Reduced Semen Quality Research Articles

The hazardous effects of tobacco smoking on male fertility.

The substantial harmful effects of tobacco smoking on fertility and reproduction have become apparent but are not generally appreciated. Tobacco smoke contains more than 4000 kinds of constituents, including nicotine, tar, carbonic monoxide, polycyclic aromatic hydrocarbons, and heavy metals. Because of the complexity of tobacco smoke components, the toxicological mechanism is notably complicated. Most studies have reported reduced semen quality, reproductive hormone system dysfunction and impaired spermatogenesis, sperm maturation, and spermatozoa function in smokers compared with nonsmokers. Underlying these effects, elevated oxidative stress, DNA damage, and cell apoptosis may play important roles collaboratively in the overall effect of tobacco smoking on male fertility. In this review, we strive to focus on both the phenotype of and the molecular mechanism underlying these harmful effects, although current studies regarding the mechanism remain insufficient.

17 EFFECT OF LOCAL TREATMENT OF SEMINAL VESICULITIS ON THE QUALITY OF EQUINE FRESH SEMEN

Stallions affected by seminal vesiculitis present history of infertility or subfertility, ejaculatory disturbance, spread of sexually transmitted pathogens, and changes in semen characteristics, leading to reduced semen quality and longevity. The aim of this study was to evaluate the semen quality of stallions with seminal vesiculitis before and after local treatment. Five stallions with a mean age of 12.4 years diagnosed with seminal vesiculitis were used. The identification of the microorganism involved in the pathogenesis of seminal vesiculitis of each animal was performed by bacterial culture of the seminal vesicles flush with Ringer Lactate solution, performed in duplicate at 1-week intervals. After identification of bacteria was performed, there was susceptibility testing to antibiotic (antibiogram) and the appropriate antibiotic was chosen. The local treatment was performed by endoscopy for 10 consecutive days, and this consisted of flushing with Ringer Lactate solution, followed by infusion of the antibiotic selected. The semen analyses were performed before starting the local treatment for seminal vesiculitis (M0), after a week (M1), and after a month (M2) of therapy. Sperm kinetics were performed by computerized method – CASA for the following parameters: percentage of sperm with total motility, progressive motility, and rapid sperm. Analysis of plasma membrane integrity was performed by epi-fluorescence microscopy, using the combination of fluorescent probes carboxyfluorescein diacetate and propidium iodide. Percentage of leukocytes was assessed through evaluation in light optical microscopy of semen smears stained with DiffQuick. The content of nitric oxide (NO) was determined by colourimetric Griess reaction by a spectrophotometer through the concentrations of nitrate (NO3–) and nitrite (NO2–). To perform the count of colony forming units per millilitre (CFU mL–1), an aliquot of 0.1 mL of semen was diluted in 9.9 mL of saline. A 0.1-mL aliquot of this sample was plated on Mueller-Hinton agar. The seeded plates were incubated, and the bacterial colonies were counted after 24 h. According to the performed dilution, total colonies identified corresponds to ×10 000 CFU mL–1. The data were analysed by two-way ANOVA followed by Tukey's test (P < 0.05). The values (mean ± standard error) of seminal parameters on M0, M1, and M2 were the following, respectively: sperm kinetics (total motility: 46.5 ± 5.13a; 75.1 ± 3.42b; 42.8 ± 5.28a; progressive motility: 19.3 ± 3.86a; 33.4 ± 2.39b; 16.5 ± 2.40a; rapid sperm: 22.2 ± 1.82a; 52.2 ± 5.65b; 22.1 ± 2.62a); plasma membrane integrity (47.5 ± 4.65a; 62.9 ± 5.41b; 39.1 ± 4.32a); percentage of leukocytes (35.2 ± 2.36a; 15.1 ± 2.55b; 36.1 ± 4.04a); CFU (119 980 × 103 ± 19 528.0 × 103a; 5375 × 103 ± 2453.7 × 103b; 65 850 × 103 ± 19 701.0 × 103ab) on fresh semen; and NO content (0.645 ± 0.172a, 0.117 ± 0.023b, 0.364 ± 0.110ab) on seminal plasma. The results demonstrate that local treatment after a week leads to an improvement in sperm quality; however, this was not maintained after 1 month of therapy, since the seminal parameters at this time are similar to pretreatment, which can be justified by recurrent disease.

Effects of polychlorinated biphenyls 28, 30 and 118 on bovine spermatozoa in vitro.

Decline of semen quality due to endocrine-disrupting chemicals is of concern globally. Among endocrine disrupting chemicals (EDC), Polychlorinated biphenyls (PCB) are associated with reduced semen quality in various epidemiological studies. In this study, we evaluated the direct effects of selected PCBs (28, 30 and 118) on fresh spermatozoa of Simmetial bulls aged 2-4 years were evaluated in vitro by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and computer assisted semen analysis (CASA) (SCA; Microptics) analysis. IC50 values were found as 8.45, 5.45 and 9.55 ng/ml for PCB 28, 30 and 118, respectively. Total motility, progressive motility and viability decreased dependent on dose and duration of exposure (0, 2, 4 h). Total motility at IC50 doses decreased the most in PCB 28 (72.24%) followed by 30 (60.75%) and 118 (64.77%) at 2nd hour following exposure. Motility results were found to be in accordance with the vitality and morphology data where total abnormalities (especially reacted acrosome rate) were found to have increased.

Habitual alcohol consumption associated with reduced semen quality and changes in reproductive hormones; a cross-sectional study among 1221 young Danish men

ObjectiveStudy associations between three measures of alcohol consumption (recent, typical/habitual, binging), semen quality and serum reproductive hormones.DesignCross-sectional population based study.Setting and participants1221 young Danish men, aged 18–28 years were recruited...

Addition of superoxide dismutase mimics during cooling process prevents oxidative stress and improves semen quality parameters in frozen/thawed ram spermatozoa

High levels of reactive oxygen species (ROS), which may be related to reduced semen quality, are detected during semen cryopreservation in some species. The objectives of this study were to measure the oxidative stress during ram semen cryopreservation and to evaluate the effect of adding 2 antioxidant mimics of superoxide dismutase (Tempo and Tempol) during the cooling process on sperm motility, viability, acrosomal integrity, capacitation status, ROS levels, and lipid peroxidation in frozen and/or thawed ram spermatozoa. Measuring of ROS levels during the cooling process at 35, 25, 15, and 5 °C and after freezing and/or thawing showed a directly proportional increase (P < 0.05) when temperatures were lowering. Adding antioxidants at 10 °C confered a higher motility and sperm viability after cryopreservation in comparison with adding at 35 °C or at 35 °C/5 °C. After freezing and/or thawing, sperm motility was significantly higher (P < 0.05) in Tempo and Tempol 1 mM than that in control group. Percentage of capacitated spermatozoa was lower (P < 0.05) in Tempo and Tempol 1 mM in comparison with that in control group. In addition, ROS levels and lipid peroxidation in group Tempo 1 mM were lower (P < 0.05) than those in control group. These results demonstrate that ram spermatozoa are exposed to oxidative stress during the cooling process, specifically when maintained at 5 °C and that lipid peroxidation induced by high levels of ROS decreases sperm motility and induces premature sperm capacitation. In contrast, the addition of Tempo or Tempol at 0.5 to 1 mM during the cooling process (10 °C) protects ram spermatozoa from oxidative stress.

Genetic Variation of Choline Dehydrogenase Gene in Idiopathic Male Infertility

Infertility can be caused by an unexplained reduction in semen quality in males who present asnormal on physical examination and endocrine testing. There is some evidence that aberrantmetabolism of micronutrients such as choline may play a causative role in male factorinfertility. Choline is a crucial factor in the regulation of sperm membrane structure andmotility, and this nutrient plays an important role in the maturing and fertilizing capacity ofspermatozoa. In the present study, we explored the contribution of the choline dehydrogenasegene polymorphism located in the codon 78 (CHDH +432G>T), one of the basic enzymes ofcholine metabolism, to idiopathic male infertility. In this study, 50 infertile men and 50 fertilemen of the Guilan population were selected. Genomic DNA was extracted from peripheralblood. Genotypes were determined by polymerase chain reaction (PCR) and restrictionfragment length polymorphism (RFLP). Statistical analysis was performed using MedCalcsoftware (v12.1.4.0). A significant difference was observed between patients and healthysubjects in the distribution of G and T alleles. The prevalence of genotype frequencies ofCHDH +432 GG, GT, and TT were 28%, 50%, and 22%, respectively, in patients, while inhealthy subjects they were 52%, 36%, and 12%, respectively. In other words, there was asignificant difference in the genotype distribution of CHDH +432G>T in patients comparedwith controls (Ρ<0.05). This finding suggests a possible influence of this gene polymorphism onidiopathic male infertility.

Effect of alternate day collection on semen quality of Asian elephants (Elephas maximus) with poor initial fresh semen quality

In captivity, male Asian elephants often yield poor quality semen after transrectal manually assisted semen collection; however, the reasons for the disappointing semen quality are not clear. Here we test the hypothesis that accumulation of senescent spermatozoa is a contributory factor, and that semen quality can therefore be improved by more frequent ejaculation. To this end we investigated the effect of collecting semen five times on alternate days, after a long period of sexual rest, on semen quality in Asian elephants known to deliver poor semen during infrequent single collections. All eight bulls initially displayed a high incidence of detached sperm heads and low percentages of motile (close to 0%) spermatozoa. After semen collection on alternate days, the percentages of detached sperm heads, and head and mid-piece abnormalities, were reduced significantly (p<0.05). In particular, one bull showed markedly improved sperm motility (increased from 0% to 60%) and membrane integrity (increased from 5% to 75%). In addition, advancing age significantly (p<0.01) correlated with lower percentages of sperm with intact membranes and a higher frequency of detached sperm heads. In contrast to sperm accumulation problems in other species, a small ampullary diameter correlated significantly (p<0.05) with reduced semen quality.

Adherence to reporting guidelines in observational studies concerning exposure to persistent organic pollutants and effects on semen parameters

Are studies on semen quality in men exposed to persistent pesticides reported according to the 'strengthening the reporting of observational studies in epidemiology' (STROBE) recommendations and the guidelines for the appraisal of semen quality studies (SEMQUA)? Most studies of the impact of pesticides on semen quality do not follow the STROBE and SEMQUA guidelines, thus adherence is low, especially in methodological aspects. Much of the controversy about reduced semen quality in recent decades arises from a lack of standardization in the methodology applied, despite the existence of several validated instruments for evaluating the quality of reporting. Indeed, SEMQUA was purpose-designed for the particular characteristics of semen quality studies. A structured literature search identified eligible articles reporting on persistent pesticides and human semen quality, published in English before 1 September 2012. Opinion articles and reviews were excluded. We assessed the adherence to reporting guidelines of the articles, using and comparing the STROBE statement and the SEMQUA guidelines, in both cases with indicators relevant to observational studies of semen quality. A comprehensive bibliographic search in various electronic literature databases using the key words 'sperm' and 'pesticide' obtained 1179 papers, of which 46 were valid for our purposes. The papers examined occupational (26) and environmental exposure (20). Two of the present authors independently piloted the data extraction form for this review. The articles were then evaluated by two researchers using the STROBE and SEMQUA checklists. Although no significant differences were found between the overall degree of compliance with STROBE and SEMQUA (47.0 ± 18.5% versus 43.1 ± 11.6%), there were significant differences when only methodological aspects were considered (48.4 ± 21.0% versus 39.5 ± 17.4%; P < 0.001). We observed an increase over time in the degree of compliance, for SEMQUA (r = 0.61 and P < 0.001) and STROBE (r = 0.45 and P < 0.01). The papers that reported a negative effect of exposure to persistent pesticides on sperm concentration presented a lower level of compliance to SEMQUA (42.1 ± 18.3% versus 57.6 ± 14.2%; P < 0.01) and STROBE (40.2 ± 10.3% versus 49.5 ± 11.6%; P < 0.05) than those which recorded no such influence. The year of publication and the observed effect on sperm concentration were the only candidate variables included in the model of stepwise multiple regression model for the 'degree of compliance' variables of SEMQUA and STROBE. Other characteristics of reporting quality, such as legibility, were not evaluated. The low degree of compliance observed is consistent with that observed in other studies of reproductive medicine and highlights the need to improve the design of studies of semen quality. SEMQUA proved to be a more specific tool than STROBE for the field of semen quality. Editors, reviewers and authors should be aware of SEMQUA and apply it when assessing papers on semen quality. No research funding was received and none of the authors have any conflict of interests.

Soluble human leukocyte antigen-G in seminal plasma is associated with HLA-G genotype: possible implications for fertility success.

We have previously shown that human seminal plasma contains immunomodulatory soluble HLA-G (sHLA-G). We investigated whether sHLA-G levels in seminal plasma are associated with a specific 14 base pair (bp) insertion/deletion (ins/del) polymorphism in the 3'-untranslated region of the HLA-G gene and/or with the outcome of assisted reproduction treatments (ART) in couples attending a fertility clinic. In a total of 54 unselected couples, sHLA-G levels were measured in seminal plasma samples and blood samples, HLA-G genotyping was performed, and clinical data were collected. The concentration of sHLA-G in seminal plasma samples was significantly associated with the HLA-G 14 bp ins/del genotype of the men; the del14 bp/del14 bp genotype showed the highest level of sHLA-G, and the ins14 bp/ins14 bp genotype showed the lowest level (P = 0.003). We observed a trend for higher seminal plasma levels of sHLA-G/total protein and total sHLA-G in cases with reduced semen quality, where the female partner became pregnant after ART, compared with those couples in which no pregnancy was achieved. These first results are in accordance with a possible role of seminal sHLA-G as an immunomodulatory factor in the female reproductive tract before and at the time of conception.

Disturbances of sperm maturation and minipuberty: is there a connection?

Male reproductive function in the general population raises an increased attention due to reports indicating declining sperm counts, increased occurrence of testicular cancer, cryptorchidism, and hypospadias. It is also hypothesized that prolonged exposure of the developing male, during both fetal and postnatal life, to exogenous estrogens could reduce Sertoli cell number and thus reduce sperm output (and sperm counts) in adult life. Fact is that infertility, which is defined as the inability to conceive after 1 year of unprotected intercourse, has a global prevalence of 9%. A male contributory factor is involved in approximately half of these cases, but most of the causes of reduced semen quality and other disturbances of male reproductive function are unknown. In the most affected men (azoospermic men) 15–20% had a prior history of cryptorchidism. The association between the cryptorchidism and infertility is one of the most studied potential causes of infertility. There are numerous studies that accentuate the importance of minipuberty for future fertility. Is it possible that a normal minipuberty ensures normal fertility despite malpositioned testes? And to move away from cryptorchidism, could impaired minipuberty be responsible for fertility problems in men who were born with both testes in their scrotal sacs?

Maternal pre-pregnancy body mass index and pubertal development among sons

Maternal overweight and obesity in pregnancy has been associated with earlier age of menarche in daughters as well as reduced semen quality in sons. We aimed at investigating pubertal development in sons born by mothers with a high body mass index (BMI). The study included 2522 sons of mothers that during pregnancy in 1984-1987 were enrolled in a mother-child cohort and gave information on their pre-pregnancy height and weight from which we calculated their BMI. Information on sons' pubertal development, assessed by age when starting regular shaving, voice break, acne and first nocturnal emission, was obtained from web-based questionnaires in 2005, when sons were 18-21 years old. Multiple linear regression analyses showed that sons of obese mothers on average started to shave regularly 8.3 (95% confidence interval: 2.5-14.0) months earlier than sons of normal weight mothers. For the three other indicators of pubertal development, results also indicated earlier pubertal development among sons of obese mothers. After excluding sons of underweight mothers in a subanalysis, we observed an inverse trend between maternal pre-pregnancy BMI and age at regular shaving, acne and first nocturnal emission. In conclusion, maternal pre-pregnant obesity may be related to earlier timing of pubertal milestones among sons. More research, preferably based on prospectively collected information about pubertal development, is needed to draw firm conclusions.

Male Infertility Workup Needs Additional Testing of Expressed Prostatic Secretion and/or Post-Massage Urine

The male factor accounts for almost 50% of infertility cases. Inflammation may reduce semen quality via several pathways, including oxidative stress (OxS). As male infertility routinely is assessed using semen analysis only, the possible presence of non-leukocytospermic asymptomatic inflammatory prostatitis may be overlooked. We compared local and systemic OxS levels in male partners of infertile couples with different inflammation patterns in their genital tract and/or oligospermia.Subjects (n=143) were grouped according to inflammation in their semen, expressed prostatic secretion (EPS), and/or post-massage urine (post-M). Systemic (8-isoprostanes in urine) and local (diene conjugates and total antioxidant capacity in seminal plasma) OxS was measuredThe levels of OxS markers were significantly elevated in both severe inflammation groups – leukocytospermic men and subjects whose inflammation was limited only to EPS and/or post-M. Comparison between oligospermic and non-oligospermic men with genital tract inflammation, and oligozoospermic men with or without inflammation in the genital tract indicated that inflammation but not oligospermia status had significant impact on the measured OxS markers.Hence, a high leukocyte count in prostate-specific materials (EPS, post-M), even in absence of clear leukocytopsermia, is an important source of local and systemic OxS that may be associated with male infertility and affect general health. We suggest including the tests for detection of inflammation of the prostate into the workup of infertile men as was suggested in the WHO 1993 recommendation.

Vanadium inhalation induces actin changes in mice testicular cells

Infertility is becoming a health problem, which has increased mainly in megacities, and several studies have shown its association with environmental pollution. Air pollution has been linked to alterations in sperm parameters, both in humans and animal models. In male humans, it has been associated with reduced semen quality and DNA alterations. Vanadium is a transition element that has increased in recent decades as a component of air suspended matter and has been associated with reprotoxic effects in animal models. Few are the mechanisms described by which the vanadium produces these effects, and cytoskeleton interaction is a possibility. We reported immunohistochemical changes in actin testicular cytoskeleton in a vanadium inhalation experimental mice model. Our findings show that exposure to vanadium pentoxide (0.02 M) results in actin decrease in testicular cells from 3-12 weeks exposure time; this effect was statistically significant and exposure time dependent. Actin cytoskeleton damage is a mechanism that could explain vanadium reprotoxic effects and its association with impaired fertility.

Detection of persistent organic pollutants binding modes with androgen receptor ligand binding domain by docking and molecular dynamics

BackgroundPersistent organic pollutants (POPs) are persistent in the environment after release from industrial compounds, combustion productions or pesticides. The exposure of POPs has been related to various reproductive disturbances, such as reduced semen quality, testicular cancer, and imbalanced sex ratio. Among POPs, dichlorodiphenyldichloroethylene (4,4’-DDE) and polychlorinated biphenyls (PCBs) are the most widespread and well-studied compounds. Recent studies have revealed that 4,4’-DDE is an antagonist of androgen receptor (AR). However, the mechanism of the inhibition remains elusive. CB-153 is the most common congener of PCBs, while the action of CB-153 on AR is still under debate.ResultsMolecular docking and molecular dynamics (MD) approaches have been employed to study binding modes and inhibition mechanism of 4,4’-DDE and CB-153 against AR ligand binding domain (LBD). Several potential binding sites have been detected and analyzed. One possible binding site is the same binding site of AR natural ligand androgen 5α-dihydrotestosterone (DHT). Another one is on the ligand-dependent transcriptional activation function (AF2) region, which is crucial for the co-activators recruitment. Besides, a novel possible binding site was observed for POPs with low binding free energy with the receptor. Detailed interactions between ligands and the receptor have been represented. The disrupting mechanism of POPs against AR has also been discussed.ConclusionsPOPs disrupt the function of AR through binding to three possible biding sites on AR/LBD. One of them shares the same binding site of natural ligand of AR. Another one is on AF2 region. The third one is in a cleft near N-terminal of the receptor. Significantly, values of binding free energy of POPs with AR/LBD are comparable to that of natural ligand androgen DHT.

Twenty-four hours abstinence and the quality of sperm parameters

Patients with abnormal basic parameters and mainly low concentration can be expected to have improved parameters on the second consecutive day. As the number of abnormal basic parameters increases, the more significant improvement can be expected. On the other hand, patients with normal or few abnormal basic semen parameters show a decrease after 24 h. Furthermore, the magnitude of change to both directions in TMC and TNMC values in these patients emphasises these conclusions. Based on the type and mainly the combined number of abnormal basic semen parameters, insemination strategy can be tailored to male fertility patients. Those with abnormal concentration or multiple abnormal semen parameters may benefit from 2 consecutive day intercourses or inseminations or a short period of abstinence due to a significant improvement in the semen parameters on second day insemination. In those with normal basic semen parameters, a reduction in semen quality is expected after 24 h, and a single-timed insemination and longer abstinence can be recommended.

Association of Sleep Disturbances With Reduced Semen Quality: A Cross-sectional Study Among 953 Healthy Young Danish Men

Several studies have found an association between sleep duration and morbidity and mortality, but no previous studies have examined the association between sleep disturbances and semen quality. We conducted a cross-sectional study among 953 young Danish men from the general population who were recruited in Copenhagen at the time of determination of fitness for military service between January 2008 and June 2011. All of the men delivered a semen sample, had a blood sample drawn, underwent a physical examination, and answered a questionnaire including information about sleep disturbances. Sleep disturbances were assessed on the basis of a modified 4-item version of the Karolinska Sleep Questionnaire, which includes questions on sleep patterns during the past 4 weeks. Sleep disturbances showed an inverse U-shaped association with sperm concentration, total sperm count, percent motile and percent morphologically normal spermatozoa, and testis size. Men with a high level of sleep disturbance (score >50) had a 29% (95% confidence interval: 2, 48) lower adjusted sperm concentration and 1.6 (95% confidence interval: 0.3, 3.0) percentage points' fewer morphologically normal spermatozoa than men with a sleep score of 11-20. This appears to be the first study to find associations between sleep disturbances and semen quality. In future studies, investigators should attempt to elucidate mechanistic explanations and prospectively assess whether semen quality improves after interventions restoring a normal sleeping pattern.

High dietary intake of saturated fat is associated with reduced semen quality among 701 young Danish men from the general population

Saturated fat intake has been associated with both cardiovascular disease and cancer risk, and a newly published study found an association between saturated fat intake and a lower sperm concentration in infertile men. The objective was to examine the association between dietary fat intake and semen quality among 701 young Danish men from the general population. In this cross-sectional study, men were recruited when they were examined to determine their fitness for military service from 2008 to 2010. They delivered a semen sample, underwent a physical examination, and answered a questionnaire comprising a quantitative food-frequency questionnaire to assess food and nutrient intakes. Multiple linear regression analyses were performed with semen variables as outcomes and dietary fat intakes as exposure variables, adjusted for confounders. A lower sperm concentration and total sperm count in men with a high intake of saturated fat was found. A significant dose-response association was found, and men in the highest quartile of saturated fat intake had a 38% (95% CI: 0.1%, 61%) lower sperm concentration and a 41% (95% CI: 4%, 64%) lower total sperm count than did men in the lowest quartile. No association between semen quality and intake of other types of fat was found. Our findings are of potentially great public interest, because changes in diet over the past decades may be part of the explanation for the recently reported high frequency of subnormal human sperm counts. A reduction in saturated fat intake may be beneficial for both general and reproductive health.

The usefulness of Real Time Morphology software in semen assessment of teratozoospermic boars

The aim of the present study was to compare two different techniques of sperm cell morphology evaluation in teratozoospermic boars: computer assisted semen morphology analysis and conventional assessment of stained semen smears. The semen samples were collected manually from 30 boars with reduced semen quality. In all samples the percentage of morphologically normal spermatozoa was below 70%. Computer assisted semen morphology assessment was performed using the Real Time Morphology (RTM) software (IVOS ver. 12.2, Hamilton Thorne Bioscience). The assessment was made by phase contrast optics, with the magnification of 20 x 3.8 and without staining. Conventional morphology assessment was performed by bright field microscopy with 1,000 x magnification after staining with Giemsa. At least 200 spermatozoa were evaluated per slide in both methods. The Bland-Altman plot indicated a general agreement between both methods of sperm morphology evaluation. The plots revealed the widest limits of agreement (mean ± 1.96 SD) for the percentage of midpiece anomalies (from −16 to 13.2), and the narrowest for the percentage of looped tail (from −1.49 to 1.09). The Bland Altman plot indicates general agreement between RTM and Giemsa staining in the percentage of major and minor defects. However, it was not possible to evaluate acrosomes using RTM. Otherwise, RTM proved to be a valuable tool in sperm morphology assessment, with accuracy equal to typical conventional methods.

The association between sperm sex chromosome disomy and semen concentration, motility and morphology.

Is there an association between sex chromosome disomy and semen concentration, motility and morphology? Higher rates of XY disomy were associated with a significant increase in abnormal semen parameters, particularly low semen concentration. Although some prior studies have shown associations between sperm chromosomal abnormalities and reduced semen quality, results of others are inconsistent. Definitive findings have been limited by small sample sizes and lack of adjustment for potential confounders. Cross-sectional study of men from subfertile couples presenting at the Massachusetts General Hospital Fertility Clinic from January 2000 to May 2003. With a sample of 192 men, multiprobe fluorescence in situ hybridization for chromosomes X, Y and 18 was used to determine XX, YY, XY and total sex chromosome disomy in sperm nuclei. Sperm concentration and motility were measured using computer-assisted sperm analysis; morphology was scored using strict criteria. Logistic regression models were used to evaluate the odds of abnormal semen parameters [as defined by World Health Organization (WHO)] as a function of sperm sex chromosome disomy. The median percentage disomy was 0.3 for XX and YY, 0.9 for XY and 1.6 for total sex chromosome disomy. Men who had abnormalities in all three semen parameters had significantly higher median rates of XX, XY and total sex chromosome disomy than controls with normal semen parameters (0.43 versus 0.25%, 1.36 versus 0.87% and 2.37 versus 1.52%, respectively, all P< 0.05). In logistic regression models, each 0.1% increase in XY disomy was associated with a 7% increase (odds ratio: 1.07, 95% confidence interval: 1.02-1.13) in the odds of having below normal semen concentration (<20 million/ml) after adjustment for age, smoking status and abstinence time. Increases in XX, YY and total sex chromosome disomy were not associated with an increase in the odds of a man having abnormal semen parameters. In addition, autosomal chromosome disomy (1818) was not associated with abnormal semen parameters. A potential limitation of this study, as well as those currently in the published literature, is that it is cross-sectional. Cross-sectional analyses by nature do not lend themselves to inference about directionality for any observed associations; therefore, we cannot determine which variable is the cause and which one is the effect. Additionally, the use of WHO cutoff criteria for dichotomizing semen parameters may not fully define fertility status; however, in this study, fertility status was not an outcome we were attempting to assess. This is the largest study to date seeking to understand the association between sperm sex chromosome disomy and semen parameters, and the first to use multivariate modeling to understand this relationship. The findings are similar to those in the published literature and highlight the need for mechanistic studies to better characterize the interrelationships between sex chromosome disomy and standard indices of sperm health. This work was supported by grants from NIOSH (T42 OH008416) and NIEHS (R01 ES009718, P30 ES000002 and R01 ES017457). The authors declare no competing interests. At the time this work was conducted and the initial manuscript written, MEM was affiliated with the Environmental Health Department at the Harvard School of Public Health. Currently, MEM is employed by Millennium: The Takeda Oncology Company. N/A.

Effect of smoking on the functional aspects of sperm and seminal plasma protein profiles in patients with varicocele

What are the effects of smoking on the functional aspects of the sperm, the levels of lipid peroxidation and the protein profile of seminal plasma in patients with varicocele? In men with varicocele, smoking is associated with altered semen quality, decreased sperm functional integrity and seminal oxidative stress. Alterations in seminal plasma protein profiles are also present and may explain the altered semen phenotype. Varicocele is a major cause of male infertility. It reduces testicular blood renewal with a consequent accumulation of toxic substances. Thus, it can potentiate the toxic effects of environmental exposure to genotoxic substances such as those found in cigarette smoke. A cross-sectional study was performed in 110 patients presenting with variococele to the Human Reproduction Section of the Sao Paulo Federal University (2006-2010). The patients were divided into a control group of non-smokers, a moderate smokers group and a heavy smokers group. Semen parameters were analysed by standard methods. Sperm DNA integrity and mitochondrial activity were assessed by Comet assays and by 3,3'-diaminobenzidine deposition, respectively. The level of lipid peroxidation in semen was determined by malondialdehyde quantification. Proteomic studies were performed by 2D-electrophoresis and mass spectrometry. Both groups of smokers showed reduced semen quality in comparison with the control group. In the groups of smokers, sperm DNA integrity and mitochondrial activity were also decreased and lipid peroxidation levels were increased. Proteomic analyses revealed 20 proteins differentially expressed between the study groups. A study including smokers without varicocele is still warranted as these results apply only to smokers who present varicocele. Patients with varicocele who are exposed to tobacco smoking present more important alterations to semen quality and sperm functional integrity and show changes in the seminal plasma proteome. This suggests testicular, and possibly systemic, adverse effects of smoking. Funding for the study was provided by Fundação de Amparo à Pesquisa do Estado de São Paulo (Fapesp) (2007/59423-7) and by the Division of Urology, Human Reproduction Section at the São Paulo Federal University.