RESUMO
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.
Assuntos
Varicocele/imunologia , Animais , Modelos Animais de Doenças , Humanos , Inflamassomos , Masculino , Ratos , TestículoRESUMO
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.
Assuntos
Fumar Cigarros/efeitos adversos , Infertilidade Masculina/imunologia , Sêmen/química , Proteínas de Plasma Seminal/análise , Varicocele/complicações , Acrossomo/efeitos dos fármacos , Acrossomo/imunologia , Acrossomo/patologia , Adulto , Brasil , Estudos Transversais , Fragmentação do DNA/efeitos dos fármacos , Epididimo/irrigação sanguínea , Epididimo/efeitos dos fármacos , Epididimo/imunologia , Humanos , Infertilidade Masculina/patologia , Masculino , Pessoa de Meia-Idade , não Fumantes/estatística & dados numéricos , Proteômica/estatística & dados numéricos , Sêmen/imunologia , Sêmen/metabolismo , Análise do Sêmen/estatística & dados numéricos , Proteínas de Plasma Seminal/metabolismo , Transdução de Sinais/imunologia , Fumantes/estatística & dados numéricos , Testículo/irrigação sanguínea , Testículo/efeitos dos fármacos , Testículo/imunologia , Nicotiana/toxicidade , Varicocele/imunologia , Adulto JovemRESUMO
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.
Assuntos
Proteínas e Peptídeos Salivares/metabolismo , Sêmen/metabolismo , Proteínas de Plasma Seminal/metabolismo , Varicocele/patologia , Varicocele/cirurgia , Humanos , Infertilidade Masculina/patologia , Infertilidade Masculina/cirurgia , Inflamação/patologia , Masculino , Proteínas e Peptídeos Salivares/genética , Análise do Sêmen , Proteínas de Plasma Seminal/genética , Varicocele/imunologiaRESUMO
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.
Assuntos
Infertilidade Masculina/imunologia , Leucócitos , Sêmen/citologia , Varicocele/imunologia , Adulto , Humanos , Infertilidade Masculina/complicações , Infertilidade Masculina/metabolismo , Peroxidação de Lipídeos , Masculino , Varicocele/complicações , Varicocele/metabolismoRESUMO
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.
Assuntos
Autoanticorpos/análise , Espermatozoides/imunologia , Espermatozoides/fisiologia , Varicocele/imunologia , Varicocele/fisiopatologia , Adolescente , Adulto , Humanos , MasculinoRESUMO
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