Testicular immune cell populations and macrophage polarisation in adult male mice and the influence of altered activin A levels.

Detailed morphological characterization of testicular leukocytes in the adult CX3CR1 gfp/+ transgenic mouse identified two distinct CX3CR1 + mononuclear phagocyte (macrophage and dendritic cell) populations: stellate/dendriform cells opposed to the seminiferous tubules (peritubular), and polygonal cells associated with Leydig cells (interstitial). Using confocal microscopy combined with stereological enumeration of CX3CR1gfp/+ cells established that there were twice as many interstitial cells (68%) as peritubular cells (32%). Flow cytometric analyses of interstitial cells from mechanically-dissociated testes identified multiple mononuclear phagocyte subsets based on surface marker expression (CX3CR1, F4/80, CD11c). These cells comprised 80% of total intratesticular leukocytes, as identified by CD45 expression. The remaining leukocytes were CD3+ (T lymphocytes) and NK1.1+ (natural killer cells). Functional phenotype assessment using CD206 (an anti-inflammatory/M2 marker) and MHC class II (an activation marker) identified a potentially tolerogenic CD206+MHCII+ sub-population (12% of total CD45+ cells). Rare testicular subsets of CX3CR1 +CD11c+F4/80+ (4.3%) mononuclear phagocytes and CD3+NK1.1+ (3.1%) lymphocytes were also identified for the first time. In order to examine the potential for the immunoregulatory cytokine, activin A to modulate testicular immune cell populations, testes from adult mice with reduced activin A (Inhba+/-) or elevated activin A (Inha+/-) were assessed using flow cytometry. Although the proportion of F4/80+CD11b+ leukocytes (macrophages) was not affected, the frequency of CD206+MHCII+cells was significantly lower and CD206+MHCII- correspondingly higher in Inha+/- testes. This shift in expression of MHCII in CD206+ macrophages indicates that changes in circulating and/or local activin A influence resident macrophage activation and phenotype and, therefore, the immunological environment of the testis.

[Andrological diagnostics prior to treatment by assisted reproduction]. / Andrologische Diagnostik vor einer reproduktionsmedizinischen Behandlung.

Infertility is defined as the inability of a couple to succeed in achieving a spontaneous pregnancy after 1 year. Male and female factors contribute to infertility with approximately 40% each. In the remaining cases factors that affect fertility can be found in both partners. The andrological work-up should be started simultaneously with the gynecological diagnostic procedure in order to identify and treat andrological factors related to infertility. Since the majority of intracytoplasmic sperm injection procedures are performed due to andrological infertility, andrological diagnostics can prevent a delay in assisted reproductive technology. The andrological work-up can be necessary before 12 months of unsuccessful conception if the female partner is older than 35 years or andrological factors are present that could impair male fertility.

CCL20-CCR6 axis directs sperm-oocyte interaction and its dysregulation correlates/associates with male infertility‡.

The interaction of sperm with the oocyte is pivotal during the process of mammalian fertilization. The limited numbers of sperm that reach the fallopian tube as well as anatomic restrictions indicate that human sperm-oocyte encounter is not a matter of chance but a directed process. Chemotaxis is the proposed mechanism for re-orientating sperm toward the source of a chemoattractant and hence to the oocyte. Chemokines represent a superfamily of small (8-11 kDa), cytokine-like proteins that have been shown to mediate chemotaxis and tissue-specific homing of leukocytes through binding to specific chemokine receptors such as CCRs. Here we show that CCR6 is abundantly expressed on human sperms and in human testes. Furthermore, radioligand-binding experiments showed that CCL20 bound human sperm in a specific manner. Conversely, granulosa cells of the oocyte-surrounding cumulus complex as well as human oocytes represent an abundant source of the CCR6-specific ligand CCL20. In human ovaries, CCL20 shows a cycle-dependent expression pattern with peak expression in the preovulatory phase and CCL20 protein induces chemotactic responses of human sperm. Neutralization of CCL20 in ovarian follicular fluid significantly impairs sperm migratory responses. Conversely, analyses in infertile men with inflammatory conditions of the reproductive organs demonstrate a significant increase of CCL20/CCR6 expression in testis and ejaculate. Taken together, findings of the present study suggest that CCR6-CCL20 interaction may represent an important factor in directing sperm-oocyte interaction.

[Orchitis]. / Hodenentzündung.

Orchitis can be acutely symptomatic or chronically asymptomatic. Among the acute forms is the rarer isolated orchitis, which is of viral origin in most cases as well as the more frequent secondary orchitis, which is usually the result of an ascending bacterial epididymitis. In addition, sterile forms of orchitis are also seen in patients with systemic autoimmune comorbidities. Chronic asymptomatic orchitis is the term used to describe cellular immune infiltrates in the testes, which are observed in approximately 25% of cases of azoospermia during testicular biopsy. The etiopathogenesis of these infiltrates is largely unknown with postinfection and primary pathogen-independent autoimmune reactions being discussed. Animal experimental models of orchitis may be helpful to investigate the immunological mechanisms involved as well as the therapeutic possibilities.

Activin A target genes are differentially expressed between normal and neoplastic adult human testes: clues to gonocyte fate choice.

BACKGROUND: Human testicular germ cell tumours (TGCT) arise from germ cell neoplasia in situ (GCNIS) cells that originate from foetal germ cell precursors. Activin A is central to normal foetal testis development, and its dysregulation may contribute to TGCT aetiology. OBJECTIVE: (i) To test whether the expression profiles of activin A targets in normal and neoplastic human testes indicates functional links with TGCT progression. (ii) To investigate whether activin A levels influence MMP activity in a neoplastic germ cell line. MATERIALS AND METHODS: (1) Bouin's fixed, paraffin-embedded human testes were utilized for PCR-based transcript analysis and immunohistochemistry. Samples (n = 5 per group) contained the following: (i) normal spermatogenesis, (ii) GCNIS or (iii) seminoma. CXCL12, CCL17, MMP2 and MMP9 were investigated. (2) The human seminoma-derived TCam-2 cell line was exposed to activin A (24 h), and target transcripts were measured by qRT-PCR (n = 4). ELISA (n = 4) and gelatin zymography (n = 3) showed changes in protein level and enzyme activity, respectively. RESULTS: (i) Cytoplasmic CXCL12 was detected in Sertoli and other somatic cells, including those surrounding seminoma cells. Anti-CCL17 labelled only the cytoplasm of Sertoli cells surrounding GCNIS, while anti-MMP2 and anti-MMP9 labelled germline and epithelial-like cells in normal and neoplastic testes. (ii) Exposing TCam-2 cells to activin A (50 ng/mL) elevated MMP2 and MMP9 transcripts (fourfold and 30-fold), while only MMP2 protein levels were significantly higher after activin A (5 ng/mL and 50 ng/mL) exposure. Importantly, gelatin zymography revealed activin A increased production of activated MMP2. DISCUSSION: Detection of CCL17 only in GCNIS tumours may reflect a change in Sertoli cell phenotype to a less mature state. Stimulation of MMP2 activity by activin A in TCam-2 cells suggests activin influences TGCT by modulating the tumour niche. CONCLUSION: This knowledge provides a basis for understanding how physiological changes that influence activin/TGF-ß superfamily signalling may alter germ cell fate.

[Impact of lifestyle and environmental factors on male reproductive health]. / Einfluss von Lebensstil und Umweltfaktoren auf die reproduktive Gesundheit des Mannes.

The identification of potential environmental hazards may be clinically relevant in the diagnosis of male infertility. Knowledge about these factors will improve prevention of fertility disorders. Apart from drugs or factors related to lifestyle such as alcohol and tobacco smoke, various environmental and occupational agents, both chemical and physical, may impair male reproductive function. Reproductive toxicity may evolve at the hypothalamic-pituitary, testicular, or post-testicular level; endpoints comprise deterioration of spermatogenesis and sperm function as well as endocrine disorders and sexual dysfunction. With regard to the complex regulation of the male reproductive system, the available information concerning single exogenous factors and their mechanisms of action in humans is limited. This is also due to the fact that extrapolation of results obtained from experimental animal or in vitro studies remains difficult. Nevertheless, the assessment of relevant exposure to reproductive toxicants should be carefully evaluated during diagnostic procedures of andrological patients.

An in vitro model demonstrates the potential of neoplastic human germ cells to influence the tumour microenvironment.

Testicular germ cell tumours (TGCT) typically contain high numbers of infiltrating immune cells, yet the functional nature and consequences of interactions between GCNIS (germ cell neoplasia in situ) or seminoma cells and immune cells remain unknown. A co-culture model using the seminoma-derived TCam-2 cell line and peripheral blood mononuclear cells (PBMC, n = 7 healthy donors) was established to investigate how tumour and immune cells each contribute to the cytokine microenvironment associated with TGCT. Three different co-culture approaches were employed: direct contact during culture to simulate in situ cellular interactions occurring within seminomas (n = 9); indirect contact using well inserts to mimic GCNIS, in which a basement membrane separates the neoplastic germ cells and immune cells (n = 3); and PBMC stimulation prior to direct contact during culture to overcome the potential lack of immune cell activation (n = 3). Transcript levels for key cytokines in PBMC and TCam-2 cell fractions were determined using RT-qPCR. TCam-2 cell fractions showed an immediate increase (within 24 h) in several cytokine mRNAs after direct contact with PBMC, whereas immune cell fractions did not. The high levels of interleukin-6 (IL6) mRNA and protein associated with TCam-2 cells implicate this cytokine as important to seminoma physiology. Use of PBMCs from different donors revealed a robust, repeatable pattern of changes in TCam-2 and PBMC cytokine mRNAs, independent of potential inter-donor variation in immune cell responsiveness. This in vitro model recapitulated previous data from clinical TGCT biopsies, revealing similar cytokine expression profiles and indicating its suitability for exploring the in vivo circumstances of TGCT. Despite the limitations of using a cell line to mimic in vivo events, these results indicate how neoplastic germ cells can directly shape the surrounding tumour microenvironment, including by influencing local immune responses. IL6 production by seminoma cells may be a practical target for early diagnosis and/or treatment of TGCT.

Metabolic syndrome and the seminal cytokine network in morbidly obese males.

Given the increasing prevalence of metabolic syndrome (MetS) in males of reproductive age, the objective of this prospective case-controlled study was to investigate the impact of subacute systemic inflammation associated with MetS on seminal cytokines and standard sperm parameters in comparison with healthy men. Between 2011 and 2014, we recruited 27 patients with MetS out of 41 obese patients screened from an internal outpatient clinic. Twenty-seven age-matched healthy controls were enrolled from 54 men requesting vasectomy in a urological outpatient clinic. A multiplex analysis was performed to quantify simultaneously the level of 30 cytokines (Eotaxin, FGF, Fraktalkine, GCSF, GMCSF, Granzyme A, IFN-γ, IL-1α, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-17A, IL-21, IP-10, I-TAC, MCP-1, MIG, MIP-1α, MIP-1ß, RANTES, TNF-α, and VEGF) in each 50 µL of blood and seminal plasma during the andrological work-up. Semen analysis was performed according to the WHO (Global status report on noncommunicable diseases, 2010) recommendations, including standard sperm parameters as well as peroxidase-positive leukocytes and polymorphonuclear elastase. Blood levels of C-reactive protein, interleukins 6 and 10 were elevated in MetS (p > 0.001). Two-way hierarchical cluster analysis showed characteristic cytokine networks in semen greatly differing from those in blood, but not between MetS and controls. No deterioration of semen analysis was evident in men diagnosed with MetS. Our results suggest that there is no transmission of the systemic inflammation associated with MetS into semen based on cytokine profiles and that MetS does not impair standard semen parameters to a clinically significant extent.

[Environmental factors and male fertility]. / Umweltfaktoren und männliche Fertilität.

BACKGROUND: The identification of potential environmental hazards may have clinical relevance for diagnosis of male infertility. Knowledge about these factors will improve prevention of fertility disorders. RESULTS: Apart from drugs or factors related to lifestyle such as alcohol and tobacco smoke, various environmental and occupational agents, both chemical and physical, may impair male reproductive functions. With regard to the complex regulation of the male reproductive system, the available information concerning single exogenous factors and their mechanisms of action in humans is limited. This is also due to the fact that extrapolation of results obtained from experimental animal studies remains difficult. CONCLUSION: Nevertheless, the assessment of relevant exposures to reproductive toxicants should be carefully evaluated during diagnostic procedures of andrological patients.

[Infection and infertility]. / Infektionen und Infertilität.

BACKGROUND: Infections in the urogenital tract are accepted causes of male infertility. Epidemiologic data indicate 6-10 % of all males undergoing andrological work-up for infertility having an infectious etiology. TOPICS: This review gives a comprehensive overview on the most important urogenital tract infections (prostatitis, epididymitis, orchitis, male accessory gland infection-MAGI) and the impact on fertility. In males suffering infertility, evidence is also presented regarding an infectious etiology.

The impact of sperm protamine deficiency and sperm DNA damage on human male fertility: a systematic review and meta-analysis.

Existing literature suggests evidence that protamine deficiency is related to DNA damage and male fertility. In this meta-analysis, we analyzed the relationship between the ratio of protamine-1 and protamine-2 with male fertility and the association of protamine deficiency with sperm DNA damage. Quality of available cohort studies was evaluated using the Newcastle-Ottawa Scale checklist. Summary effect estimates with 95% confidence intervals (CI) were derived using a random effects model. The effect of the protamine ratio on male fertility was analyzed in nine studies demonstrating a significantly higher value of the protamine ratio in subfertile men (n = 633) when compared with controls (n = 453, SMD = 0.46, 95% CI 0.25-0.66, Z = 4.42, p < 0.00001). Both protamine mRNA (SMD = 0.45, 95% CI 0.11-0.79, Z = 2.63, p = 0.009) and protein ratio (SMD = 0.46, 95% CI 0.25-0.68, Z = 4.22, p < 0.0001) showed significantly increased values in subfertile patients. The association between protamine deficiency and DNA damage was analyzed in 12 studies (n = 845) exhibiting a combined overall correlation coefficient (COR) of 0.53 (95% CI 0.28-0.71, Z = 3.87, p < 0.001). Protamine deficiency measured by CMA3 staining was significantly associated with sperm DNA damage (COR = 0.71, 95% CI 0.48-0.85, Z = 4.87, p < 0.001), whereas the P1/P2 ratio was not (COR = 0.17, 95% CI -0.16 to 0.46, Z = 0.99, p = 0.33). It is concluded that the protamine ratio represents a suitable biomarker for the assessment of sperm quality and protamine deficiency is closely related with sperm DNA damage.

[Current Aspects of Epididymo-Orchitis]. / Aktuelle Aspekte der Epididymo-Orchitis.

BACKGROUND: Acute epididymitis is an inflammation of the epididymis. It mostly occurs unilaterally and may spread to the testis ('epididymo-orchitis') if untreated. Increasing technological advances allow for an even more detailed examination of concurrent symptoms such as ejaculate changes and the whole spectrum of pathogenic agents, which ranges from sexually transmitted pathogens such as Chlamydia and gonococci to enterobacteria and, rarely, viruses. This review summarises major aspects of the disease including the latest scientific findings. METHODS: A selective literature search including the last 40 years was performed via Medline. RESULTS: With about 400 cases a year in 100 000 men, acute epididymitis is the most common urogenital infection in men. It occurs across all age groups including children. Despite the fact that bacterial ascension is aetiologically of utmost relevance, only one out of three men reports signs of dysuria or urethritis. In young, sexually active men, sexually transmitted pathogens are regularly found in addition to the characteristic enterobacteriae, even if these men have an unremarkable sexual history. 88% of epididymal abscess formations can be successfully treated without surgery. Patients with indwelling urethral catheters are at a high risk of multiple drug resistance and should be treated empirically with both a fluoroquinolone and a third-generation cephalosporin until antimicrobial susceptibility testing has been completed. About 40 out of 100 patients develop post-inflammatory sub-fertility. Here, virulence factors like haemolysin A produced by uropathogenic E. coli have a negative impact on semen parameters compared to those patients suffering from epididymitis induced by haemolysin A negative strains. With adequate antibiotic treatment there is no evidence for testicular atrophy. Only one out of 10 men relapses. These cases should be examined thoroughly for subvesical obstruction. Some of them may benefit from prophylactic vasectomy. CONCLUSIONS: This review presents key aspects of acute epididymitis, which are increasingly adopted in updated guidelines.

[Dermatological diseases and sexuality. How to proceed?]. / Dermatologische Erkrankungen und Sexualität. Wie geht man vor?

A variety of dermatological diseases is associated with male or female sexual dysfunction. Some sexual disorders are caused organically; erectile dysfunction in men with systemic sclerosis may be due to penile vascular alterations and corporal fibrosis. Other dermatoses such as psoriasis are associated with risk factors (metabolic syndrome) for sexual disorders and may therefore indirectly induce erectile dysfunction. However, the majority of sexual dysfunctions in dermatological patients is caused by reduced self confidence and sexual self esteem leading to affected partnership and sexuality. Dermatologists should be trained in basic sexual medicine and ask their patients for sexual problems. They may not treat sexual disorders, but they should be identified as sympathetic physicians for these problems and should be able to refer the patient to specialists in sexual medicine.

Experimental Escherichia coli epididymitis in rats: assessment of testicular involvement in a long-term follow-up.

The objective of this study was to investigate spermatogenesis and testicular inflammation in a rat model of unilateral Escherichia coli epididymitis in a long-term follow-up. Unilateral epididymitis was induced in 30 Sprague-Dawley rats by injecting E. coli into the right ductus deferens. Oral antimicrobial treatment with sparfloxacin (50 mg kg(-1) body weight/7 days) was administered in half of the animals 24 h after infection. Five treated and five untreated rats were killed at 2 weeks, 3 months and 6 months after infection. Spermatogenesis was investigated using a histological semi-quantitative score. The presence of inflammatory cells (B- and T lymphocytes, macrophages and granulocytes) in the testicular tissues was evaluated by immunohistochemistry. The testes were sterile at all times. Over the course of 6 months, spermatogenesis underwent significant incremental impairment on the inoculated side as compared to the contralateral side (P < 0.001). However, overall spermatogenesis scores were not significantly different between treated and untreated animals (P > 0.3 at each time point). Finally, loss of testicular architecture on the inoculated side was not associated with any cellular inflammatory response. Thus, adjuvant therapies need to be studied, and research is necessary on how to prevent deterioration of testicular function in bacterial epididymitis.

Validation of the German version of the 'Hypogonadism Related Symptom Scale' (HRS) in andrological patients with infertility, HIV infection and metabolic syndrome.

As commonly used self-reported screening instruments for male hypogonadism demonstrated lack of specificity, a Hypogonadism Related Symptom Scale (HRS) was developed in 2009 as a novel self-rating screening tool. As the questionnaire has not been validated, the purpose of our study was to perform a validation in patients presenting with different disorders (e.g. infertility, HIV infection or metabolic syndrome) and disease-related risk to develop hypogonadism. Two hundred and eighteen patients aged 19-71 years (40.1 ± 9.5) who completed the HRS and other common questionnaires [International Index Of Erectile Function (IIEF), National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), Hospital Anxiety and Depression Scale (HADS), short form (SF)-12] were included. In all patients, blood levels of total testosterone, luteinizing hormone, follicle-stimulating hormone, oestradiol and sex hormone-binding globulin were determined and free testosterone was calculated. Cronbach's α for the scale was 0.896, split-half 0.871 for the 1st half and 0.807 for the 2nd half. Spearman-Brown coefficient was 0.767, and Guttman split-half coefficient was 0.759. Consistent correlations were found between HRS and IIEF5 (ρ = 0.57, P < 0.001), and HADS (ρ = -0.6, P < 0.001). In addition, HRS was significantly correlated with total testosterone (ρ = 0.135, P < 0.05), free testosterone (ρ = 0.148, P < 0.05) and oestradiol (ρ = -0.134, P < 0.05). Our validation study confirms the data from the initial development of the HRS questionnaire. Clinicians might have an additional advantage from the HRS when investigating males with suspected hypogonadism.

Differential leucocyte detection by flow cytometry improves the diagnosis of genital tract inflammation and identifies macrophages as proinflammatory cytokine-producing cells in human semen.

Genital tract inflammation is considered as a major cause of male infertility with leucocytospermia as widely used diagnostic marker. However, threshold of 10(6) leucocytes ml(-1) recommended by the WHO is a matter of debate. Moreover, leucocyte subpopulations and their impact cannot be identified by the routine peroxidase method (POM). Ejaculates of subfertile men (n = 47) were analysed by flow cytometry (FACS) using a bead-based method. Leucocytes were identified by CD18 and further divided into macrophages (HLA-Dr+/CD66abce-) and neutrophils (HLA-Dr-/CD66abce+). IL-1ß, TNF-α and IL-6 production was investigated in these subpopulations. It was found that CD18-positive cells correlated significantly with POM. However, only in samples with POM below 10(6) per millilitre, FACS detected significantly higher leucocyte numbers. Moreover, in 31% of these samples, FACS leucocyte detection reached threshold values greater than 1 × 10(6)  ml(-1) , fulfilling the criteria for diagnosis of leucocytospermia. Neutrophils were the predominating leucocyte population. Nevertheless, in 24% of samples, macrophages encountered more than 50% of leucocytes. Most interestingly, only macrophages produced significant amounts of IL-1ß, TNF-α and IL-6. It is concluded that FACS improves detection and functional differentiation of seminal leucocytes as one of the diagnostic hallmarks of male genital tract inflammation.

Acute epididymitis in ultrasound: results of a prospective study with baseline and follow-up investigations in 134 patients.

OBJECTIVES: To perform a comprehensive follow-up analysis of ultrasonographic scrotal features and associated signs in patients with acute epididymitis. METHODS: Between 2007 and 2012, 134 adults (median age 54 years) with acute epididymitis underwent scrotal ultrasonography and palpation at first presentation and after 2 weeks and 3 months. RESULTS: At first presentation, 61 patients (45.5%) had hydrocele, 63 (47.0%) concomitant orchitis, and 8 (5.9%) epididymal abscess. Epididymitis was predominantly located in 24 cases (17.9%) in the head, 52 cases (38.8%) in the tail, and 58 cases (43.3%) in both. On the affected side, testicular volume was 16.9 ± 6.8 ml and peak systolic velocity of the testicular artery was 23.7 ± 7.5 cm/s, compared to the healthy side with 12.3 ± 4.4 ml and 9.5 ± 3.6 cm/s respectively (P<0.001). Concomitant orchitis was associated with hydrocele, testicular enlargement and pain (P<0.01). Orchiectomy due to secondary testicular infarction was necessary in four cases, while in all other patients ultrasound parameters normalized. Only 16/90 patients (17.8%) showed a persistent epididymal swelling after 3 months. CONCLUSIONS: Common ultrasound features include hydrocele, epididymal enlargement, hyperperfusion, and testicular involvement. Under conservative treatment, ultrasound parameters normalize without evidence of testicular atrophy even in patients with epididymal abscess or concomitant orchitis.

Male urogenital infections: impact of infection and inflammation on ejaculate parameters.

BACKGROUND: Urogenital infections and inflammation may contribute significantly to ejaculate parameters essential for male infertility. METHODS: For this review, data were acquired by a systematic search of the medical literature of the last 5 years. RESULTS: We address the andrological relevance of male urogenital infections and inflammation on ejaculate parameters. The different classification systems of the WHO and NIH are illustrated. In most cases, a separation of the different areas of the urogenital tract, for example, of the prostate, epididymis and testicles, is not possible. The significance of bacteriospermia with common bacteria is discussed. Furthermore, HIV, ascending chlamydial, mycoplasmal and gonococcal infections are relevant. Especially, the relevance of sexually transmitted microorganisms seems to be underestimated. Leukocytospermia is not well defined in its biological significance. Seminal plasma elastase and the cytokine expression reveal better insights into the inflammatory response of the seminal pathways. Sperm antibodies and reactive oxygen species are not usable as indicators for infection and inflammation. Different aspects for an impairment of ejaculate quality have been demonstrated although a direct ascension of microorganisms to the prostate has not been confirmed. Probably, lesions of the epididymis may sustain an ongoing disturbance of sperm parameters. A potential negative influence of urogenital infections and inflammation on sperm function is under discussion. However, the severity of impairment differs according to the underlying infections and the involved compartments. CONCLUSIONS: Signs of infections and inflammation in the ejaculate of infertile men are common, and the relevance is often doubtful in spite of microbiological, spermatological and immunological facilities.

Prostatitis and andrological implications.

AIM: The prostatitis syndrome is a frequent disease affecting men in their reproductive age. The prostatitis syndrome is classified according to the National Institutes of Health (NIH) definition. Andrological implications of the prostatitis syndrome might encompass fertility issues, sexual dysfunctions and endocrinological alterations and influences. METHODS: A medline query using the terms prostatitis AND andrological implication, fertility, sexual dysfunction or endocrinology was performed. RESULTS: Acute bacterial prostatitis and andrological implications have not been adequately addressed. Patients with chronic bacterial prostatitis and chronic pelvic pain syndrome have been investigated evaluating sperm parameters. Some studies showed impaired sperm parameters. In chronic bacterial prostatitis, half of the patients reveal significant bacteriospermia with still debatable deleterious effects on sperm quality. Few interventional studies have addressed fertility issues in those patients. Anti-inflammatory treatment perhaps could have a positive impact on sperm parameters. Sexual dysfunction can be described by different components such as erectile, ejaculatory, orgasmic and sexual desire dysfunctions. Sexual dysfunction in chronic prostatitis adds to the number of positive symptom phenotypes and correlates therefore with increasing symptom scores in patients with chronic prostatitis syndromes. However, prospective interventional studies on the role of sexual dysfunctions are missing. Hormones have been found to modulate the inflammatory response via different receptors, particularly via estrogen receptor alpha. This evidence, however, is mainly limited to pre-clinical studies currently. CONCLUSION: Andrological implications are heterogenous and frequently described in patients with chronic prostatitis syndrome. Nonetheless, andrological factors have not been routinely addressed as primary variables in the different studies, which makes further research necessary.

[Seminal cytokines: is quantification useful in urogenital disorders?]. / Zytokine im Ejakulat : Ist die Bestimmung bei urogenitalen Erkrankungen sinnvoll?

Cytokines are cellular messengers which play a key role in many biological conditions such as immune defence and reproduction. During recent years analysis of seminal cytokines has become of increasing interest in various pathologies. To evaluate the current role of seminal cytokines we performed a systematic literature search within the framework of our focus group "Male Infertility during Infection and Inflammation - MIBIE". Out of 581 manuscripts we identified 124 original articles which investigated a total of 31 different cytokines. These studies can be categorized according to the following three topics: infertility, infections and chronic prostatitis. The current analysis demonstrates that seminal cytokine profiles are not associated with either semen quality or fertility; however, cytokines might be beneficial for diagnosis and monitoring therapy in patients with urogenital infections/inflammation. Further studies are needed to clarify if a single cytokine or a combination of different cytokines is necessary to evaluate different pathologies.