout gestation and lactation were exposed by gavage to genistein (2.5 mg/kg b.w./day) or 17beta-estradiol (7.5 microg/kg b.w./day) for five weeks. Corn oil was used as a negative control. The animals were fed with a casein-based AIN-76A diet throughout the experimental periods. There were no significant differences in body and organ weights of mice among experimental groups. No significant differences in sperm counts and sperm motile characteristics were found between control and genistein groups. Treatment of 17beta-estradiol caused a significant decrease in prostate weight and epididymal sperm counts compared to the control (p<0.05). The levels of phospholipid hydroxide glutathione peroxidase in the testis and prostate of mice exposed to genistein or 17beta-estradiol were significantly higher than that of the control mice (p<0.05). 17beta-estradiol treatment caused degeneration and apoptosis of germ cells in the testis, depletion and degeneration in the epididymal epithelium, and hyperplasia of mucosal fold region in the prostate of mice. Genistein treatment did not cause any lesion in the testis, epididymis, and prostate. These results suggest that dietary uptake of genistein during juvenile period may not affect male reproductive development and functions.

Animal Feed↗

Correlation between seminal carnitine and functional spermatozoal characteristics in men with semen dysfunction of various origins.

BACKGROUND AND OBJECTIVE: L-carnitine is an essential molecule involved in mitochondrial metabolism, controlling the transport of acetyl and acyl groups across the mitochondrial inner membrane. Carnitine and acetylated carnitine (L-acetylcarnitine) are found in high concentrations in the epididymis, where they also act as antioxidants, protecting spermatozoa against damage caused by reactive oxygen species. In this open study we investigated the correlation between seminal carnitine levels and spermatozoal function, and the effect of combined L-carnitine + L-acetylcarnitine therapy, in infertile men. PATIENTS AND METHODS: 170 infertile men were enrolled in this study. Patients were divided into those with a total sperm motility below the normal WHO range (<50% motility, group 1 [n = 102]) and those with total sperm motility within the normal range (> or =50% motility, group 2 [n = 68]). Patients in group 1 were further divided into two groups: those with primary or secondary azoospermia (1B [n = 36]), and those without (1A [n = 66]). Patients in group 1A received L-carnitine 1 g/day and L-acetylcarnitine 500 mg twice daily for 6 months. Seminal carnitine levels were measured and correlated with sperm count and motility, eosin test, hypo-osmotic swelling test, acridine orange test for sperm nuclear DNA integrity and sperm kinetics evaluated by computer-assisted sperm analysis in all patients. RESULTS: There was a significant correlation between seminal carnitine concentration and sperm concentration, total sperm count, sperm total motility, rapid forward progression, live sperm count, membrane function, nuclear DNA integrity, capacity for cervical mucus penetration, linearity of spermatic movement, and amplitude of lateral sperm head movement (all p < 0.0001) in the entire study population. In group 1A, there was a significant increase in total motility, live sperm count, membrane integrity and linearity of spermatic movement after 3 and 6 months of L-carnitine/L-acetylcarnitine treatment, and in capacity for cervical mucus penetration after 6 months of treatment, compared with baseline. CONCLUSION: Seminal carnitine concentration may be an appropriate marker of sperm and epididymal function. L-carnitine/L-acetylcarnitine treatment may be an effective therapy to improve mainly functional seminal parameters.

Acetylcarnitine↗

Infertile couples with normal counts who require subzonal sperm insertion possess a fertility defect that affects zona pellucida penetration.

The results of subzonal sperm insertion (SUZI) have been retrospectively analysed in a subset of patients with normal sperm counts who were found to require SUZI because of poor or absent fertilization of zona-intact oocytes. This patient group is of particular interest because male factor-related infertility cannot be due to insufficient numbers of spermatozoa reaching the oocytes. Thus, failed fertilization can be attributed to deficiencies in one or more steps in the fertilization process, and SUZI provides a method of distinguishing defects of zona pellucida penetration from gamete fusion. A total of 26 such patients were treated identically to and concurrently with a much larger group of SUZI candidates who typically suffered from oligozoospermia, and fertilization results were compared. Fertilization rates after SUZI were higher in patients with normal counts than in oligozoospermic patients (51 and 26% respectively), indicating that the proportion of spermatozoa capable of fusing with the oocyte is the same or higher in the group with normal counts. In addition, nearly all SUZI procedures led to fertilization (23/26), with two out of three failed fertilizations occurring in cases where two or less oocytes were manipulated, results which further indicate that failed fertilization in these patients is not due to a defect at the level of gamete fusion. These findings suggest that infertility in these patients is based upon the inability of the spermatozoa to reach the oolemma and thus, that their fertility defect resides at the step of zona penetration.

Adult↗

The reversibility of sperm quality after discontinuing nandrolone decanoate in adult male rats.

AIM: To investigate the reversibility of the effect of nandrolone decanoate (ND) on sperm parameters after discontinuing the drug. METHODS: Three groups of rats received peanut oil (control), low and high doses of ND for 14 weeks, respectively. Each group was divided into subgroups A and B, in which rats were killed 14 and 28 weeks after initiating the injection, respectively. RESULTS: Sperm count and motile sperm fraction were decreased in the subgroups A and B that received low and high doses of ND in comparison with the controls A and B, respectively. The sperm count and motile sperm fraction increased in the subgroups B that received low and high doses of ND in comparison with their corresponding subgroups A. The number of normal morphology sperm was decreased significantly in subgroups A receiving low and high doses of ND in comparison with the control subgroup A. However, this parameter was not decreased in subgroups B receiving low and high doses in comparison with the control subgroup B. The normal sperm morphology did not show any significant differences in the subgroups B in comparison with their corresponding subgroups A. CONCLUSION: The 14-week injection of low and high doses of ND decreases sperm quality and quantity in rats. These parameters were improved after discontinuing ND, but not recovered completely even when they are left untreated for 14 weeks.

Anabolic Agents↗

Induction of antifertility with lupeol acetate in male albino rats.

The present study was undertaken to evaluate the antifertility activity of the active principle, i.e. lupeol acetate, isolated from benzene extract of Alstonia scholaris in male albino rats. The treatment with lupeol acetate at the dose level of 10 mg/rat/day did not cause any significant change in the body weights, but significant reduction in the weight of reproductive organs, i.e. testes, epididymides, seminal vesicle and ventral prostate, was observed. Testicular sperm count, epididymal sperm count and motility were found significantly declined when compared with controls, which resulted in reduction of male fertility by 100%. Arrest of spermatogenesis was noted at various stages with production of primary spermatocytes (preleptotene and pachytene), secondary spermatocytes and step-19 spermatids were decreased by 52.36, 54.91, 55.67 and 69.65%, respectively. The seminiferous tubules appeared reduced in size by 24.62%. Cross-sectional surface area of Sertoli cells as well as their counts were found to be significantly depleted. Leydig cell nuclear area and number of mature Leydig cells were decreased by 27.65 and 35.47%. Biochemical parameters of tissues i.e. protein, sialic acid, glycogen and cholesterol content of testes and seminal vesicular fructose also showed significant reduction.

Alstonia↗

Effects of ethanol treatment on epididymal secretory products and sperm maturation in albino rats.

Alcoholics are often associated with fertility disturbances with low sperm count and impaired sperm motility. Spermatozoa attains forward motility and fertilizing capacity during their transit through the epididymis. Epididymal secretory products form a suitable microenvironment, which favors sperm maturation. To study the effects of ethanol on epididymal sperm maturation, ethanol (3 g/kg body weight as 25%, v/v) was given by gastric intubation twice daily for 30 days, and in another group, rats given treatment for 30 days were withdrawn of treatment for a further period of 30 days to assess the reversibility of ethanol-induced changes. Serum and epididymidal testosterone and dihydrotestosterone (DHT), epididymidal tissue and sperm carnitine, acetyl carnitine, glycerylphosphoryl choline (GPC), and sialic acid were studied along with epididymidal sperm count and cauda epididymidal sperm motility. Ethanol treatment significantly reduced the epididymal tissue/sperm carnitine, acetyl carnitine, GPC, and sialic acid, suggesting its adverse effect on these secretory products. Impaired cauda epididymidal sperm motility and fertility (in vivo) of ethanol-treated rats imply the defective sperm maturation. All these changes were reverted back to normalcy after withdrawal of ethanol treatment, indicating the transient effects of ethanol. In conclusion, it is evident that ethanol has an adverse effect on sperm maturation, which may be affected due to the decrease in serum/epididymal testosterone and DHT level and epididymal secretory products.

Acetylcarnitine↗

Seminal plasma zinc levels and sperm motion characteristics in infertile samples.

BACKGROUND: Zinc (Zn) in seminal plasma stabilizes the cell membrane and nuclear chromatin of spermatozoa. It may also have an antibacterial function. However, extremely high concentrations of Zn (10 to 100 x the normal range) may inhibit sperm motility and the function of the mannose receptor on the sperm head. In this study, we analyzed the correlation between Zn levels in seminal plasma and the characteristics of semen as measured by conventional and computer aided sperm analysis (CASA). METHODS: One hundred fifteen infertile couples were recruited for conventional semen analysis and CASA from December 1995 through January 1996, and Zn levels in semen samples were determined by flame atomic absorption spectroscopy (AAS). RESULTS: A good correlation in a positive direction (r = 0.73, p = 0.0001) was noted between the total amount of Zn per ejaculate and the Zn concentration. The Zn concentration in seminal plasma was negatively correlated with the seminal pH (r = -0.35, p = 0.0081). There was no significant correlation between the total amount of Zn per ejaculate and sperm characteristics, including sperm count, motility (% sperm count), progressive motility (% motility), rapid motility (% motility), average path velocity (VAP, microns/s), straight-line velocity (VSL, microns/s), curvilinear velocity (VCL, microns/s), amplitude of lateral head displacement (ALH, microns), beat/cross frequency (BCF, beats/s), straightness (STR), and linearity (LIN). There was also no significant correlation between the Zn concentration in seminal plasma and the above sperm characteristics. CONCLUSION: The characteristics of semen as determined by conventional semen analysis or CASA bore no correlation with total seminal Zn amount or Zn concentrations in the ejaculates. Routine determination of the Zn concentration in seminal plasma offers no advantages in infertility work-ups.

Humans↗

Selection of oligozoospermic men for tamoxifen treatment by an antiestrogen test.

In a retrospective study 46 men with idiopathic normogonadotropic oligozoospermia were treated by 20 mg Tamoxifen daily for a period of 6 months. A significant improvement of sperm count, total sperm output, total and progressive motility as well as sperm morphology was observed. In 25 men before initiation of treatment a short-term antiestrogen test with daily 40 mg Tamoxifen for a period of one week was performed with assessment of serum levels of testosterone, LH and FSH before and afterwards. Considering hormonal response in those patients who showed a more than 50% increase of sperm count (responders), FSH levels after Tamoxifen administration were unaffected. In contrast, a significant increase of the FSH level was observed in the group of the non-responders. Serum testosterone and LH levels increased in both groups, but showed no obvious differences. A similar hormonal pattern was found in father's and nonfather's concerning the response of FSH after Tamoxifen administration. It is concluded that the response of FSH towards Tamoxifen may be of use to predict improvement of semen parameters and therefore seems to be suitable to select patients for Tamoxifen therapy.

Adult↗

Extremely low seminal lead concentrations and male fertility.

Seminal lead concentrations in normal and vasectomized males with no history of lead exposure were measured by flameless atomic absorption spectrophotometry. Extremely low concentrations of 3.8 micrograms/dl were found in normal males versus 4.1 micrograms/dl in vasectomized males. No significant correlation between lead and sperm count or sperm motility existed. It is suggested that the major contribution of lead in human semen is from the prostate and/or seminal vesicles and that very low lead levels may not have measurable effect on fertility indices.

Adult↗

The effects of radiation dose-rate and quality on the induction of dominant lethals in mouse spermatids.

Hybrid male mice were given 3 Gy (300 rad) doses of X- or gamma-irradiation at dose-rates of either 0.6 or 0.002 Gy/min for each radiation. Germ-cells treated as spermatids were tested for dominant lethality. Effects on spermatogonia were evaluated by studying testis-weight, sperm-count and sperm abnormalities. The rate of induction of dominant lethal mutations was 2.1 times as high after acute X-irradiation as after protracted gamma-irradiation. Most of this difference resulted from the change in radiation quality, since the relative effectiveness of X- versus gamma-irradiation was 1.9 at low and 1.6 at high dose rates. For each radiation, however, fewer dominant lethals were induced at low dose-rates than at high (low/high ratios of 0.8 and 0.9 respectively) although differences did not reach a significant level. There were no statistically significant effects of dose rate on testis-weight or sperm-count in the X-ray series, but there were significantly less severe effects on both with protraction of the gamma-irradiation. Evidence for effects of radiation quality on these characters was conflicting. Frequencies of abnormal spermatozoa were markedly increased 7 weeks after irradiation but there were no consistent effects of radiation intensity or quality.

Animals↗

High percentage of abnormal semen parameters in a prevasectomy population.

OBJECTIVE: To evaluate semen characteristics, testicular volume, and hormonal levels of normal fertile men requiring vasectomy for sterilization. DESIGN: Retrospective study. SETTING(S): Academic medical centers. PATIENT(S): A total of 889 patients underwent a vasectomy for sterilization. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen volume, sperm concentration, motility, and morphology according to the World Health Organization (WHO); complex motion parameters evaluated by computer-assisted semen analyzer; FSH, LH, and T levels; and both testicular volumes. RESULT(S): When compared with the WHO values, 87.2% of the patients presented normal sperm morphology below the normal level. The other semen parameters (semen volume, pH, sperm concentration, and sperm motility) differed from the WHO parameters in 6%-32.2% of patients. Semen volume and sperm concentration presented a progressive increase according to the duration of sexual abstinence. However, patients with 5 days or more of abstinence had a decrease in sperm motility. Mean testicular size had the strongest correlation with serum FSH levels, total sperm count, and sperm concentration. CONCLUSION(S): Low sperm motility and morphology were found in men who request a vasectomy for sterilization. Semen volume and sperm concentration present a progressive increase and sperm motility a decrease according to the duration of sexual abstinence. Sperm concentration had stronger correlations with testicular size than did sperm quality. Therefore, the WHO normal values need to be reconsidered.

Adult↗

A comprehensive evaluation of the testicular toxicity of dichlorvos in Wistar rats.

Assessments of the reproductive toxicity of organophosphorus insecticides are important public health issues. This study aimed at defining the testicular toxicity of dichlorvos (DDVP) since this toxicity was suspected by our previous survey on pesticide sprayers and in some earlier publications during the 1970s. Ten-week-old Wistar rats were divided into four groups (n=8 or 9) and were injected subcutaneously with DDVP (0, 1, 2 or 4 mg/kg) 6 days a week for 9 weeks. After that period, erythrocyte cholinesterase (ChE) activities decreased dose-dependently, showing 44-55% inhibition among the treated groups. No significant difference was observed in the reproductive organ weights in any treated groups compared with the control group. Sperm motility decreased slightly but significantly in the 1 and 4 mg/kg groups, and significant regressions were observed between sperm motility and both blood ChE activity and urinary concentration of dimethyl phosphate (DMP), a urine metabolite of DDVP. However, sperm counts and sperm morphology in the cauda epididymidis, plasma testosterone concentrations, and histopathology in the testes in all the treated groups were not significantly different from those of the control group. Since only the sperm motility deteriorated by DDVP exposure at doses inducing marked inhibition of cholinesterase activities in the rats, it was suggested that the risk of testicular dysfunction posed to occupationally exposed humans would be small in terms of the effect of DDVP exposure alone. This conclusion was also supported by an estimate of the decrease in human sperm motility based on the urinary DMP concentrations observed in actual occupational settings.

Animals↗

High level of noncollagenous protein of spermatic vein in patients with varicocele.

Spermatic vein specimens were removed from 46 patients with varicocele who underwent high ligation of the left spermatic vein and 11 men with renal cancer who underwent radical nephrectomy. Semen analysis was performed preoperatively and after 3 months, and the contents of noncollagenous protein, collagen and elastin in the spermatic vein were determined. The noncollagenous protein contents in the spermatic vein were greater in patients with grades 2 and 3 varicocele than in those with renal cancer (p < 0.001) and grade 1 varicocele (p < 0.01), respectively. Similar results, to a lesser extent, were also obtained for the contents of collagen. The content of elastin in each group was identical. Noncollagenous protein content correlated inversely with sperm count and sperm motility in all varicocele groups, as did collagen content in patients with grades 2 and 3 varicocele. These results indicate that there is an association between a large amount of noncollagenous protein and collagen in the spermatic vein and deterioration of the spermiogram in patients with grades 2 and 3 varicocele.

Adolescent↗

Significance of testicular size measurement in andrology: II. Correlation of testicular size with testicular function.

The testicular sizes of 305 men were measured by a recently developed orchidometer and related to 9 other known parameters of testicular function. Mean testicular size had the strongest correlation with serum follicle-stimulating hormone levels, total sperm count and sperm concentration, while a significant correlation also was noted with sperm motility, percentage of live sperm, sperm morphology (normal and immature forms), and serum luteinizing hormone and testosterone levels. Sperm quantity had stronger correlations with testicular size than did sperm quality, although both were impaired in testes smaller than 14 ml. It is concluded that the size of the testis bears a direct correlation with testicular function and, thus, it can be helpful to assess rapidly andrological status during the initial physical examination.

Adult↗

Antifertility effect of chronically administered Martynia annua root extract on male rats.

The effects of 50% ethanol extract of Martynia annua L. root on reproduction was studied on male rats. The study was divided into four groups of five animals each. The first group (I) received vehicle alone to serve as control. The second, third and fourth groups (II, III and IV) of animals were administered the root extract daily at 50 mg/kg body weight, po, 100 mg/kg body weight, po, and 200 mg/kg body weight, po, respectively, for a period of 60 days. Significant decreases in the weights of testes, epididymides, seminal vesicle and ventral prostate were observed. A dose related reduction in the testicular sperm count, epididymal sperm count and motility, number of fertile males, ratio between delivered and inseminated females and number of pups were observed. The testis showed a clear correlation between the dose and severity of lesions of seminiferous epithelium. In general, the seminiferous tubules appear reduced in size with a frequently filled eosinophilic material. Spermatogenesis arrested at the secondary spermatocyte stage. Pachytene spermatocytes were undergoing degeneration. Disorganisation and sloughing of immature germ cells were visible. Leydig cells were atrophied. No morphological changes were observed in Sertoli cells. Significant reduction in serum concentration of luteinising hormone and testosterone were observed. No distinct change in serum FSII concentration was recorded. The final body weights of all groups were elevated markedly. No alterations were recorded in any hematological parameters. It is concluded that the 50% ethanol extract of M. annua root produced dose related effects on male reproduction without altering general body metabolism.

Animals↗