interleukin-8 and Infertility--Male

Male infertility is a serious diagnostic problem and in many cases the exact cause of failure to reproduce remains unknown. New diagnostic methods are being evaluated in search of more precise diagnosis and possibility of casual treatment. Measuring the level of cytokines, both in seminal plasma and serum, does not only expand the diagnostic options, but also, through the growing knowledge of immune processes, can give rise to new therapeutic methods of improving the quality of semen and increasing the chance to reproduce. The article reviews the role of proinflammatory cytokines in its pathogenesis.

Topics: Antibody Formation; Antigens; Autoimmunity; Cytokines; Enzyme-Linked Immunosorbent Assay; Humans; Infertility, Male; Interleukin-1; Interleukin-11; Interleukin-12; Interleukin-2; Interleukin-6; Interleukin-8; Male; Semen; Spermatozoa

The effects of 24 weeks of high-intensity interval training (HIIT) on markers of male reproductive function in infertile patients were studied. Infertile men (n = 441) were randomized to exercise (EX, n = 221) or non-exercise (NON-EX, n = 220) group. Patients in the EX group performed an interval training (1:1 work:rest ratio) 3 times per week at 75-95% of maximal oxygen consumption, for 24 weeks (VO

Topics: Adult; Antioxidants; Correlation of Data; Cytokines; Dinoprost; Exercise Therapy; Female; High-Intensity Interval Training; Humans; Infertility, Male; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Oxidative Stress; Oxygen Consumption; Pregnancy; Reactive Oxygen Species; Semen; Spermatozoa; Tumor Necrosis Factor-alpha

The aim of this study is to evaluate the effect of massive weight loss on the seminal parameters at 6 months from bariatric surgery.. Two-armed prospective study performed in 31 morbidly obese men, undergoing laparoscopic roux-en-Y-gastric bypass (n = 23) or non-operated (n = 8), assessing sex hormones, conventional (sperm motility, morphology, number, semen volume), and non-conventional (DNA fragmentation and seminal interleukin-8), semen parameters, at baseline and after 6 months from surgery or patients' recruitment.. In operated patients only, a statistically significant improvement in the sex hormones was confirmed. Similarly, a positive trend in the progressive/total sperm motility and number was observed, though only the increase in semen volume and viability was statistically significant (Δ = 0.6 ml and 10%, P < 0.05, respectively). A decrease in the seminal interleukin-8 levels and in the sperm DNA fragmentation was also present after bariatric surgery, whereas these parameters even increased in non-operated subjects. Age-adjusted multivariate analysis showed that the BMI variations significantly correlated with the changes in the sperm morphology (β = -0.675, P = 0.025), sperm number (β = 0.891, P = 0.000), and semen volume (r = 0.618, P = 0.015).. The massive weight loss obtained with bariatric surgery was associated with an improvement in some semen parameters. The correlations found between weight loss and semen parameter variations after surgery suggest that these might occur early downstream of the testis and more slowly than the changes in the sex hormones.

Topics: Adult; Bariatric Surgery; Body Mass Index; Follow-Up Studies; Humans; Infertility, Male; Interleukin-8; Laparoscopy; Longitudinal Studies; Male; Middle Aged; Obesity, Morbid; Pilot Projects; Semen; Semen Analysis; Treatment Outcome; Weight Loss

Interleukin (IL)-38 and IL-41 are novel cytokines, but their role in male infertility (MI) is unknown. The purpose of this study was to measure the levels of serum IL-38 and IL-41 in patients with MI and correlate these levels with semen indexes.. Eighty-two patients with MI and 45 healthy controls (HC) were recruited for this study. Semen parameters were detected using computer-aided sperm analysis, Papanicolaou staining, ELISA, flow cytometry, peroxidase staining and enzyme methods. Serum IL-38 and IL-41 levels were determined by ELISA.. Serum IL-38 levels were decreased (P < 0.01) in patients with MI compared with HC. Serum IL-41 levels were significantly higher in patients with MI than in HC (P < 0.0001). In patients with MI, serum IL-38 levels were positively correlated with semen white blood cell counts (r = 0.29, P = 0.009), and there was a positive correlation between semen white blood cell counts and sperm concentration (r = 0.28, P = 0.0100) and seminal plasma elastase (r = 0.67, P < 0.0001). Receiver operating characteristic curve analysis showed that the area under the curve of IL-38 for diagnosing MI was 0.5637 (P > 0.05), and the area under the curve of IL-41 for diagnosing MI was 0.7646 (P < 0.0001).. Serum IL-38 levels were significantly lower, and serum IL-41 levels were higher in patients with MI. These results suggest that IL-38 and IL-41 may be novel biomarkers for the diagnosis of MI.

Topics: Biomarkers; Humans; Infertility, Male; Interleukin-8; Interleukins; Male; Semen; Sperm Count

Urogenital inflammation is a known cause of male infertility. Increased levels of inflammatory cytokines, leukocyte counts and oxidative stress are highly detrimental for sperm quality thus compromising male fertility. Although cytokines affect sperm by recruiting and activating leukocytes consequently inducing tissue inflammation and oxidative stress, scarce to absent data have been reported about the putative direct effects of inflammatory cytokines on spermatozoa. Herein, we analyzed whether IFNγ, IL-17A, IL-1β, and IL-8 can alter human sperm motility and viability per se. Fractions of viable and motile spermatozoa from normospermic healthy donors were in vitro incubated with recombinant human IFNγ, IL-17A, IL-1β or IL-8 and sperm ROS production, motility, viability and apoptosis were analyzed. Sperm exposed to different concentrations of IFNγ, IL-17A and IL-1β, or a combination of them, for either 1 or 3 h showed significantly increased levels of mitochondrial ROS production and reduced motility and viability with respect to sperm incubated with vehicle. Moreover, the exposure to IFNγ, IL-17A and IL-1β resulted in significantly higher levels of early and/or late apoptotic and/or necrotic spermatozoa. Interestingly, no significant differences in sperm motility, viability and apoptosis were observed in sperm incubated with the concentrations of IL-8 analyzed, for either 1 or 3 h, with respect to sperm incubated with vehicle. In conclusion, our results indicate that IFNγ, IL-17A and IL-1β per se impair sperm motility and decreases viability by triggering increased mitochondrial ROS production and inducing sperm apoptosis. Our results suggest that screening inflammatory cytokines in semen would be an additional helpful tool for the diagnostic workup of male infertility.

Topics: Apoptosis; Cytokines; Humans; Infertility, Male; Inflammation; Interferon-gamma; Interleukin-17; Interleukin-1beta; Interleukin-8; Male; Reactive Oxygen Species; Sperm Motility; Spermatozoa

Topics: Adult; Catalase; Cell Nucleus; DNA Damage; DNA Fragmentation; DNA, Mitochondrial; Glutathione; Humans; Infertility, Male; Interleukin-6; Interleukin-8; Leukocytes; Male; Malondialdehyde; Oxidative Stress; Semen; Spermatozoa; Superoxide Dismutase

Advanced glycation end products (AGEs) affect the follicular microenvironment. The close relationship between AGEs, proinflammatory cytokine production and activation of the unfolded protein response (UPR), which involves activating transcription factor 4 (ATF4), is crucial for regulation of various cellular functions. We examined whether accumulation of AGEs in follicles was associated with proinflammatory cytokine production and activation of the UPR in granulosa cells and decreased oocyte developmental competence. Concentrations of AGEs, soluble receptor for AGE (sRAGE), interleukin (IL)-6 and IL-8 in follicular fluid (FF) were examined by ELISAs in 50 follicles. mRNA expression of ATF4, IL-6 and IL-8 in cumulus cells (CCs) were examined by quantitative RT-PCR in 77 samples. Cultured human granulosa-lutein cells (GLCs) were treated with AGE-bovine serum albumin (BSA) alone or following transfection of ATF4-targeting small interfering RNA. The AGE concentration and the AGE/sRAGE ratio in FF were significantly higher in follicles containing oocytes that developed into poor-morphology embryos (group I) than those with good-morphology embryos (group II). When compared with sibling follicles from the same patients, the AGE/sRAGE and concentrations of IL-6 and IL-8 in FF, as well as ATF4, IL-6 and IL-8 mRNA expression in CCs, were significantly higher in group I follicles than group II. AGE treatment increased mRNA expression of ATF4, IL-6 and IL-8 in cultured GLCs. Knockdown of ATF4 abrogated the stimulatory effects of AGE on mRNA expression and protein secretion of IL-6 and IL-8. Our findings support the idea that accumulation of AGEs in follicles reduces oocyte competence by triggering inflammation via activation of ATF4 in the follicular microenvironment.

Topics: Activating Transcription Factor 4; Adult; Cells, Cultured; Cumulus Cells; Female; Follicular Fluid; Glycation End Products, Advanced; Granulosa Cells; Humans; Infertility, Female; Infertility, Male; Interleukin-6; Interleukin-8; Luteal Cells; Male; Middle Aged; Oocytes; Oogenesis; Receptor for Advanced Glycation End Products; Unfolded Protein Response

Is there any association between mixed antiglobulin reaction (MAR) test positivity and clinical features or genital tract ultrasound (US) parameter values in males of infertile and fertile couples?. In males of infertile and fertile couples MAR test positivity was associated with clinical and US features suggestive of chronic epididymal inflammation.. MAR test positivity has been more often reported in males of infertile couples than in fertile men. A positive MAR test has been detected in men with a history of testicular or post-testicular damage. No previous study has reported US alterations related to MAR test positivity. This is the first study that has systematically evaluated associations between a positive MAR test and clinical, seminal and US characteristics of the entire male genital tract.. This cross-sectional analysis included 109 fertile men and 699 consecutive subjects seeking medical care for couple infertility from September 2012 to September 2017.. All subjects underwent, in our outpatient clinic, a complete physical, endocrine, scrotal and transrectal US evaluation and semen analysis (including sIL-8) on the same day. Of the 699 males of infertile couples, 181 (age 38.6 ± 6.6 years) had an assessable MAR test, whereas the test was assessable in all 109 fertile men (age 36.6 ± 5.2 years). The associations among MAR test positivity and the other studied parameters were investigated on a caseload of 290 men (patients + fertile men) and in the two cohorts of males of infertile and fertile couples.. Of the 181 men of infertile couples studied, 20 (11%) had a positive MAR test, including 12 (6.6%) who had a MAR test ≥ 50%, which is considered as a pathological threshold according to the WHO. Of the 109 fertile men, four (3.7%) had a positive MAR test, of which one (0.9%) had a MAR test ≥ 50%. MAR test positivity was therefore found more often in men of infertile couples (P < 0.05). In the entire caseload (n = 290) of males of both infertile and fertile couples, no correlations between MAR test positivity and seminal characteristics were observed. A positive MAR test was associated with epididymal US abnormalities, particularly with the mean size of the epididymal body and tail (both P < 0.0001), and in infertile men, a positive MAR test was also associated with an abnormal epididymal echotexture. In addition, subjects with a positive MAR test more frequently showed a history of epididymitis and high sIL-8 levels. Considering endocrine parameters, only a positive correlation between MAR test positivity and LH levels was observed, even after adjusting for age and life-style factors (adj. r = 0.232, P < 0.0001), while no associations with testosterone and FSH levels were found.. Antisperm antibodies (ASA) were detected in this study by using the SpermMAR test IgG, but other tests are available. In addition, for technical reasons, the MAR test is not assessable in subjects with severe oligo-astheno-zoospermia and, therefore, this test may lead to an intrinsic selection bias. Finally, owing to the cross-sectional nature of the study, neither a causality hypothesis nor mechanistic models can be inferred.. First, our results indicate that MAR test positivity is associated with clinical and US signs suggestive of chronic epididymal inflammation and not testicular damage. Hence, when investigating a subject with a positive MAR test, the epididymis and not just the testis should be evaluated. Furthermore, MAR test positivity was more often detected in males of infertile couples than in fertile men, but it was not associated with conventional semen parameter values. Our data support a role of ASA in couple infertility, regardless of the conventional sperm analysis. How ASA affects couple fertility needs to be addressed by further studies.. Grants were received from the Ministry of University and Scientific Research (SIR project to F.L., protocol number: RBSI14LFMQ). There are no conflicts of interest.. N/A.

Topics: Adult; Autoantibodies; Cross-Sectional Studies; Epididymis; Female; Fertility; Humans; Immunoglobulin G; Immunologic Techniques; Infertility, Male; Interleukin-8; Luteinizing Hormone; Male; Predictive Value of Tests; Pregnancy; Semen; Semen Analysis; Spermatozoa; Testis; Ultrasonography, Doppler, Color

Previous studies have given conflicting results about the effect of generally infection and Chlamydia trachomatis on seminal ILs and semen parameters. The aim of this study was to investigate the relationship between semen quality and the level of seminal interleukins (ILs) in infertile couples with C. trachomatis. Blood, first void urine (FVU) and semen were obtained from 250 infertile men who had failed to conceive after 12 months of trying. Serological analysis for specific IgA, IgM and IgG antibodies to C. trachomatis in serum, the presence of C. trachomatis in FVU and semen sample and semen analysis were carried out. The main results are as follows: (i) elevated IL-6 and IL-8 are observed in C. trachomatis-positive men, but this is not significant and it varies by diagnostic method; and (ii) IL-6 and IL-8 levels were correlated with each other and the concentration of leucocytes, but IL-8 was correlated with semen volume and patient's age. This study showed that men with such an infection in FVU samples (PCR positive) had only lower semen volume compared with men without infection.

Topics: Adult; Antibodies, Bacterial; Biomarkers; Chlamydia Infections; Chlamydia trachomatis; Humans; Infertility, Male; Inflammation; Interleukin-6; Interleukin-8; Iran; Male; Middle Aged; Polymerase Chain Reaction; Semen; Semen Analysis; Young Adult

Is thyroid hormones (TH) evaluation of clinical value in the work-up of males of infertile couples?. Our results suggest that TH evaluation is not mandatory in the work-up of male infertility.. A few previous studies performed on a limited series of subjects reported a negative impact of hyper- and hypo-thyroidism on semen volume, sperm concentration, progressive motility and normal morphology. No previous study has systematically evaluated associations between TH variation, semen parameters and ultrasound characteristics of the male genital tract.. Cross-sectional analysis of a consecutive series of 172 subjects seeking medical care for couple infertility from September 2010 to November 2014.. Of the entire cohort, 163 men (age 38.9 ± 8.0 years) free of genetic abnormalities were studied. All subjects underwent a complete andrological and physical examination, biochemical and hormonal assessment, scrotal and transrectal colour-Doppler ultrasound (CDUS) and semen analysis (including seminal interleukin 8 levels, sIL-8) evaluation within the same day.. Among the patients studied, 145 (88.9%) showed euthyroidism, 6 (3.7%) subclinical hyper- and 12 (7.4%) subclinical hypo-thyroidism. No subjects showed overt hyper- or hypo-thyroidism. At univariate analysis, no associations among thyroid-stimulating hormone (TSH) or TH levels and sperm parameters were observed. Conversely, we observed positive associations among free triiodothyronine (fT3) and free thyroxine (fT4) levels, ejaculate volume and seminal fructose levels. In a multivariate model, after adjusting for confounders such as age, body mass index, smoking habit, sexual abstinence, calculated free testosterone, prolactin and sIL-8 levels, only the associations found for fT3 levels were confirmed. When CDUS features were investigated, using the same multivariate model, we found positive associations between fT3 levels and seminal vesicles (SV) volume, both before and after ejaculation (adj. r = 0.354 and adj. r = 0.318, both P < 0.0001), as well as with SV emptying (ΔSV volume; adj. r = 0.346, P < 0.0001) and echo-texture inhomogeneity. In addition, after adjusting for confounders, negative associations between fT4 levels and epididymal body and tail diameters were found. No significant associations between TSH or TH levels and CDUS features of other organs of the male genital tract, including testis and prostate, were found. Finally, when the features of subjects with euthyroidism, subclinical hypo- and hyper-thyroidism were compared, no significant differences in seminal or hormonal parameters were found. Conversely, evaluating CDUS parameters, subjects with subclinical hyperthyroidism showed a higher difference between the SV longitudinal diameters measured before and after ejaculation when compared with that of subclinical hypothyroid men, even after adjusting for confounders (P < 0.007). All the other male genital tract CDUS characteristics did not differ among groups.. First, the number of patients investigated is relatively small and those with (subclinical) thyroid dysfunctions are an even smaller number; hence, it is therefore difficult to draw firm conclusions. Moreover, the present results are derived from patients consulting an Italian Andrology Clinic for couple infertility, and could have different characteristics from the male general population or from those males consulting general practitioners for reasons other than couple infertility. Finally, due to the cross-sectional nature of the study, neither a causality hypothesis nor mechanistic models can be inferred.. Although no associations between TH and sperm parameters were observed, present data support a positive effect of TH on SV size and a permissive role on the ejaculatory machinery, likely through an action on SV and epididymal contractility. This is the first study reporting such evidence. However, in contrast with the view that TH assessment is important for female fertility, our results do not support a systematic evaluation of thyroid function in males of infertile couples. How TH abnormalities impact male fertility needs to be addressed by further studies.. No funding was received for the study. None of the authors have any conflict of interest to declare.

Topics: Adult; Analysis of Variance; Cohort Studies; Cross-Sectional Studies; Fructose; Genitalia, Male; Humans; Infertility, Male; Interleukin-8; Male; Middle Aged; Multivariate Analysis; Semen; Semen Analysis; Testosterone; Thyroid Diseases; Thyroid Hormones

To evaluate leukocyte threshold values in semen to detect inflammation involving seminal interleukin (IL)-6 and IL-8.. The levels of leukocytes, IL-6, and IL-8 in semen were determined. The 75th and 90th percentiles of seminal IL-6 and IL-8 were considered as "high" and "very high" concentrations, respectively. Inflammatory semen was defined based on high levels of IL-6 (≥86.75 pg/mL) or IL-8 (≥4460 pg/mL). Very high levels of IL-6 (≥228 pg/mL) or IL-8 (≥12,480 pg/mL) were used to define acute seminal inflammation. On the basis of high and very high levels of IL-6 or IL-8, receiver operating characteristic curves were generated to evaluate leukocyte threshold values.. Leukocytes at a cutoff level of 1 × 10(6)/mL had 51% sensitivity and 95% specificity to detect high levels of IL-6, whereas on the basis of very high levels of IL-6, the same cutoff level revealed 82% sensitivity and 90% specificity. Similarly, leukocytospermia demonstrated low sensitivity (56%) to detect high levels of IL-8 but acceptable sensitivity (94%) and specificity (92%) to predict very high levels of IL-8. The cutoff level of 0.315 × 10(6) leukocytes/mL had optimal sensitivity and specificity for predicting high levels of inflammatory cytokines.. Leukocytospermia demonstrated poor sensitivity to detect seminal inflammation, as defined by high levels of inflammatory cytokines. The optimal threshold value to detect inflammation was found to be 0.315 × 10(6) leukocytes/mL. On the basis of very high levels of IL-6 or IL-8, leukocytospermia is a sensitive and specific marker to predict acute seminal inflammation.

Topics: Adult; Biomarkers; Follow-Up Studies; Humans; Infertility, Male; Inflammation; Interleukin-1; Interleukin-8; Leukocytes; Male; Retrospective Studies; ROC Curve; Semen

'Prostatitis-like symptoms' (PLS) are a cluster of bothersome conditions defined as 'perineal and/or ejaculatory pain or discomfort and National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) pain subdomain score ≥4' (Nickel's criteria). PLS may originate from the prostate or from other portions of the male genital tract. Although PLS could be associated with 'prostatitis', they should not be confused. The NIH-CPSI is considered the gold-standard for assessing PLS severity. Although previous studies investigated the impact of prostatitis, vesiculitis or epididymitis on semen parameters, correlations between their related symptoms and seminal or scrotal/transrectal colour-Doppler ultrasound (CDU) characteristics have not been carefully determined. And no previous study evaluated the CDU features of PLS in infertile men. This study was aimed at investigating possible associations among NIH-CPSI (total and subdomain) scores and PLS, with seminal, clinical and scrotal/transrectal CDU parameters in a cohort of males of infertile couples. PLS of 400 men (35.8 ± 7.2 years) with a suspected male factor were assessed by the NIH-CPSI. All patients underwent, during the same day, semen analysis, seminal plasma interleukin 8 (sIL-8, a marker of male genital tract inflammation), biochemical evaluation, urine/seminal cultures, scrotal/transrectal CDU. PLS was detected in 39 (9.8%) subjects. After adjusting for age, waist and total testosterone (TT), no association among NIH-CPSI (total or subdomain) scores or PLS and sperm parameters was observed. However, we found a positive association with current positive urine and/or seminal cultures, sIL-8 levels and CDU features suggestive of inflammation of the epididymis, seminal vesicles, prostate, but not of the testis. The aforementioned significant associations of PLS were further confirmed by comparing PLS patients with age-, waist- and TT-matched PLS-free patients (1 : 3 ratio). In conclusion, NIH-CPSI scores and PLS evaluated in males of infertile couples, are not related to sperm parameters, but mainly to clinical and CDU signs of infection/inflammation.

Topics: Adolescent; Adult; Epididymis; Epididymitis; Humans; Infertility, Male; Inflammation; Interleukin-8; Male; Middle Aged; Pelvic Pain; Prostate; Prostatitis; Retrospective Studies; Semen; Semen Analysis; Seminal Vesicles; Surveys and Questionnaires; Testis; Testosterone; Ultrasonography; Young Adult

To evaluate the role of pathogens and moderate leukocytes on seminal interleukin (IL)-6, IL-8, and sperm parameters in men undergoing infertility investigation.. Semen samples from men (n = 171) were divided into three groups on the basis of leukocyte count: no leukocytes (L-; ≤ 0.1 × 10(6)/ml Mio/ml), moderate leukocytes (L ±; >0.1 × 10(6)/ml and <1 × 10(6)/ml), and high leukocytes (=leukocytospermia) (L+; ≥ 1 × 10(6)/ml). Each group was further classified into two subgroups, according to the presence (B+) or absence (B-) of pathogens. IL-6, IL-8, and sperm characteristics were analyzed in each subgroup. A correlation test was performed to show the association between inflammatory parameters and sperm characteristics.. No significant differences in leukocyte count, cytokine levels, and sperm characteristics were apparent in subgroups with and without pathogens. Grade b motility was significantly lower in subgroup IIa (L ±,B-) than in subgroup Ia (L-,B-)(p < 0.05). More significant limitations in sperm motility (lower rapid progressive motility and increased percentage of immotile sperm) were observed in subgroup IIIa (L+,B-) compared with subgroup Ia (p < 0.05). Moderate and high leukocytes increased significantly cytokine levels (p < 0.001).. Moderate leukocyte counts could be an indicator of male genital tract inflammation. Seminal pathogens have no influence on cytokine levels and sperm parameters.

Topics: Adult; Bacteria; Humans; Infertility, Male; Interleukin-6; Interleukin-8; Leukocyte Count; Male; Semen; Semen Analysis

What are the associations between semen apoptotic M540 bodies and other parameters of semen quality and sonographic alterations of the male genital tract in a cohort of infertile subjects?. In infertile subjects, semen M450 bodies are highly correlated with ultrasound and clinical signs of testis abnormalities but not with alterations of other parts of the male genital tract, suggesting a testicular origin of M540 bodies.. We have reported the presence in semen of round anucleate elements, named 'M540 bodies', resembling apoptotic bodies as they contain several apoptotic markers.. A consecutive series of 130 males with couple infertility were evaluated, during the same day session, for clinical, scrotal and transrectal color-Doppler ultrasound characteristics, and hormonal and semen parameters, including interleukin 8 (sIL-8) and M540 body levels.. Semen parameters were analyzed by WHO recommended procedures. CDU was performed using the ultrasonographic console Hitachi H21. sIL-8 and serum hormones were evaluated by ELISA methods.. The average percentage value of M540 bodies was 24.6 ± 18.3. After adjusting for possible confounders (age, waist, calculated free testosterone and smoking habit), M450 body levels negatively correlated with sperm number/ejaculate, progressive motility, normal morphology and sIL-8 levels (adj.r = -0.455, P < 0.0001; adj.r = -0.464, P < 0.0001; adj.r = -0.430, P < 0.001; adj.r = -0.236, P < 0.05, respectively). In a subset of patients with a history of cryptorchidism (n = 8), M540 bodies were higher than in non-cryptorchid men (40.5 ± 14.8 versus 23.6 ± 18.2%; P < 0.02). A negative correlation was found between M540 and ultrasound testis volume (adj.r = -0.241, P < 0.05), whereas a positive association was found with testis inhomogeneity [HR = 1.06 (1.02-1.09); P = 0.002], hypoechogenicity [HR = 1.05 (1.01-1.08); P < 0.02] and FSH levels (adj.r = 0.309, P < 0.01). No relationships were found with CDU characteristic of the prostate, seminal vesicles, epididymis and vas deferens. In a multivariate model, testis inhomogeneity and history of cryptorchidism were independently associated with M540 body levels (adj.r = 0.355, P < 0.01 and adj.r = 0.223, P < 0.05, respectively). Receiver operating characteristic analysis demonstrated that at the threshold of 27%, M540 bodies discriminate subjects with testis inhomogeneity with a sensitivity of 72% and specificity of 73%.. The increased M540 body semen levels in men with a history of cryptorchidism should be confirmed in a larger number of patients.. M540 bodies may be considered a semen marker of altered testis function and thus their evaluation may be helpful in the diagnosis of male infertility.. This work was supported by grants from Ministry of University and Scientific Research (Prin project to E.B. and FIRB project to S.M.) and Regione Toscana (to G.F.).

Topics: Adult; Apoptosis; Cryptorchidism; Genitalia, Male; Humans; Infertility, Male; Interleukin-8; Male; Semen; Testis; Testosterone; Ultrasonography

This study was aimed at evaluating the association between seminal plasma interleukin-8 (sIL-8) and colour-Doppler ultrasound (CDU) characteristics of the male genital tract in a series of patients fulfilling the criteria of male accessory gland infections (MAGI). Of 250 subjects seeking medical care for couple infertility, 79 (mean age: 36.4 ± 7.5 years) met the criteria of MAGI and scored higher than the rest of the sample on the National Institutes of Health-Chronic Prostatitis Symptom Index score. All patients underwent simultaneous hormone evaluation and seminal analysis (including sIL-8), along with scrotal and transrectal CDU before and after ejaculation. After adjusting for age, sIL-8 in patients with MAGI was significantly related to several abnormal semen and CDU parameters. In particular, leucocytospermia was closely associated with sIL-8. Ejaculate volume, unlike other semen or hormonal parameters, was negatively associated with sIL-8. When scrotal CDU was performed, sIL-8 was positively related to CDU inhomogeneous, hypo-echoic, hyper-echoic epididymis and to epididymal calcifications. In addition, a positive correlation among sIL-8, hyperaemic epididymis and an increased size of epididymal tail was found. When transrectal CDU was performed, an association among sIL-8 and hyper-echoic seminal vesicles, dilated ejaculatory ducts and duct calcifications was also observed. Finally, sIL-8 was positively related to prostate CDU abnormalities such as calcifications, inhomogeneous/hypo-echoic texture, hyperaemia and high arterial blood flow. No association was found with testis parameters. In conclusion, sIL-8 levels in patients with MAGI are associated with several parameters and CDU abnormalities of epididymis, seminal vesicles, ejaculatory ducts and prostate, but not of the testis. Furthermore, sIL-8 positively correlates with CDU signs of ejaculatory duct inflammatory subobstruction.

Topics: Adult; Enzyme-Linked Immunosorbent Assay; Humans; Infertility, Male; Interleukin-8; Male; Semen; Ultrasonography, Doppler

Different cellular and biochemical markers have been proposed as indicators of infection-inflammation of male genital tract.. Semen samples from 80 men attending an andrologic clinic were evaluated to determine the presence of leukocyte, bacteria, antibodies against Chlamydia trachomatis, levels of IL-6, IL-8, IL-10, and TNF-alpha, HSP-60, anti-HSP-60 antibodies, and anti-sperm antibodies.. Leukocytes in semen significantly correlated with an increase in IL-6, IL-8, and TNF-alpha. The simultaneous presence of pathogens and leukocytes was associated with high levels of IL-8 and TNF-alpha, whereas IL-6 was more associated with the presence of leukocytes. Anti-HSP-60 antibodies positively correlated with IL-6 and IL-8. The presence of anti-sperm antibodies highly associated with an increase in anti-HSP-60 antibodies.. The type of cytokines present in the semen will depend on the single or simultaneous presence of leukocytes and/or pathogens. Chronic male genital tract infections could be associated with the development of anti-HSP-60 antibodies and anti-sperm antibodies.

Topics: Adult; Antibodies; Chaperonin 60; Chlamydia Infections; Chlamydia trachomatis; Cytokines; Humans; Infertility, Male; Interleukin-10; Interleukin-6; Interleukin-8; Leukocytes; Male; Middle Aged; Spermatozoa; Tumor Necrosis Factor-alpha; Venezuela

We directly injected DNA into mouse testes in vivo using an adenovirus vector to transfect testicular cells. We then analyzed the transfection efficiency, immunological problems and effects of gene transfer on spermatogenesis and the next generation. In this study we discuss the potential of gene therapy for male infertility.. A replication incompetent human adenovirus serotype 5 contained 2 deletions (E1 and E3 deletions) and was constructed such that the transgene was driven by the chicken beta-actin promoter to promote over expression of the downstream target gene (Lac Z). This adenovirus vector or control solution was injected into the interstitial space (intratesticular injection) or seminiferous tubules (intratubular injection) of the mouse testis. We investigated beta-galactosidase gene expression by X-gal (5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside) staining, the effects of gene transfer on spermatogenesis by evaluating the frequency of apoptotic cells by the TUNEL method, the inflammatory response on testes by detecting CD4 and CD8 positive cells immunohistochemically, and interleukin (IL)-6 and IL-8 by immunoblot analysis, epididymides sperm motility and the reproductive response of each mouse 3, 7, 14 and 28 days after injection.. Intratesticular injection of adenovirus vector resulted in strong transgene expression in Leydig cells. In contrast, intratubular injection resulted in strong expression in Sertoli cells. Transgene expression was not detected in germ cells by either method. The peak of beta-galactosidase activity was on day 7, ie 0.674 +/- 0.20 (intratesticular) and 0.534 +/- 0.22 U (intratubular), and it decreased with time thereafter. The apoptosis index on day 7 was significantly higher in adenovirus injected groups than in noninjected groups, ie 0.46 +/- 0.20 vs 0.10 +/- 0.11 (intratesticular) and 0.78 +/- 0.31 vs 0.24 +/- 0.10 (intratubular). Transfected animals showed a slight mononuclear inflammatory response in the testes composed of CD4 and CD8 positive cells. Adenovirus vector stimulation resulted in the induction of IL-6 and IL-8 secretion in the testis. These immune responses subsided after day 7. There were no significant differences in the percent of motile sperm or the rate of abnormal sperm between the groups on any day after injection. Reproductive ability remained almost normal even after adenovirus mediated gene transfer with no effect observed in offspring.. Our results suggest that although slight spermatogenic damage and inflammatory response caused by these methods may present problems, adenovirus mediated gene transfer may be effective for transfecting testicular somatic cells and applicable for in vivo gene therapy for male infertility in the future.

Topics: Adenoviruses, Human; Animals; Animals, Newborn; Apoptosis; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Female; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Humans; Infertility, Male; Injections; Interleukin-6; Interleukin-8; Leydig Cells; Male; Mice; Mice, Inbred ICR; Pregnancy; Sertoli Cells; Sperm Motility; Spermatogenesis; Testis

To evaluate the effect of nitric oxide (NO), TNF alpha, IL-6, IL-8 on the pathogenesis of infertile men.. NO, TNF alpha, IL-6 and IL-8 levels were assayed in 80 infertile men and 26 normal men.. The levels of NO, TNF alpha, IL-6 and IL-8 in infertile men were all significantly higher than those in controls (P < 0.01 or P < 0.05). NO was positively correlated with TNF alpha, IL-6 and IL-8 (P < 0.01).. NO, TNF alpha, IL-6 and IL-8 might play an important role in the pathogenic process of infertile.

Topics: Adult; Cytokines; Humans; Infertility, Male; Interleukin-6; Interleukin-8; Male; Middle Aged; Nitric Oxide; Semen; Tumor Necrosis Factor-alpha

Fractalkine is a relatively newly discovered CX(3)C chemokine, which is a chemoattractant for T cells, monocytes and natural killer cells. Several reports have demonstrated the association between chemokine levels in seminal plasma and semen quality. The fractalkine levels in ejaculates from normal donors and infertile male patients with or without asthenozoospermia, were examined and correlated with sperm motility and morphology.. Western blot analysis showed fractalkine protein to be present in the seminal plasma. Fractalkine titres in the seminal plasma of infertile men with asthenozoospermia (0.64 +/- 0.04 microg/ml; n = 58) were lower than those in patients without asthenozoospermia (0.94 +/- 0.10 microg/ml; n = 22, P < 0.01) and fertile donors (1.04 +/- 0.07 microg/ml; n = 10, P < 0.001). There was no significant difference between fractalkine levels in patients with and without leukospermia. No significant correlation was found between fractalkine and interleukin-8 levels in seminal plasma. Sperm motility was positively correlated (R(2) = 0.14, P < 0.001) with fractalkine concentration. The existence of CX(3)CR-positive leukocytes in semen was confirmed using specific primers for CX(3)CR.. These results suggest that fractalkine is a chemokine associated with sperm motility and the migration of CX(3)CR-positive leukocytes into semen.

Topics: Base Sequence; Case-Control Studies; Chemokine CX3CL1; Chemokines, CX3C; Gene Expression; Humans; Infertility, Male; Interleukin-8; Leukocytes; Male; Membrane Proteins; RNA, Messenger; Semen; Sperm Motility

The aim of this study was to determine the presence and concentration of interleukin IL-6, IL-8, and granulocyte-macrophage-colony-stimulating factor (GM-CSF) in pre-ovulatory ovarian follicular fluid (FF) of patients undergoing controlled ovarian hyperstimulation for intracytoplasmic sperm injection (ICSI) therapy on one hand, and to find out whether these cytotokine concentrations could be used as a predictive parameter for ICSI outcome.. The levels of IL-6, IL-8, and GM-CSF were measured from women that underwent ICSI therapy and the results were compared between the patients who became pregnant after IC

Topics: Adult; Female; Follicular Fluid; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Infertility, Male; Interleukin-6; Interleukin-8; Interleukins; Male; Pregnancy; Prognosis; Sperm Injections, Intracytoplasmic

Fertilization and oocyte cleavage rates have previously been demonstrated to be lower for women with endometriosis undergoing IVF compared with controls. This might be related to impaired oocyte function, possibly due to an inflammatory milieu in the pelvis of these women, where an elevated concentration of many cytokines is documented. The aim of this study was to examine whether granulosa cells from women with endometriosis deviated with respect to production of the inflammatory cytokines interleukin-1beta, interleukin-6, interleukin-8 and tumour necrosis factor alpha (TNFalpha) compared with granulosa cells from healthy women, undergoing IVF for male infertility. The effect of human chorionic gonadotrophin on cytokine production was also investigated. Granulosa cells in follicular fluid were obtained at oocyte retrieval for IVF. Incubated cell culture media were analysed by enzyme-linked immunosorbent assay. The basal production of all four cytokines was higher in cells from women with endometriosis when compared to controls, although the increase was only significant for TNFalpha. Chorionic gonadotrophin had no significant effect, although it had a tendency to suppress cytokine release in both patient categories. Whether aberrant cytokine production in granulosa cells from women with endometriosis may disturb fertilizing capacity of oocytes requires study.

Topics: Adult; Cells, Cultured; Chorionic Gonadotropin; Cytokines; Endometriosis; Female; Fertilization in Vitro; Granulosa Cells; Humans; Infertility, Female; Infertility, Male; Interleukin-1; Interleukin-6; Interleukin-8; Male; Pregnancy; Pregnancy Rate; Reference Values; Tumor Necrosis Factor-alpha

To investigate the effect of antibiotic therapy on seminal infection.. The seminal plasma of 50 men was evaluated in three groups: (1) men with seminal infection (20), (2) men with leukocytospermia only (18), and (3) men of proven fertility (12). The evaluation protocol included semen analysis, culture and antibiotic sensitivity test, total antioxidant activity, alpha-tocopherol and retinol, T-helper cytokines, IL-2, IL-8, IL-4 and antisperm antibodies.. Sperm parameters were worse with seminal infection: 25 versus 84 million per milliliter for fertile men. Antioxidant activity, total alpha-tocopherol and retinol were reduced in leukocytospermia (P < .02, .01) and seminal infection (P < .01, .05) as compared to controls. Antisperm antibodies IL-2 and IL-8 were highly expressed, while IL-4 was low in men with leukocytospermia and bacteriospermia. Gram-negative organisms were more associated with expression of T-helper 1 cytokines than T-helper 2 cytokines. Antibiotic therapy significantly improved the sperm parameters, antioxidant activity and IL-4 but reduced IL-2 and IL-8 and had no effect on antisperm antibody titer.. Antibiotic therapy improves sperm parameters by increasing antioxidant activity and IL-4 and by reducing IL-2 and IL-8.

Topics: Adult; Anti-Bacterial Agents; Antioxidants; Bacterial Infections; Humans; Infertility, Male; Interleukin-2; Interleukin-4; Interleukin-8; Male; Semen; Spermatozoa; Vitamin A; Vitamin E

The role of cell-mediated immunity in the aetiopathogenesis of male infertility is far from being defined. The cytochemokine interleukin-8 (IL-8) has a key role in T-cell mediated immune responses. The aim of this study was to confirm the presence of IL-8 in human seminal plasma, to show differences between IL-8 concentrations in fertile and infertile subjects, and to show the potential relationship between IL-8 amounts in semen and spermiogram parameters. IL-8 levels were determined in the seminal plasma of 77 men divided as follows: (a) into seven groups according to the aetiological diagnosis of fertility and (b) into two groups on the basis of a normal or abnormal spermiogram. The mean value of IL-8 in the seminal plasma was 31.5 times higher than the upper limit in normal serum. There is a borderline statistical significant difference among the means of the various groups (P < 0.051). The Tukey's HSD test for multiple comparisons indicated no two groups as being significantly different, whereas the less conservative test LSD showed significant differences between the group with infection and groups with normal controls, Klinefelter's syndrome, mumps orchitis, cryptorchidism, or varicocele. There was no significant difference in IL-8 levels between men with normal and those with abnormal spermiograms. Furthermore, there was no correlation between IL-8 levels and the variables of the spermiogram. Even though the conclusions of this study have to be tempered by the sample size, IL-8 concentration in seminal plasma may be considered as a potential marker for the diagnosis of male accessory gland infection.

Topics: Adolescent; Adult; Cryptorchidism; Humans; Immunity, Cellular; Infertility, Male; Interleukin-8; Klinefelter Syndrome; Male; Middle Aged; Mumps; Reference Values; Semen; Varicocele

To quantify the levels of reactive oxygen species, superoxide dismutase (SOD), and interleukins (IL) 2 and 8 in seminal plasma of infertile patients as well as to examine the possible relationship between oxidative stress and proinflammatory cytokines.. Semen collected from normal fertile donors, infertile men without symptoms of genitourinary (GU) inflammation, and infertile men with symptoms of infection-inflammation of the GU tract was evaluated for the levels of granulocyte elastase, reactive oxygen species, SOD, IL-2, and IL-8. Any correlation between the levels of reactive oxygen species and other parameters in these population was analyzed statistically.. Significantly high levels of granulocyte elastase (18.32 +/- 1.52 U/L), reactive oxygen species (6 x 10(5) cpm), IL-8 (3.7 +/- 0.10 microgram/L), and IL-2 (18.32 +/- 1.47 ng/L) were observed in semen of infertile patients with leukocytospermia compared with the other two groups. In leukocytospermic samples, the activity of SOD was significantly lower (624.89 +/- 41.16 NU/mL) compared with nonleukocytospermic samples (787.85 +/- 24.26 NU/mL) or fertile donors (816.29 +/- 50.16 NU/mL). A significant positive correlation was observed between the levels of reactive oxygen species and IL-8.. These findings suggest that increased oxidative stress observed during leukocytospermia may modulate the level of proinflammatory cytokines. The increased oxidative stress may be due to a defect in the reactive oxygen species scavenging system.

Topics: Humans; Infertility, Male; Interleukin-2; Interleukin-8; Interleukins; Leukocyte Elastase; Leukocytes; Male; Male Urogenital Diseases; Neutrophils; Oxidative Stress; Pancreatic Elastase; Reactive Oxygen Species; Semen; Superoxide Dismutase

To demonstrate whether monocyte chemotactic and activating factor (MCAF) and interleukin-6 (IL-6) are present in the seminal plasma, and whether these presence is modulated by leukospermia.. Semen samples from 53 men were obtained by masturbation and examined for the presence of MCAF and IL-6 by enzyme immunoassay (EIA). Semen samples were obtained from 28 infertile men without leukospermia, 16 infertile men with leukospermia, and nine proven-fertile men. The correlation between the amount of MCAF in the seminal plasma with some spermiogram parameters and other cytokines such as IL-6 and IL-8 was statistically evaluated.. Immunoreactive MCAF was detected in the seminal plasmas of all 53 subjects. The MCAF titer in the seminal plasma of patients with leukospermia (11.19 +/- 2.75 micrograms/l) was significantly higher than that in the seminal plasma of the patients without leukospermia (3.24 +/- 0.53 micrograms/l) and the fertile men (2.78 +/- 0.35 micrograms/l) (P < 0.001). The IL-6 titer in the seminal plasma of the patients with leukospermia (21.05 +/- 4.49 ng/l) was also significantly higher than that in the seminal plasma of the patients without leukospermia (8.77 +/- 1.92 ng/l) and the fertile men (6.94 +/- 1.27 ng/l) (P < 0.01). There was a high degree of correlation among the levels of MCAF, IL-6 and IL-8 in the seminal plasma.. These findings demonstrated the presence of MCAF and IL-6 in the seminal plasma, and that the levels of these cytokines were elevated in the seminal plasma of the infertile patients with leukospermia.

Topics: Chemokine CCL2; Humans; Infertility, Male; Interleukin-6; Interleukin-8; Leukocyte Count; Leukocytes; Male; Semen; Sperm Count; Sperm Motility

To determine if interleukin-8 (IL-8) is a normal constituent of seminal plasma and if leukospermia is a factor determining its elevation.. Seminal plasma from 58 men obtained by masturbation was examined for the presence of IL-8 using an IL-8 specific sandwich ELISA. Semen samples were obtained from 34 infertile men without leukospermia, 10 infertile men with leukospermia, and 14 proven fertile men. The correlation of amount of IL-8 in seminal plasma with some spermiogram parameters and the amount of polymorphonuclear (PMN) elastase was statistically evaluated.. Immunoreactive IL-8 was observed in the seminal plasma of all 58 subjects. The IL-8 titer in seminal plasma of patients with leukospermia (6.16 +/- 0.82 micrograms/L) was significantly higher than that in seminal plasma of patients without leukospermia (2.35 +/- 0.34 micrograms/L) and fertile men (1.64 +/- 0.29 micrograms/L). There was a high degree of correlation between PMN elastase and IL-8 levels in seminal plasma.. These findings demonstrate IL-8 to be in seminal plasma and elevated IL-8 levels in infertile patients with leukospermia.

Topics: Humans; Infertility, Male; Interleukin-8; Leukocyte Elastase; Leukocytes; Male; Pancreatic Elastase; Semen