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Reversibility of the toxic effect of lead on the male reproductive axis.

The present study investigates the reversibility of the toxic effects of lead on the hypothalamic-pituitary-testicular axis in prepubertal and pubertal male rats. Male Wistar rats, 27 days and 52 days old, were given ad libitum access to 0.0% or 0.6% lead acetate containing water. Groups of animals were sacrificed at the end of 30 days of exposure or after a 30-day recovery period. Blood lead and free erythrocyte porphyrin (FEP) levels in the lead-treated groups were significantly higher than in the control animals (P less than 0.001). The animals in the recovery groups had lower, albeit not normal, blood lead and FEP levels 30 days after discontinuing treatment. Serum testosterone, intratesticular sperm counts, and sperm production rates were suppressed in the lead-treated groups (P less than 0.001). Serum testosterone and sperm parameters normalized at the end of the recovery period in the prepubertal animals but not in the pubertal animals.

Animals↗

Serum dioxin-like activity is associated with reproductive parameters in young men from the general Flemish population.

BACKGROUND: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and some related environmental contaminants are aryl hydrocarbon receptor (AhR) ligands that exert reproductive and developmental toxicity in laboratory animals. In humans, fertility-related effects are less documented. OBJECTIVE: The aim of this study was to investigate the relationship between dioxin-like biological activity in serum and parameters of reproductive status in men from the general population 5 months after a polychlorinated biphenyl and dioxin food-contamination episode in Belgium. DESIGN: In the framework of the cross-sectional Flemish Environment and Health Study (FLEHS), we recruited 101 men 20-40 years of age and evaluated sperm parameters, measured sex hormones, and gathered information on a number of lifestyle factors. In addition, we determined the AhR-mediated enzymatic response elicited by individual serum samples and expressed it as TCDD equivalent concentrations (CALUX-TEQs) using an established transactivation assay. RESULTS: Age (p = 0.04) and the frequency of fish (p = 0.02) and egg (p = 0.001) consumption were independent positive determinants of serum dioxin-like activity. After correcting for possible confounders, we found that a 2-fold increase in CALUX-TEQ > 16 pg/L was associated with a 7.1% and 6.8% (both p = 0.04) decrease in total and free testosterone, respectively. We also observed a more pronounced drop in semen volume of 16.0% (p = 0.03), whereas sperm concentration rose by 25.2% (p = 0.07). No relationship was found with total sperm count or sperm morphology. CONCLUSIONS: These data suggest an interaction of dioxin-like compounds with the secretory function of the seminal vesicles or prostate, possibly indirectly through an effect on testosterone secretion, at levels not affecting spermatogenesis as such.

Adult↗

Influence of penning type and feeding level on sexual behavior and feet and leg soundness in boars.

Ninety-six Yorkshire males at 28 d of age were placed on a pre-test feeding regimen (22% CP) of either ad libitum (A) access to feed or a restricted (R, 85% of A) diet. All pigs were housed in groups of four until approximately 30 kg body weight. The boars were then placed under test and assigned to a group pen (GP) containing eight boards or to individual pens (IP) and fed a 16% CP diet at A or R levels. Feeding types during pre-test and test phases were, therefore, ad libitum followed by ad libitum (AA), ad libitum: restricted (AR), restricted: ad libitum (RA), and restricted: restricted (RR) for each of the two (IP and GP) housing types. All boars were weighed every 2 wk to determine the feeding level and ADG. The pen floors were partly slatted with water nipples in the slatted areas. Areas available for each board were 1.63 and 2.15 m2 in IP and GP, respectively. Sexual behavior, semen characteristics, and feet and leg scores were recorded between 150 and 240 d of age. The IP boards required longer (P < .05) contact with receptive gilts before mating, made more (P < .01) ano-genital sniffings, and attempted more (P < .10) incorrect mounts than GP boars. The GP boards had a higher (P < .01) mating score, younger (P < .001) age at completion of the mating test, and lower (P < .01) total sperm count and sperm concentration (P < .001) than IP boars. The AA boards exhibited less (P < .10) chomping and salivation than boars on other feeding regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

Comparison of gonadal function between fertile and infertile men with varicoceles.

The high prevalence of men with varicoceles who by history are fertile has led some to question the suggested causal relationship between a varicocele and male infertility. However, testicular function in these fertile men has not previously been studied in detail. Fifty-five normal fertile men, 42 fertile men with varicoceles, and 24 infertile men with varicoceles and normal female partners were studied. Semen analyses were done, baseline serum testosterone and gonadotropin levels tested and the gonadotropin response to luteinizing hormone-releasing hormone (LH-RH) measured. The infertile men with varicoceles exhibited lower sperm counts, abnormal sperm morphologic features, increased baseline serum gonadotropins, and increased gonadotropin responses to LH-RH, compared with the normal fertile men. The fertile men with varicoceles showed similar abnormalities, although this was not statistically significant in all cases. That semen and hormone abnormalities were observed in both the fertile and infertile men with varicoceles suggests that the presence of a varicocele is associated with some degree of primary testicular dysfunction, regardless of present fertility status.

Adult↗

Relationship between the duration of sexual abstinence and semen quality: analysis of 9,489 semen samples.

OBJECTIVE: To evaluate the relationship between duration of sexual abstinence and various characteristics of normal and subnormal semen. DESIGN: A retrospective study based on computerized data. SETTING: Fertility and IVF unit at a university medical center. PATIENT(S): Nine thousand, four hundred eighty-nine semen samples from 6,008 patients were analyzed according to the World Health Organization (WHO) manual and grouped according to sperm concentration (10(6)/mL) into severe (0.2-4 x 10(6)), moderate (>4-10 x 10(6)), and mild (>10-19.99 x 10(6)) oligozoospermia, and normozoospermia (> or =20-250 x 10(6)) groups. MAIN OUTCOME MEASURE(S): In each group mean values of semen volume, sperm concentration, percentage of motile sperm and of normal morphology (according to WHO or Kruger criteria), total sperm count, and total motile sperm count per ejaculate were related to duration of abstinence. RESULT(S): Among the 3,506 oligozoospermic samples, the peak mean sperm motility of 30.3% was observed after 1 day of abstinence. Similarly, the mean percentage of normal morphology among mild-moderate oligozoospermic samples (n = 2,260) reached peak values of 7.4%-8.6% between 0-2 days of abstinence. The 5,983 normozoospermic samples showed a significant decrease in the percentage of sperm motility and normal morphology to mean values of 33.1% and 7.0%, respectively, on days 11-14 of sexual abstinence. CONCLUSION(S): Our data challenge the role of abstinence in male infertility treatments and suggest that to present the best possible semen samples, patients with male factor infertility should collect the semen after just 1 day of sexual abstinence. Patients presenting normal sperm analysis or sperm donors for cryopreservation purposes should be advised not to exceed 10 days of sexual abstinence.

Adult↗

Comparison of photographic (multiple-exposure photography) and conventional evaluation of ejaculates for fertility prognosis.

Semen obtained from 191 men visiting our infertility clinic was studied by MEP and conventional methods. With MEP, sperm count, percentage of motility, sperm velocity, straight line approach, and speed constancy were determined. Two years afterward 49 of the men appeared to have fertilized their partners. Between the fertile and infertile men, no differences in motility values determined by MEP could be detected. The only differences observed existed in sperm count and duration of infertility.

Humans↗

Quality assurance for sperm concentration using latex beads.

OBJECTIVE: To provide a simple, universally applicable method of quality assurance for sperm counting, thereby reducing intercounting chamber variation. DESIGN: By using a known concentration of latex beads, the sperm:bead ratio can be used to calculate the actual sperm count. MAIN OUTCOME MEASURES: The mean sperm and bead counts were determined in both a Spot-lite hemocytometer (Baxter Diagnostics, McGaw Park, IL) and a Makler chamber (Polymedco Inc., Yorktown, NY) from 21 different ejaculates mixed with a known concentration of beads. The hemocytometer chamber was used as the standard counting chamber because it consistently yielded a low variation in sperm count. The adjusted sperm concentration of the Makler chamber was calculated using the following formula [hemocytometer beads]/[Makler beads] x [Makler sperm]. RESULTS: Observed mean +/- SD sperm counts were significantly different between the hemocytometer chamber (110.6 +/- 66.2 x 10(6)/mL) and Makler chamber (173.3 +/- 103.5 x 10(6)/mL). However, calculated Makler chamber sperm counts (118.1 +/- 76.1 x 10(6)/mL) was not statistically different from observed hemocytometer sperm counts. CONCLUSION: This novel approach to sperm counting using a known concentration of latex beads as a reference material can be used to reduce variation in sperm counting between observers, counting chambers, and possibly computerized sperm analyzers.

Equipment and Supplies↗

Dose-response effects of Lepidium meyenii (Maca) aqueous extract on testicular function and weight of different organs in adult rats.

Lepidium meyenii (Brassicaceae) known as Maca grows exclusively between 4000 and 4500 m over the sea level in the Peruvian central Andes. The dried hypocotyls of Maca are traditionally used as food and for its supposed fertility-enhancing properties. A dose-response study was performed to determine the effect of 7 days oral administration of an aqueous lyophilized extract of Maca at 0.01-5 g/kg (corresponding to 0.022-11 g dry hypocotyls of Maca/kg) on body and different organ weights, stages of the seminiferous tubules, epididymal sperm count and motility, and serum testosterone and estradiol levels in rats. In doses up to 5 g extract/kg, no toxicity was observed. Almost all organ weights were similar in controls and in the Maca extract-treated groups. Seminal vesicles weight was significantly reduced at 0.01 and 0.10 g extract/kg. Maca increased in length of stages VII-VIII of the seminiferous tubules in a dose-response fashion, with highest response at 1.0 g/kg, while caput/corpus epididymal sperm count increased at the 1.0 g dose. Cauda epididymal sperm count, sperm motility, and serum estradiol level were not affected at any of the doses studied. Serum testosterone was lower at 0.10 g extract/kg. Low-seminal vesicle weights correlated with low-serum testosterone levels (R2=0.33; P<0.0001) and low-testosterone/estradiol ratio (R2=0.35; P<0.0001). Increase in epididymal sperm count was related to lengths of stages VII-VIII. Highest effect on stages VII-VIII of the seminiferous tubules was observed at 1.0 g Maca aqueous extract/kg. The present study demonstrated that Maca extract in doses up to 5 g/kg (equivalent to the intake of 770 g hypocotyls in a man of 70 kg) was safe and that higher effect on reproductive parameters was elicited with a dose of 1 g extract/kg corresponding to 2.2 g dry Maca hypocotyls/kg.

Administration, Oral↗

Effects of amitriptyline on semen of infertile men.

A clinical evaluation of the effects of the antidepressive drug amitriptyline on the semen of 20 infertile men with oligoasthenozoospermia was carried out. Quantitative assessment of semen in the whole group showed significantly higher sperm counts, an increased proportion with normal sperm morphology and an increased semen volume after treatment, with a high positive correlation between sperm count before and after treatment. Individual qualitative evaluation showed an increased sperm count in 50% and increased motility in 35% of patients. It would seem that amitriptyline has a beneficial effect on semen in some of these patients.

Adult↗

The effect of ejaculatory frequency on semen characteristics of normozoospermic and oligozoospermic men from an infertile population.

The characteristics were examined of 87 consecutive semen samples obtained from participants of an intra-uterine insemination (IUI) programme. The population investigated comprised 65 normozoospermic, 13 moderately oligozoospermic and nine severely oligozoospermic individuals. The samples were produced after 4 days abstinence for the first IUI and after a further day of abstinence for the second IUI. Semen volume, sperm concentration, total sperm count and total motile sperm count for the whole population decreased significantly between the first and second samples. The characteristics of the second sample were significantly decreased only for the normozoospermic group.

Ejaculation↗

How often should infertile men have intercourse to achieve conception?

OBJECTIVE: To clarify how often infertile men should have intercourse to achieve conception, the effect of sequential ejaculation on total motile sperm counts was investigated. DESIGN: Case-control study. SETTING: Infertility and IVF unit, tertiary care center. PARTICIPANTS: Five hundred seventy-six men who produced two closely spaced sequential ejaculates. MAIN OUTCOME MEASURE: The total motile sperm counts of the second ejaculates were compared with the total motile sperm counts of the first ejaculates. RESULTS: In normospermic men (n = 359), the total motile sperm counts decreased significantly from 93 (18 to 601) (median [minimum to maximum] x 10(6)) in the first ejaculate to 42 (1.2 to 387) in the second ejaculate, produced 24 hours later. In contrast to the normospermic men, in the asthenospermic group (24 hours difference, n = 81) and in both oligospermic groups, (1 to 4 hours difference, n = 27; and 24 hours difference, n = 45), there were no significant changes in the total motile sperm counts (24 [5.9 to 229] versus 30 [0.8 to 150], 6 [0.8 to 18] versus 3.6 [0.1 to 63] and 13 [2.5 to 32] versus 10 [0.1 to 66], respectively). Moreover, in both oligoasthenospermic groups (1 to 4 hours difference, n = 23; and 24 hours difference, n = 41) the total motile sperm counts increased significantly (3.2 [0.6 to 7.9] versus 8 [0.4 to 48] and 4 [0.2 to 13] versus 4 [0.1 to 101], respectively). In all groups, pooling sequential ejaculates significantly increased the total motile sperm counts, over and above that of the first ejaculate, by 49% in the normospermic group, 95% in the asthenospermic group, 67% and 75% in the oligospermic groups (1 to 4 hours and 24 hours difference, respectively), and 233% and 139% in the oligoasthenospermic groups (1 to 4 hours and 24 hours difference, respectively). CONCLUSIONS: Sequential ejaculation may overcome the impaired sperm transport causing low total motile sperm counts observed in some oligospermic and/or asthenospermic men. Most of these infertile men may significantly increase their fertility potential, assessed by the total motile sperm counts, either by pooling sequential ejaculates for IUI, GIFT, and IVF, or by having intercourse every day or even twice a day, at the time of ovulation.

Case-Control Studies↗

Some interrelationships between plasma levels of LH, FSH, oestradiol 17beta, androgens and semen analysis data in male infertility patients.

Serum LH, FSH and immunoreactive testosterone-like substances (TLS) have been measured by radioimmunoassay in 130 male infertility patients and oestradiol 17beta in 26 cases. A weak but significant negative correlation was found between FSH and sperm count (rs = -0.19, p less than 0.05) but not LH and sperm count. However, LH and FSH were strongly correlated in the azoospermic (rs = 0.71, p less than 0.01) and oligozoospermic (rs = 0.53, p less than 0.01) groups and levels of both gonadotrophins were significantly elevated in the azoospermic and oligozoospermic as compared to the normozoospermic group. The elevated LH levels in the oligozoo- and azoospermic groups could not be explained by reduced negative feedback of testosterone or oestradiol 17beta since firstly, TLS and oestradiol 17beta levels were similar in all three groups and, secondly, within-group correlations between LH and TLS were either non-significant or positive (azoospermic group r = 0.37, p = 0.06). It is suggested that spermatogenesis-related feedback factor(s) may inhibit LH as well as FSH secretion. No role for oestradiol 17beta as a selective inhibitor of FSH secretion seemed likely as oestradiol 17beta levels were similar in the three groups and were correlated (r = 0.51, p less than 0.01) to TLS levels i.e. to leydig cell rather than spermatogenic function. Seminal fructose was negatively correlated (r = -0.26, p less than 0.01) with sperm count but not significantly with plasma TLS. It would thus seem unlikely that the tendency for seminal fructose levels to increase as sperm count decreases is due to increased androgen production or that seminal fructose can be used as an index of a patient's androgenic status. Patients with varicoceles had hormone levels similar to other patients of similar sperm count. Both sperm morphology and motility were strongly correlated to log sperm count (r = 0.84 and 0.55 respectively) and semen volume was significantly greater in oligozoospermic than normozoospermic patients (p less than 0.01).

Androgens↗

[Treatment of male infertility with clomiphene citrate (author's transl)].

Ninety unselected male patients with infertility were treated with clomiphene citrate, 25 mg/day, taken on 20 consecutive days each month for a period of 3 to 12 months. The patients were divided into two groups according to sperm counts. In 39 cases of oligozoospermia with sperm counts above 10 million/ml, six pregnancies were obtained (15.4%) while a significant improvement of sperm counts occurred in 22 cases (56.4%). On the other hand, in 51 cases with azoospermia or oligozoospermia below 10 million/ml only three pregnancies occurred (5.9%) and two patients (3.9%) had significantly improved sperm counts. The indications and form of administration of clomiphene citrate are commented upon.

Clomiphene↗

[Numerical chromosome anomalies in human sperm at low sperm concentration].

INTRODUCTION: With the assisted reproduction techniques the natural selection of sperm is bypassed on different levels. AIM: The aim of the present work is to determine the frequencies of sperm numerical chromosome aberrations in infertile men with low sperm count and to examine the relationship between the spermatogram parameters (sperm count and motility) and the aneuploidy and diploidy frequencies. METHODS: 32 men with low sperm count were investigated. Semen analysis was performed according to the WHO criteria. Disomy and diploidy frequencies were detected with fluorescence in situ hibridization using 17, X and Y centromeric probes. 200,969 sperm were scored, with the mean of 6272 cells in each subjects. The rate of numerical chromosome anomalies were also estimated using the detected disomy and the diploidy frequencies. RESULTS: Mean sperm concentration of the 32 men was 18.2 million/ml (SD: +/- 8.43, range: 8.0-45.5), mean motility 49.4% (+/- 9.32, 30-69.2). The X/Y ratio was 1.07. The mean frequencies of sex chromosome disomy, chromosome 17 disomy and diploidy were 0.36%, 0.16% and 0.56%, respectively. The most frequent disomy was XY disomy (0.14). Sex chromosome disomy frequencies were higher in oligospermic samples (0.37% vs. 0.32%, OR = 1.18, 95% CI = 1.01-1.39, p < 0.001). With special regard to XY disomy (0.08% vs. 0.17%, OR = 1.99, 95% CI = 1.48-2.67, p < 0.001). In subjects with oligoasthenozoospermia the diploidy frequency increased (0.96%, OR = 2.39, 95% CI = 2.13-2.69, p < 0.001), mostly due to the elevated rate of diploid sperm of meiosis II. origin (XX or YY diploids). Estimated frequency of the numerical chromosome anomalies was 8.3 +/- 5.3 in the study population. Neither the sperm count, nor the sperm motility showed correlation with the detected frequency of the chromosome aberrations. CONCLUSIONS: In oligospermic patients there is a risk for elevated frequency of sperm with sex chromosome aneuploidy, especially the XY disomy. Furthermore, the diploidy frequency is increased in oligozooastenospermic samples. Nevertheless, classical parameters of semen analysis (sperm count and motility) do not correlate with the frequency of numerical chromosomal anomalies. The risk can be determined using fluorescens in situ hybridization on sperm.

Chromosome Aberrations↗

Effect of human dietary exposure levels of genistein during gestation and lactation on long-term reproductive development and sperm quality in mice.

The objective of the present study was to determine the long-term reproductive effects of gestational and lactational exposure (0, 0.1, 0.5, 2.5 and 10 mg/kg/day) to genistein on male mice at levels comparable to or greater than human dietary exposures. Testicular growth, sperm count and motility, and sperm fertilizing ability in vitro was assessed in male offspring on postnatal days (PND) 105 and 315. Selected genes were also examined by real-time PCR to determine whether genistein caused changes in gene expression similar to those previously observed with diethylstilbestrol (DES). No significant treatment-related effects on male offspring body weight, anogenital distance, seminal vesicle weight or testis weight were observed. There were also no significant effects on sperm count, the percent of motile sperm or the number of motile sperm at any age. The in vitro fertilizing ability of epididymal sperm was increased significantly in the high-dose group approximately 17% (P < 0.001) on PND 105 and 315. The results indicate that developmental exposure of mice to genistein at human exposure levels does not induce adverse effects on sperm quality or changes in testicular gene expression similar to DES.

Animals↗

Human chorionic gonadotropin free beta-subunit in the human seminal plasma: a new marker for spermatogenesis?

UNLABELLED: In the past 20 years, several factors were detected in the human seminal plasma and proposed as markers for spermatogenesis. Human chorionic gonadotropin (hCG) and its beta-subunit were therefore investigated, and their seminal levels were found to be higher than those detected in the serum and to correlate with sperm parameters. OBJECTIVE: We designed a retrospective study to determine the suitability of hCG free beta-subunit concentration in the seminal plasma of fertile and infertile male patients as marker of spermatogenesis. STUDY DESIGN: A total of 79 infertile male patients were divided into four groups by their semen analysis results (group 1 [n=8]: azoospermia; group 2 [n=21]: severe oligozoospermia; group 3 [n=40]: oligoasthenospermia (OAS); group 4 [n=10]: asthenospermia) and 10 healthy volunteers of proven fertility were evaluated. RESULTS: The hCG free beta-subunit levels in the seminal plasma were found to be significantly higher (P<0.0001) in the control group in respect to those assayed in the infertile patients and showed a correlation with sperm count (r=0.5) and total motile sperm density (r=0.5). Twenty-five patients were on treatment with oral Mesterolone (100mg daily) plus Tamoxifen (20mg daily) for 3-6 months. Apart from a significant improvement (P<0.05) in sperm morphology, no significant changes in sperm count and motility were observed after the treatment in all the patients. In the seminal plasma of 10 patients who showed a significant increase in sperm count, hCG free beta-subunit levels were found to be significantly higher compared to those detected in the remaining patients (P<0.01). In all patients, these levels remained unchanged after the treatment. CONCLUSIONS: The evidence regarding the positive correlation between hCG free beta-subunit levels in the seminal plasma and sperm concentration is consistent with the previous results regarding hCG levels. A previous study demonstrated that testosterone levels in seminal plasma correlated with sperm concentrations; from the same evidence regarding hCG we hypothesize that seminal plasma testosterone and hCG levels are correlated. Thus, hCG may play a paracrine role in the intratesticular regulation of testosterone secretion.

Adult↗

Effect of reactive oxygen species produced by spermatozoa and leukocytes on sperm functions in non-leukocytospermic patients.

OBJECTIVE: To investigate whether there is an impact of different sources of reactive oxygen species (ROS) on sperm functions. DESIGN: Prospective study. SETTING: Patients at the Center for Dermatology and Andrology, Giessen, Germany. PATIENT(S): Semen collected from 63 randomly collected patients attending the IVF unit of the University of Giessen, Germany. INTERVENTION(S): Only patients with nonleukocytospermia were included in this study. MAIN OUTCOME MEASURE(S): Sperm count and motility before and after sperm separation by swim-up, morphology, DNA fragmentation, and extrinsic (by leukocytes) and intrinsic ROS production (by spermatozoa) were evaluated. RESULT(S): Leukocytes correlated significantly with extrinsic ROS production (r = 0.576), but markedly less with intrinsic ROS production (r = 0.296). Sperm count, morphology, and motility in the ejaculate were markedly more affected by extrinsic than by intrinsic ROS. The DNA fragmentation was strongly positively correlated with intrinsic ROS production, whereas this correlation was weaker for extrinsic ROS production. No correlation was found between DNA fragmentation and the number of leukocytes, whereas the correlations with motility in the ejaculate and the motile sperm count after swim-up were highly significant. Moreover, significant differences were observed for extrinsic and intrinsic ROS production between groups of patients having a high (> or = 1 x 10(6)/mL) and a low number (<1 x 10(6)/mL) of leukocytes in the ejaculate. CONCLUSION(S): The origin of ROS seems to have an influence on the site of the damage. Because leukocyte counts <1 x 10(6)/mL caused a significant decrease of motility and DNA integrity, the threshold given by the World Health Organization (WHO) should be re-evaluated.

Adult↗

Environment, lifestyle and male infertility.

Our understanding of the importance of environmental and lifestyle factors on sperm count and fertility is constrained by the extreme variation in sperm count between men and between ejaculates. The factors responsible for this variation provide a key to understanding what factors actually affect the sperm count. The relative importance of the various factors and the pathways via which they affect sperm count are discussed. The most important are Sertoli cell number, ejaculatory frequency, season, factors affecting scrotal heating (e.g. the time spent seated), a past history of reproductive tract disorders and ageing. The possible role of other environmental factors commonly supposed to affect sperm count (exposure to pesticides or endocrine disruptors) is discussed, although the evidence for a major influence of such factors is lacking. It is suggested that lifestyle changes, especially in the time spent seated, will exert an adverse effect on sperm production in a progressively larger group of men over the next decade.

Demography↗