Characterization of varicocele-induced animal models: Potential role of inflammasome complex in the varicocele pathophysiology.

Varicocele mechanisms and its impact in testicular dysfunction has been studied in order to understand the pathophysiology involved in this disease. However, study designs using testicular tissues from varicocele patients are restricted due to ethical limitations. Therefore, the use of animal models, mainly rats, that mimics varicocele and its effects is an option to develop new approaches. The surgical technique, that induces the varicocele in rats, is based on the partial obstruction of the left renal vein, leading to a dilation in the left spermatic vein and consequently to the pampiniform plexus, resulting in varicocele-induced condition. Thus, the study of the cellular and molecular mechanisms involved in varicocele development can be addressed in depth. Besides the animal model goal to uncover the exact varicocele pathophysiology, varicocele induced models are the best options to develop new non-surgical and less invasive therapies. Various animal model studies designed and investigated antioxidant and anti-inflammatory agents to face varicocele conditions. Minding this fact, we tried to discuss a newly uncovered complex in varicocele condition, known as inflammasome complex. Taking into consideration the possible inflammatory state present in varicocele, the inflammasome complex has been proposed to be involved in the pathophysiology of this disease.

Varicocele-Mediated Male Infertility: From the Perspective of Testicular Immunity and Inflammation.

Background: Varicocele (VC) is present in 35 - 40% of men with infertility. However, current surgical and antioxidant treatments are not completely effective. In addition to oxidative stress, it is likely that other factors such as testicular immune microenvironment disorder contribute to irreversible testicular. Evidence suggests that VC is associated with anti-sperm antibodies (ASAs), spermatogenesis and testosterone secretion abnormalities, and testicular cytokine production. Moreover, inhibition of inflammation can alleviate VC-mediated pathogenesis. The normal function of the testis depends on its immune tolerance mechanism. Testicular immune regulation is complex, and many infectious or non-infectious diseases may damage this precision system. Results: The testicular immune microenvironment is composed of common immune cells and other cells involved in testicular immunity. The former includes testicular macrophages, T cells, dendritic cells (DCs), and mast cells, whereas the latter include Leydig cells and Sertoli cells (SCs). In animal models and in patients with VC, most studies have revealed an abnormal increase in the levels of ASAs and pro-inflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha in the seminal plasma, testicular tissue, and even peripheral blood. It is also involved in the activation of potential inflammatory pathways, such as the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing (NLRP)-3 pathway. Finally, the development of VC-mediated infertility (VMI) may be facilitated by abnormal permeability of proteins, such as claudin-11, that constitute the blood-testis barrier (BTB). Conclusions: The testicular immune response, including the production of ASAs and inflammatory factors, activation of inflammatory pathways, and destruction of the BTB may be involved in the pathogenesis of VMI it is necessary to further explore how patient outcomes can be improved through immunotherapy.

Evaluation of seminal fluid leukocyte subpopulations in patients with varicocele.

Varicocele is a common cause of sperm damage. Some studies showed higher concentration of seminal leukocytes in patients with varicocele. The aim of the study was to evaluate seminal leukocyte subpopulations in patients with varicocele. We enrolled 20 patients with varicocele and 20 age-matched healthy men. Sperm analysis was conducted according to the World Health Organization (WHO) 2010 criteria. We evaluated seminal leukocyte subpopulations and bio-functional sperm parameters by flow cytometry. Patients with varicocele had significantly lower sperm concentration and total number than controls. Regarding seminal leukocyte subpopulations, patients with varicocele had a significantly lower percentage of CD8+ and CD16+ leukocytes and a significantly higher percentage of CD4+ leukocytes than controls. As for bio-functional sperm parameters, we found that patients with varicocele had a significantly lower percentage of alive spermatozoa compared to the control group. These results may explain the increased level of cytokines in the seminal plasma of patients with varicocele.

Seminal plasma protein networks and enriched functions in varicocele: Effect of smoking.

To verify a possible synergistic effect of smoking and varicocele on the seminal plasma proteome and biological functions, a cross-sectional study was performed in 25 smokers and 24 nonsmokers. Samples were used for conventional semen analysis, functional analysis (DNA fragmentation, acrosome integrity and mitochondrial activity) and proteomics by a shotgun approach. Functional enrichment of biological pathways was performed in differentially expressed proteins. Smokers presented lower ejaculate volume (p = .027), percentage of progressively motile spermatozoa (p = .002), total sperm count (p = .039), morphology (p = .001) and higher percentage of immotile spermatozoa (p = .03), round cell (p = .045) and neutrophil count (p = .009). Smokers also presented lower mitochondrial activity and acrosome integrity and higher DNA fragmentation. We identified and quantified 421 proteins in seminal plasma, of which one was exclusive, 21 were overexpressed and 70 were underexpressed in the seminal plasma of smokers. The proteins neprilysin, beta-defensin 106A and histone H4A were capable of predicting the smoker group. Enriched functions were related to immune function and sperm machinery in testis/epididymis. Based on our findings, we can conclude that cigarette smoking leads to the establishment of inflammatory protein pathways in the testis/epididymis in the presence of varicocele that seems to act in synergy with the toxic components of the cigarette.

Stem Cell Factor Receptor Immunoexpression in Adolescent Varicocele.

PURPOSE: Stem cell factor receptor (c-kit) plays a crucial role in regulating proliferation and survival of germ cells. The aim of this study was to find the correlation between the number of c-kit positive germ cells, testicular asymmetry and histological grade in varicocele affected testis samples of adolescents. MATERIALS AND METHODS: Twenty testicular biopsy samples of adolescents affected by varicocele and eight normal control testes were included. The relationship between percentage of testicular asymmetry, number of tubular c-kit positive germ cells and severity of spermatogenic failure was assessed. RESULTS: The mean (SD; median) histological grade for spermatogenic failure in controls was 1.37(0.52; 1), while in the varicocele group, it was 2.70(1.08; 3) (P = .0052). Mean(SD; median) number c-kit positive germ cells in the control group were 20.1(2.52; 20), while in the varicocele group it was 12.35(7.16; 12.5) (P = .0059). Spearman test documented a significant positive correlation between percentage of hypotrophy and histological grade of spermatogenic failure (r = 0.5544 , 95% CI: 0.1345 to 0.8055, P = .0112) but a negative correlation with the number of c-kit positive cells (r = - 0.5871, 95% CI: - 0.8219 to -0.1817, P = .0065). Moreover, a significant negative correlation was found between grade of histological changes and number of c-kit positive germ cells (P < .0001). CONCLUSION: A significant correlation between hypotrophy, histological lesions and c-kit positive germ cells exists in varicocele testes. This finding suggests a possible role for c-kit in the pathogenesis of germ cell impairment in varicocele. Histological changes and lack of c-kit germ cells were also noted in testes not displaying hypotrophy. We believe that reliable markers should be found as better predictors of testicular function in adolescent with varicocele.

Cysteine-rich secretory protein 3: inflammation role in adult varicocoele.

BACKGROUND: Cysteine-rich secretory protein (CRISP-3), a protein involved in inflammatory response, is highly increased in seminal plasma of adolescents with varicocoele and altered semen analysis, but not in adolescents with varicocoele and normal semen. It is not known, however, whether this increased seminal concentration occurs as an acute marker during the initial stages of varicocoele or whether this persists as an altered protein pathway. OBJECTIVE: The purpose of this study, thus, was to test the hypothesis that this inflammatory state persists through adulthood and the correction of varicocoele could correct this state, by identifying the levels of CRISP-3 in seminal plasma. MATERIALS AND METHODS: This study was carried out in two substudies: (i) to verify the effect of varicocoele and (ii) to verify the effect of varicocelectomy on seminal plasma CRISP-3 levels. Seminal plasma CRISP-3 levels (29 and 31 kDa isoforms) were assessed for each provided sample using standard Western blotting. RESULTS: The varicocoele group presented higher seminal levels of CRISP-3 when compared to controls, with a 67.5-fold increase in the unglycosylated isoform (29 kDa) and a 5.2-fold increase in the glycosylated isoform (31 kDa). In contrast, CRISP-3 levels decreased following varicocelectomy, both in the unglycosylated (5.6-fold decrease) and in the glycosylated (4.3-fold decrease) isoforms. DISCUSSION: CRISP-3, a protein involved in inflammation, is increased in seminal plasma of men with varicocoele and this is partially reversed by varicocelectomy. Monitoring its seminal levels may be useful for assessing inflammation-related alterations to fertility in men with varicocoele. CONCLUSION: We conclude that, in the presence of varicocoele, there is a marked increase in seminal CRISP-3 levels. Surgical intervention (varicocelectomy) decreases CRISP-3 levels and improves semen quality.

Cytokines in the male reproductive tract and their role in infertility disorders.

Cell integration between the immune and reproductive systems is the basis for normal male reproductive physiology. Cytokines are a part of the autocrine/paracrine network operating in the male reproductive tract. At the same time, immunological reactions occurring via cytokines appear to be both beneficial and/or risk factors for male fertility. As the cytokines are produced by a whole spectrum of cells in all compartments of the male genital tract, they can also be involved in a variety of andrological disorders. The monitoring of cytokines and other immune factors in seminal plasma may offer a chance to better understand the mechanisms leading to sub-/infertility. In this review, we present insights into cytokine interplay in some of the pathological conditions associated with male reproduction.

Male fertility and varicocoele: role of immune factors.

The role of antisperm antibodies (ASA) in the aetiopathogenesis of varicocoele-related male infertility remains unclear. The objective of this study was to determine whether varicocoele is associated with antisperm immune response and whether this factor provides additional affect on male fertility. We performed a multicentral, prospective study that included the clinical examination of 1639 male subjects from infertile couples and 90 fertile men, the evaluation of the absolute and relative risks of immune infertility associated with varicocoele and the impact of the autoimmune response on the semen quality. The methods used were as follows: standard examination of seminal fluid according to WHO criteria; ASA detection in seminal fluid using mixed antiglobulin reaction (MAR) and direct flow cytometry; measurement of spontaneous and ionophore-induced acrosome reactions; oxidative stress evaluation with luminal-dependent chemiluminescence method and evaluation of DNA fragmentation by sperm chromatin dispersion. The prevalence of varicocoele-related immune infertility is about 15% and does not depend on the grade of vein dilatation both in primary and secondary fertility disorders. Varicocoele is not an immediate cause of autoimmune reactions against spermatozoa, but is a cofactor increasing ASA risk; the OR of immune infertility after a testicular trauma in varicocoele patients increases twofold. In varicocoele patients, the autoimmune antisperm reaction is accompanied by a more significant decrease in the semen quality (concentration and number of progressively motile and morphologically normal spermatozoa in the ejaculate), acrosome reaction disorders (presence of pre-term spontaneous and lack of induced reactions) and an increase in the proportion of spermatozoa with DNA fragmentation. These disorders correlate with the level of sperm oxidative stress; reactive oxygen species (ROS) production in ASA-positive varicocoele patients is 2.8 and 3.5 times higher than in ASA-negative varicocoele patients and fertile men respectively. We did not find correlation between the grade of spermatic cord vein dilatation and ROS production.

Semen characteristics and inflammatory mediators in infertile men with different clinical diagnoses.

This study was aimed at investigating whether semen characteristics in different clinical diagnoses of infertility are associated with PMN elastase, IL-6, IL-8, IL-1beta and TNFalpha levels detected in seminal plasma. Sixty-eight patients were divided into groups according to their clinical diagnosis: idiopathic infertility (group I), varicocele with infections (group II), varicocele (group III), infections (group IV), controls (group V). Physical examination and scrotal Eco-color Doppler was used to detect the varicocele. Patients with positive bacteriological semen analysis were considered as having an infection of the male reproductive tract. Samples were examined by light microscopy and transmission electron microscopy (TEM). TEM data were quantified with a mathematical formula furnishing a fertility index and the percentage of sperm apoptosis, immaturity and necrosis. PMN elastase/alpha1-PI complex levels were determined by ELISA and IL-6, IL-8, IL-1beta, TNFalpha by Bio-Plex Cytokine assay. Sperm concentration (I-II: p < 0.005; III-IV: p < 0.0001), motility (I-IV: p < 0.0001) and the fertility index (I: p < 0.005; II-IV: p < 0.0001) were significantly lower in the groups vs. controls, whereas sperm pathologies, except for apoptosis, were significantly higher in group I and apoptosis and necrosis were higher in group III. An increase in immaturity (p < 0.005) with a decrease in necrosis (p < 0.005) were observed in group III vs. group IV. Significantly higher levels of inflammatory mediators were detected in groups III and IV vs. controls. Despite a broad relationship among different inflammatory mediators, no correlation was found among them and the semen parameters, including indices from TEM analysis. In conclusion, patients with idiopathic infertility showed altered semen quality and normal levels of inflammatory mediators. Genitourinary infection and varicocele induced an inflammatory effect which could play a detrimental role in spermatogenesis, revealed by a decrease in sperm motility and the fertility index, concomitant with an increase in immaturity mainly in varicocele and necrosis in infection.

Increased IL-18 levels in seminal plasma of infertile men with genital tract infections.

PROBLEM: Interleukin (IL)-18 is a novel cytokine, previously known as interferon (IFN)-gamma inducing factor. We evaluated the levels of IL-18 and IFN-gamma in seminal plasma (SP) of fertile and infertile men. METHOD OF STUDY: Semen samples were obtained by masturbation from 80 men, and were examined for the levels of IL-18 and IFN-gamma by enzyme-linked immunosorbent assay. Seven groups were included: (i) fertile men (n = 18), (i) infertile men with genital tract infections (n = 17), (iii) with varicocele (n = 15), (iv) with Klinefelter syndrome (n = 6), (v) with cryptorchidism (n = 7), (vi) with mumps orchitis (n = 7), and (vii) with idiopathic testicular lesions (n = 10). RESULTS: Mean levels of IL-18 were higher in SP from infertile men with genital tract infections compared with SP from other groups except Klinefelter syndrome (P < 0.05). However, no significant differences could be detected for IFN-gamma. A significant positive correlations was found between IL-18 and IFN-gamma in total patient population (P < 0.001). Moreover, a negative correlation was observed between IL-18 and sperm concentrations, and motility (P < 0.01 and < 0.03, respectively). Furthermore, there was a positive and statistically significant association between IL-18 and IFN-gamma levels in SP of infertile men with genital tract infections (P < 0.0001). However, there was no relationship between IL-18 and IFN-gamma, and semen parameters in the same group. CONCLUSION: SP IL-18 levels were increased in men with urogenital infections. Thus, the elevated expression of IL-18 in SP may be used as a diagnostic marker in the male genital tract infections.

Varicocele and antisperm antibody: fact or fiction?

OBJECTIVE: To study the level of antisperm antibodies (ASAB) in the serum and semen of infertile men with varicocele before and 6 months after varicocelectomy. MATERIALS AND METHODS: We performed a prospective study of 81 infertile men undergoing microsurgical inguinal varicocelectomy. Female factor was excluded. Semen analysis and seminal and serum ASAB (direct and indirect IgG and IgA), as measured by SpermMar test, were performed before and after surgery at 6 months. A control group consisting of idiopathic infertile patients was evaluated for ASAB. RESULTS: Eighty-one patients with a mean age of 28.7 years (23 to 42) completed our study. Mean sperm count, motility, and abnormal forms were improved after surgery and were statistically significant for sperm density and morphology (P < 0.05). Before surgery, 21 patients (26%) had a low positivity for ASAB (10 to 40%). Six months after surgery, the ASAB titer was reduced in 15 (A group), increased in 3 (B group), and reduced in another 3 (C group). The C group also had an increase in other titers. In the A group sperm count, motility and normal forms improved after surgery (P < 0.05). In the B group, motility was reduced after surgery. In the C group, motility and normal forms were reduced after surgery. Sixty patients were negative for ASAB before surgery. Of these, 48 showed an increase in at least one of the ASAB types to some degree that had no significant effect on semen parameters. In the control group, two patients (7%) were weakly positive for ASAB. CONCLUSIONS: Varicocelectomy may reduce the ASAB level, and this reduction has a good effect on semen parameter quality. Also, it may raise the ASAB level in some patients. This positive conversion has no adverse effect on semen parameters.

[The effect of seminal leukocytes on semen quality in subfertile males with and without varicocele]. / Efectos de la leucocitospermia sobre la calidad seminal en varones subfértiles con y sin varicocele.

OBJECTIVES: To compare the concentration of leukocytes and round cells in semen samples of subfertile males (SM), men with varicocele (VM), and fertile males (FM) to establish a possible relationship between leukocyte concentration, semen parameters (pH, concentration, mobility, spermatic morphology) and lipidic peroxidation of the spermatozoid. METHODS: We evaluated 298 semen samples from: 42 fertile males, 170 subfertile males, and 86 men with varicocele. Sperm tests were performed following WHO criteria. All samples with leukocyte counts higher than 1 million/ml were submitted for oxidative stress study (malonyldialdehyde in seminal plasma). RESULTS: Leukocyte concentration was higher in subfertile males and men with varicocele (2.5 +/- 2.1 x 10(6)/ml and 2.3 +/- 2.1 x 10(6)/ml) than in fertile males (1.1 +/- 0.1 x 10(6)/ml) (p 0.0001). In the same way concentration of round cells was higher in the SM group (6.5 +/- 0.3 x 10(6)/ml) and VM group (6.1 +/- 0.4 x 10(6)/ml) than in FM (4.5 +/- 0.4 x 10(6)/ml) (p 0.05). Spermatozoid concentration was lower in SM (42.1 +/- 2.4 x 10(6)/ml) and VM (9.9 +/- 3.5 x 10(6)/ml) than in FM (82.4 +/- 5.7 x 10(6)/ml) (p 0.0001). The percentage of spermatozoa with type "a" mobility was lower in the SM (14.1 +/- 0.9) and VM (19.9 +/- 1.4) groups than in the FM group (50.0 +/- 1.3) (p 0.0001). In the same way, "a + b" mobility was lower in the SF group (26.7 +/- 1.4) and VM group (34.1 +/- 1.9) than in the FM group (50.0 +/- 1.3) (p 0.0001). The SM group showed a lower percentage of normal forms (43.3 +/- 1.5) than the VM (50.0 +/- 1.6) and FM (60.6 +/- 1.3) groups (p 0.0001). When grouping by concentration of peroxidase positive cells, there were not statistical differences in the spermatic variables in SM, with the exception of progeny cells. Type "a" mobility in the VM group was lower in the peroxidase positive group than in the peroxidase negative group (p 0.005); "a + b" mobility was also lower in the peroxidase positive men than in peroxidase negative (p 0.01); in the progeny cells they were higher in the peroxidase positive males (4.2 +/- 0.4 x 10(6)/ml) than in peroxidase negative males (3.0 +/- 0.3 x 10(6)/ml). Malonyldialdehyde concentrations were significantly higher in seminal plasma of subfertile and varicocele males than in fertile males (p 0.006, and p 0.03). CONCLUSIONS: Increased number of semen lymphocytes is more frequent in subfertile and varicocele males than in fertile males. The increase of semen leukocytes is associated with deterioration of seminal parameters. Oxidative stress has a negative influence on seminal parameters in subfertile males of unknown etiology.

[Immunology and deterioration of seminal parameters in varicocele]. / Inmunología y deterioro de parámetros seminales en varicocele.

OBJECTIVE: To investigate the occurrence of antisperm antibodies (ASAs) and their correlation to semen parameters in varicocele patients. METHODS: Semen samples from 137 patients with unilateral palpable clinical varicocele aged 15-35 years who consulted at the Infertility and Urology services of the Provincial del Centenario and Eva Peron teaching hospitals in Rosario (Argentina) were collected and analyzed according to the WHO standardized protocols and ASAs were tested with TAC II. Statistical analyses were performed using log linear models. RESULTS: Motility was impaired in 67.2% (p < 0.001) and morphology in 97.1%. Sperm concentration decreased in 19.7%, although it was not statistically different from that of the normal population. Of the infertile population with varicocele, 46.7% had positive ASAs with TAC II. CONCLUSIONS: We found a statistically significant correlation only between motility and sperm count (p < 0.01). Our study indicates that the severe dysspermia observed may be caused by autoimmune processes that trigger cellular and humoral mechanisms.

A comparison of the sperm mixed-agglutination reaction test with the peroxidase-labelled protein A test for detecting antisperm antibodies in infertile men with varicocele.

OBJECTIVE: To compare the sperm mixed-agglutination reaction (sMAR) with the peroxidase-labelled protein A method (POPA) in infertile patients with varicocele. PATIENTS, SUBJECTS AND METHODS: The study comprised 30 men with a history of varicocele-associated infertility and 30 fertile men (control group). Antisperm antibodies against spermatozoa in the semen and against progenitor spermatozoa in testicular tissue were detected using the two methods. RESULTS: The tests were positive in 15 (50%) of patients with both the sMAR and the POPA methods, while no autoantibodies were detected in the control group. There were no significant differences between the methods. The sensitivity and specificity of both tests was approximately 93%, with no significant difference between them (P>0. 05). CONCLUSION: Both methods may be used for detecting sperm autoantibodies in infertile patients with varicocele.

Utilidad del test de LHRH en el varicocele / Utility of the LHRH test in the varicocele

El test de estimulación con GNRH ha sido ampliamente utilizado intentando predecir de resultados quirúrgicos y en evaluación de función testicular y espermatogénica. El objetivo de este trabajo es observar los patrones y de respuesta al test de GNRH, en grupos de enfermos de distintas edades, portadores de varicocele y comparar sus resultados con un grupo control. Se realizó un estudio comparativo en el que se incluyó a 152 pacientes portadores de varicocele y un grupo control de 22 individuos sanos sin patología testicular, que fueron sometido a un test de estimulación con GNRH. El test fue realizado en condiciones de reposo con la inyección de 100 ug de LHRH, con medición de LH y FSH basases, a los 15.30 y 45 min. La medición se realizó con técnica de radioinmuno análisis. Los valores promedios de cada grupo posterior a la estimulación con GNRGH no mostró diferencias significativas entre los tres grupos. Sin embargo existe un 22 por ciento de los adolescentes con una curva alterada para LH y un 34 por ciento de adultos que presentaba una curva alterada con valores superiores a los del grupo control. Un 20 por ciento de los adolescentes tuvieron una curva de FSH con valores sobre el esperado (percentil 95). En los adultos un 32 por ciento presentaba una curva de respuesta anormal, con valores elevados. Un patrón de respuesta anormal al test de GNRH es el resultado de la injuria testicular primaria sobre la célula de Leydig (LH) y anormalidad de los túbulos seminíferos (FSH), sin embargo esta respuesta anormal no es condición obligatoria del varicocele, así observamos que entre un 20 a 32 por ciento de enfermos con varicocele presenta esta respuesta alterada y es tal vez este el grupo de enfermos que se beneficiaría de la cirugía correctora del varicocele. No se puede asegurar que los adolescentes con varicocele y con un test de LHRH alterado serán infértiles pero razonablemente debiera corregirse esta anormalidad mediante cirugía. Por lo tanto con un test anormal se debe operar. El seguimiento de estos pacientes dará información futura importante

Evaluation of beta-endorphin and interleukin-6 in seminal plasma of patients with certain andrological diseases.

Human semen contains large amounts of opioid peptides and cytokines. We have measured the concentrations of interleukin (IL)-6 in 140 semen samples and of beta-endorphin in 77 semen samples. The median concentration of beta-endorphin in seminal plasma from normozoospermic men (n = 23) was 154.7 pg/ml (10th-90th percentiles, 42.0-774.6), and there was no significant difference in the beta-endorphin concentration among normozoospermic, oligozoospermic (n = 28), asthenozoospermic (n = 15), azoospermic (n = 4) and post-vasectomy (n = 7) samples. There was no correlation between beta-endorphin concentration and sperm characteristics, nor with blood hormones. beta-Endorphin concentration was lower in cases with immunological infertility, as revealed by a positive direct mixed antiglobulin reaction test (n = 12) (P < 0.01), than in matched controls. The median concentration of IL-6 in samples with normal sperm concentration, motility and morphology with or without white blood cells (n = 39) was 26.1 pg/ml (10th-90th percentiles, 7.3-172.3), and there was no significant difference in the IL-6 concentration among normozoospermic, oligozoospermic (n = 46), asthenozoospermic (n = 32), azoospermic (n = 13) and post-vasectomy (n = 10) samples. The IL-6 concentration was significantly higher in cases of varicocele (n = 22) without white blood cells in semen (P < 0.001) than in matched controls without varicocele (n = 23). In addition, the IL-6 concentration was elevated (P < 0.0001) in cases with accessory sex gland inflammation (n = 40). IL-6 concentration was positively correlated with white blood cells in semen (n = 60, r = 0.59, P < 0.0001), but there was no correlation with beta-endorphin concentration. The IL-6 concentration chosen to differentiate between cases with and without accessory gland inflammation was 45.3 pg/ml, with a specificity of 80.6% and a sensitivity of 92.5%. It is concluded that beta-endorphin in seminal plasma plays an immune suppressive role, and that increased IL-6 concentration may be related to testicular dysfunction in cases with varicocele. Furthermore, IL-6 is an accurate marker of accessory sex gland inflammation.

Antispermatozoal antibody values after varicocelectomy.

Although there are many causes of the production of antispermatozoal antibodies, there are still unknown aetiological factors. Antispermatozoal antibodies were investigated in the postoperative period in 25 infertile men with varicocele whose antispermatozoal antibody tests were negative in the preoperative period. Antispermatozoal antibodies were found in the serum in 4 of the 25 (16%) infertile men after varicocele operation. Postoperative genital infections were detected in 6 patients and antispermatozoal antibodies were present in only 2 of them. The correlation between these antibodies and varicocele has been demonstrated but there is no report on the association of antibodies with varicocelectomy in the literature to date.