RESUMO
Varicocele can reduce male fertility potential through various oxidative stress mechanisms. Excessive production of reactive oxygen species may overwhelm the sperm's defenses against oxidative stress, damaging the sperm chromatin. Sperm DNA fragmentation, in the form of DNA strand breaks, is recognized as a consequence of the oxidative stress cascade and is commonly found in the ejaculates of men with varicocele and fertility issues. This paper reviews the current knowledge regarding the association between varicocele, oxidative stress, sperm DNA fragmentation, and male infertility, and examines the role of varicocele repair in alleviating oxidative-sperm DNA fragmentation in these patients. Additionally, we highlight areas for further research to address knowledge gaps relevant to clinical practice.
Assuntos
Fragmentação do DNA , Infertilidade Masculina , Estresse Oxidativo , Espermatozoides , Varicocele , Humanos , Masculino , Varicocele/fisiopatologia , Varicocele/complicações , Estresse Oxidativo/fisiologia , Infertilidade Masculina/etiologia , Infertilidade Masculina/genética , Infertilidade Masculina/fisiopatologia , Infertilidade Masculina/metabolismo , Espermatozoides/fisiologia , Espermatozoides/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
PURPOSE: Varicocele is a condition known to cause damage to seminal parameters and sperm function. Furthermore, it has been hypothesized that the varicocele effect on fertility is time-dependent; however, little is known about the consequences of its establishment time on reproductive organs and/or sperm function. This study aimed to evaluate the effect of the duration of experimental varicocele on reproductive organs, sperm parameters, and sperm function. MATERIALS AND METHODS: Varicocele induction surgeries were performed in Wistar rats aged 40 or 100 days old. At 160-day-old, analyses were performed, including biometry of reproductive organs (prostate, seminal vesicles, epididymis, and testis), sperm parameters (vitality, morphology, and motility), and sperm function tests (nuclear DNA integrity, acrosome integrity, and mitochondrial activity). RESULTS: The analysis of the biometry of reproductive organs showed no differences between distinct ages in which varicocele was induced. The total abnormal sperm morphology was bigger in animals with varicocele induced to 100 days old than in animals with varicocele induced to 40 days old. Regarding nuclear DNA integrity, animals of varicocele induced to 100 days old showed worse results compared to animals of varicocele induced to 40 days old. Other parameters analyzed showed no differences between varicocele groups. CONCLUSION: In this study conducted on rats, we conclude that varicocele adversely affects sperm, particularly its function. However, we did not observe a negative progressive effect on sperm.
Assuntos
Ratos Wistar , Análise do Sêmen , Motilidade dos Espermatozoides , Espermatozoides , Varicocele , Animais , Masculino , Varicocele/fisiopatologia , Varicocele/patologia , Espermatozoides/fisiologia , Motilidade dos Espermatozoides/fisiologia , Fatores de Tempo , Modelos Animais de Doenças , Testículo/patologia , Ratos , Fatores Etários , Epididimo/patologiaRESUMO
OBJECTIVE: To evaluate the effect of varicocelectomy on sperm deoxyribonucleic acid fragmentation (SDF) rates in infertile men with clinical varicocele. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Infertile men with clinical varicocele subjected to varicocelectomy. INTERVENTION(S): Systematic search using PubMed/Medline, EMBASE, Cochrane's central database, Scielo, and Google Scholar to identify relevant studies published from inception until January 2021. We included studies comparing SDF rates before and after varicocelectomy in infertile men with clinical varicocele. MAIN OUTCOME MEASURE(S): The primary outcome was the difference between the SDF rates before and after varicocelectomy. A meta-analysis of weighted data using random-effects models was performed. Results were reported as weighted mean differences (WMD) with 95% confidence intervals (CIs). Subgroup analyses were performed on the basis of the SDF assay, varicocelectomy technique, preoperative SDF levels, varicocele grade, follow-up time, and study design. RESULT(S): Nineteen studies involving 1,070 patients provided SDF data. Varicocelectomy was associated with reduced postoperative SDF rates (WMD -7.23%; 95% CI: -8.86 to -5.59; I2 = 91%). The treatment effect size was moderate (Cohen's d = 0.68; 95% CI: 0.77 to 0.60). The pooled results were consistent for studies using sperm chromatin structure assay, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, sperm chromatin dispersion test, and microsurgical varicocele repair. Subgroup analyses showed that the treatment effect was more pronounced in men with elevated vs. normal preoperative SDF levels, but the impact of varicocele grade remained equivocal. Meta-regression analysis demonstrated that SDF decreased after varicocelectomy as a function of preoperative SDF levels (coefficient: 0.23; 95% CI: 0.07 to 0.39). CONCLUSION(S): We concluded that pooled results from studies including infertile men with clinical varicocele indicated that varicocelectomy reduced the SDF rates. The treatment effect was greater in men with elevated (vs. normal) preoperative SDF levels. Further research is required to determine the full clinical implications of SDF reduction for these men.
Assuntos
Fragmentação do DNA , Fertilidade , Infertilidade Masculina/cirurgia , Espermatozoides/patologia , Procedimentos Cirúrgicos Urológicos Masculinos , Varicocele/cirurgia , Adulto , Humanos , Infertilidade Masculina/etiologia , Infertilidade Masculina/patologia , Infertilidade Masculina/fisiopatologia , Masculino , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos Masculinos/efeitos adversos , Varicocele/complicações , Varicocele/patologia , Varicocele/fisiopatologiaRESUMO
OBJECTIVE: To study the global DNA methylation pattern in spermatozoa of patients with varicocele as well as investigate their semen quality. DESIGN: Prospective observational case-control study. SETTING: University-affiliated hospital. PATIENT(S): A total of 26 men with varicocele and 26 fertile men without the disorder. INTERVENTIONS: Analysis of semen quality and sperm DNA methylation patterns. MAIN OUTCOME MEASURE(S): Semen quality evaluated by semen analysis, and sperm DNA methylation patterns investigated using the Infinium MethylationEPIC BeadChip platform. RESULT(S): Men with varicocele displayed decreased semen quality. The sperm DNA methylation analysis showed that men with varicocele exhibit global hypomethylation in comparison with the control group. A total of 59 differentially methylated CpG sites were identified, most of them hypomethylated in the varicocele group. In regional analyses, 1,695 DNA regions were differentially methylated in men with varicocele. These regions show associations with gamete generation, meiotic and meiosis cell cycle, and semen quality based on gene ontology analysis. CONCLUSION(S): Gene ontology results suggest that changes in methylation may be associated with the low semen quality phenotype observed in some varicocele patients because the observed differentially methylated regions in varicocele patients are related to male reproductive pathways. Additionally, the varicocele grade may influence the magnitude of global sperm DNA methylation change. To our knowledge, this is the first report analyzing changes at a regional or CpG-specific level in men with varicocele.
Assuntos
Metilação de DNA/fisiologia , Análise do Sêmen/métodos , Espermatozoides/fisiologia , Varicocele/diagnóstico , Varicocele/genética , Adulto , Humanos , Masculino , Espermatozoides/citologia , Varicocele/fisiopatologiaRESUMO
ABSTRACT Introduction: We evaluated the relationship between total testicular volume (TTV) and testicular volume differential (TVD) in adolescent males with varicocele. Both low TTV and high TVD have been independently associated with higher incidences of infertility later in life, but a predictive relationship between TTV and TVD directly has yet to be described. Materials and Methods: We retrospectively analyzed a database of Tanner 5 boys ages 16-21 who presented with varicocele at a single institution between 2009 and 2017. All patients had a scrotal sonogram prior to surgical intervention. TTV and TVD were calculated for each individual and four non-exclusive groupings of patients were created for statistical analysis. We chose 30 cc as a cut off value for low TTV based on prior studies. Results: 209 patients met our inclusion criteria. Mean age was 18.3 years (16-21, SD 1.7) with a mean total testicular volume of 36 cc (13.5-78.2, SD 11.1). Cut off points of TVD of 20% and TTV of 30 cc were used to separate patients. There were 65 boys (31%) with TTV < 30 cc and 58 boys (28%) with TVD ≥ 20%. Among males with TTV < 30 cc, 23 (35%) had a TVD ≥ 20%. Among males with TTV ≥ 30 cc, 35 (24%) had a TVD ≥ 20%. The relationship between TVD and TTV was found to be non-significant (p > 0.05). Discussion: Adolescent varicoceles continue to pose a challenge to pediatric urologists. The dilemma of over-aggressive treatment has proven difficult to balance with the risk of infertility. We hoped that elucidating the relationship between TTV and TVD could be useful in identifying patients who are at greater risk for infertility while decreasing the need for more intrusive testing, such as semen analysis, in an adolescent population. We looked at the direct relationship between low TTV and high TVD. In our population, there was a non-significant relationship between TTV < 30 cc and TVD ≥ 20% (p > 0.05) indicating that in adolescents with varicocele, TTV and TVD are independent variables. Our study limitations include the inherent user dependent bias of ultrasound measurements and data collection at a single institution with high ethnic diversity, possibly not comparable to all patient populations. Conclusions: Low TTV (< 30 cc) itself is not predictive of high TVD (≥ 20%) in adolescent boys with varicocele, despite their reported independent associations with impaired fertility in other studies.
Assuntos
Humanos , Masculino , Adolescente , Adulto Jovem , Motilidade dos Espermatozoides/fisiologia , Testículo/patologia , Varicocele/patologia , Tamanho do Órgão , Testículo/fisiopatologia , Testículo/diagnóstico por imagem , Varicocele/fisiopatologia , Índice de Gravidade de Doença , Estudos Retrospectivos , Análise do SêmenRESUMO
INTRODUCTION: We evaluated the relationship between total testicular volume (TTV) and testicular volume differential (TVD) in adolescent males with varicocele. Both low TTV and high TVD have been independently associated with higher incidences of infertility later in life, but a predictive relationship between TTV and TVD directly has yet to be described. MATERIALS AND METHODS: We retrospectively analyzed a database of Tanner 5 boys ages 16-21 who presented with varicocele at a single institution between 2009 and 2017. All patients had a scrotal sonogram prior to surgical intervention. TTV and TVD were calculated for each individual and four non-exclusive groupings of patients were created for statistical analysis. We chose 30 cc as a cut off value for low TTV based on prior studies. RESULTS: 209 patients met our inclusion criteria. Mean age was 18.3 years (16-21, SD 1.7) with a mean total testicular volume of 36 cc (13.5-78.2, SD 11.1). Cut off points of TVD of 20% and TTV of 30 cc were used to separate patients. There were 65 boys (31%) with TTV < 30 cc and 58 boys (28%) with TVD ≥ 20%. Among males with TTV < 30 cc, 23 (35%) had a TVD ≥ 20%. Among males with TTV ≥ 30 cc, 35 (24%) had a TVD ≥ 20%. The relationship between TVD and TTV was found to be non-significant (p > 0.05). DISCUSSION: Adolescent varicoceles continue to pose a challenge to pediatric urologists. The dilemma of over-aggressive treatment has proven difficult to balance with the risk of infertility. We hoped that elucidating the relationship between TTV and TVD could be useful in identifying patients who are at greater risk for infertility while decreasing the need for more intrusive testing, such as semen analysis, in an adolescent population. We looked at the direct relationship between low TTV and high TVD. In our population, there was a non-significant relationship between TTV < 30 cc and TVD ≥ 20% (p > 0.05) indicating that in adolescents with varicocele, TTV and TVD are independent variables. Our study limitations include the inherent user dependent bias of ultrasound measurements and data collection at a single institution with high ethnic diversity, possibly not comparable to all patient populations. CONCLUSIONS: Low TTV (< 30 cc) itself is not predictive of high TVD (≥ 20%) in adolescent boys with varicocele, despite their reported independent associations with impaired fertility in other studies.
Assuntos
Motilidade dos Espermatozoides/fisiologia , Testículo/patologia , Varicocele/patologia , Adolescente , Humanos , Masculino , Tamanho do Órgão , Estudos Retrospectivos , Análise do Sêmen , Índice de Gravidade de Doença , Testículo/diagnóstico por imagem , Testículo/fisiopatologia , Varicocele/fisiopatologia , Adulto JovemRESUMO
OBJECTIVE: To evaluate varicocele effects on conventional semen parameters: sperm DNA fragmentation, chromatin packaging, mitochondrial membrane potential (MMP) and sperm apoptosis. METHODS: A cross-sectional study was carried out with semen samples from 2,399 men of couples who attended an infertility clinic. A total of 16.3% (391/2399) of the men were diagnosed with varicocele by a urologist. RESULTS: A regression analysis revealed that the percentages of sperm with DNA fragmentation, abnormal chromatin packaging, and abnormal MMP were significantly increased in individuals with varicocele, when compared to men without varicocele. Apoptosis was not influenced by varicocele. Conventional semen parameters were significantly worse in individuals with the disease. On the other hand, in men with varicocele, Spearman's correlation demonstrated that early apoptosis and abnormal MMP showed a positive and significant correlation with sperm DNA fragmentation. CONCLUSION: Men with varicocele had worse semen parameters, including increased levels of sperm DNA fragmentation, inactive mitochondria, and abnormal chromatin packaging. These changes are possible causes of infertility in individuals with varicocele.
Assuntos
Apoptose/fisiologia , Cromatina/metabolismo , Fragmentação do DNA , Potencial da Membrana Mitocondrial/fisiologia , Sêmen/metabolismo , Espermatozoides/metabolismo , Varicocele/fisiopatologia , Adulto , Estudos Transversais , Humanos , Masculino , Análise do Sêmen , Contagem de Espermatozoides , Motilidade dos Espermatozoides/fisiologia , Varicocele/metabolismoRESUMO
INTRODUCTION:: Varicocele disease is well-known cause of infertility in men. The presence of spermatic varices veins create a hostile environment to spermatogenesis. It results in reduced quality of the sperm production and in some cases can determine a total absence of sperm. The varicocelectomy procedure in patients with non-obstructive azoospermia (NOA) can raise the rates of sperm in the semen analysis. A positive rate for sperm, even if very low, may be sufficient to enable the capture of sperm intended for in-vitro fertilization without the use of donor sperm. OBJETIVE:: To evaluate the raise of sperm in NOA patients with varicocele disease who were submitted to a bilateral procedure to recovery sperm production. METHOD:: We analized the sperm results of 25 NOA patients who undergone to a bilateral varicocelectomy procedure. RESULTS:: From a total of 25 patients, three (12%) recovered sperm count four months after procedure. One year after the procedure, five (20%) patients recovered sperm production. CONCLUSION:: Patients with varicocele disease and azoospermia, without genetic changes or obstruction of the spermatic tract, should undergo surgical procedure to recover sperm.
Assuntos
Azoospermia/cirurgia , Espermatozoides , Varicocele/cirurgia , Azoospermia/fisiopatologia , Humanos , Masculino , Reprodutibilidade dos Testes , Estudos Retrospectivos , Contagem de Espermatozoides , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Varicocele/fisiopatologiaRESUMO
Varicocele is found in approximately 20% of adults and adolescents and in 19-41% of men seeking treatment for infertility. It is associated with a decrease in sperm count as well as sperm motility and morphology. The currently accepted description of the pathophysiology of varicocele does not explain all its clinical manifestations; therefore, other factors such as genetic and epigenetic changes, associated with the environment, might be involved in causing infertility and decrease in sperm quality. It has been reported that the varicocele-induced deterioration of testicular function is progressive and interferes with fertility; hence, early and efficient assessment of the genetic manifestations in patients would be important for developing future medical interventions. Chromosomal disorders, mutations, polymorphisms, changes in gene expression, and epigenetic changes have all been reported to be associated with varicocele. Several studies are underway to unravel the genetic basis of this disease, as it is important to understand the origin and the aggravating factors to ensure appropriate guidance and intervention. Here, we review the available literature regarding the genetic and epigenetic changes associated with varicocele, and how these alterations are related to the different clinical manifestations of the disease.
Assuntos
Epigênese Genética , Infertilidade Masculina/complicações , Varicocele/genética , Fragmentação do DNA , DNA Mitocondrial/química , Humanos , Infertilidade Masculina/genética , Masculino , Estresse Oxidativo , Análise do Sêmen , Varicocele/patologia , Varicocele/fisiopatologiaRESUMO
Summary Introduction: Varicocele disease is well-known cause of infertility in men. The presence of spermatic varices veins create a hostile environment to spermatogenesis. It results in reduced quality of the sperm production and in some cases can determine a total absence of sperm. The varicocelectomy procedure in patients with non-obstructive azoospermia (NOA) can raise the rates of sperm in the semen analysis. A positive rate for sperm, even if very low, may be sufficient to enable the capture of sperm intended for in-vitro fertilization without the use of donor sperm. Objetive: To evaluate the raise of sperm in NOA patients with varicocele disease who were submitted to a bilateral procedure to recovery sperm production. Method: We analized the sperm results of 25 NOA patients who undergone to a bilateral varicocelectomy procedure. Results: From a total of 25 patients, three (12%) recovered sperm count four months after procedure. One year after the procedure, five (20%) patients recovered sperm production. Conclusion: Patients with varicocele disease and azoospermia, without genetic changes or obstruction of the spermatic tract, should undergo surgical procedure to recover sperm.
Resumo Introdução: A varicocele é sabidamente uma das causas de infertilidade nos homens. A presença de veias espermáticas dilatadas pode criar um ambiente hostil para a espermatogênese. Isso é causa de baixa qualidade e quantidade da produção do esperma; em alguns casos, pode determinar uma ausência total de espermatozoides. O procedimento de varicocelectomia em pacientes com azoospermia não obstrutiva pode aumentar as taxas de espermatozoides na análise do sêmen. Uma taxa positiva para o esperma, mesmo se muito baixa, pode ser suficiente para permitir a coleta e destinar-se ao processo de fertilização in vitro. Isso sem a necessidade de usar esperma de doador. Objetivo: Avaliar o aumento de espermatozoides em pacientes com varicocele associada à azoospermia não obstrutiva. Método: Foram analisados os espermas de 25 pacientes azoospêrmicos não obstrutivos submetidos a procedimento de varicocelectomia bilateral com magnificação microcirúrgica. Resultados: De um total de 25 pacientes, em três (12%) ocorreu recuperação da contagem de espermatozoides quatro meses após o procedimento. Após um ano de procedimento, em cinco (20%) ocorreu a recuperação. Conclusão: Pacientes com ausência de espermatozoides e varicocele, sem alterações genéticas, devem ser submetidos a tratamento cirúrgico a fim de recuperar a produção de espermatozoides.
Assuntos
Humanos , Masculino , Espermatozoides , Varicocele/cirurgia , Azoospermia/cirurgia , Contagem de Espermatozoides , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Fatores de Tempo , Varicocele/fisiopatologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Resultado do Tratamento , Azoospermia/fisiopatologiaRESUMO
In recent years, the management of male factor infertility has undergone important changes with the introduction of novel concepts, advanced testing, and therapeutic interventions. This review highlights some of these changes and discusses their impact to routine clinical practice. First, we discuss the recent changes in the World Health Organization (WHO) laboratory methods and reference values for the examination of human semen. Second, we examine the role of sperm chromatin integrity tests in light of increasing evidence of the detrimental effect of sperm DNA fragmentation on reproductive outcomes. Third, we summarize the main findings of varicocele-related infertility and the outcomes of microsurgical varicocele repair to different case scenarios. Lastly, we critically discuss the current management of men with nonobstructive azoospermia seeking fertility and the new opportunities that emerged to help these men achieve biological fatherhood.
Assuntos
Azoospermia/fisiopatologia , Infertilidade Masculina/fisiopatologia , Espermatozoides/patologia , Varicocele/fisiopatologia , Azoospermia/diagnóstico , Cromatina/genética , Humanos , Infertilidade Masculina/diagnóstico , Masculino , Sêmen/fisiologia , Varicocele/diagnóstico , Organização Mundial da SaúdeRESUMO
OBJECTIVES: To study the impact of obesity, age and varicocele on sexual hormones of adult and elderly men. MATERIALS AND METHODS: 875 men who were screened for prostate cancer were enrolled in this study. Data recorded comprised age, body mass index (BMI), serum levels of total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH) and follicular stimulating hormone (FSH). Patients were divided in groups according to their BMI in underweight, normal weight, overweight and obese grades 1, 2 or 3. First, it was studied the association between age, BMI, and hormone profile. Then, clinical varicocele was evaluated in 298 patients to assess its correlation to the others parameters. RESULTS: Obese patients had lower levels of TT, FT and SHBG (p<0.001) compared to underweight or normal weight patients. There were no differences in age (p=0.113), FSH serum levels (p=0.863) and LH serum levels (p=0.218) between obese and non-obese patients. Obese grade 3 had lower levels of TT and FT compared to obese grade 1 and 2 (p<0.05). There was no difference in the SHBG levels (p=0.120) among obese patients. There was no association between varicocele and BMI; and varicocele did not impact on testosterone or SHBG levels. CONCLUSIONS: Men with higher BMI have a lower serum level of TT, FT and SHBG. The presence of clinical varicocele as well as its grade has no impact on hormone profile in elderly men.
Assuntos
Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Obesidade/sangue , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue , Varicocele/sangue , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Valores de Referência , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Varicocele/fisiopatologiaRESUMO
ABSTRACT Objectives: To study the impact of obesity, age and varicocele on sexual hormones fof adult and elderly men. Materials and Methods: 875 men who were screened for prostate cancer were enrolled in this study. Data recorded comprised age, body mass index (BMI), serum levels of total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH) and follicular stimulating hormone (FSH). Patients were divided in groups according to their BMI in underweight, normal weight, overweight and obese grades 1, 2 or 3. First, it was studied the association between age, BMI, and hormone profile. Then, clinical varicocele was evaluated in 298 patients to assess its correlation to the others parameters. Results: Obese patients had lower levels of TT, FT and SHBG (p<0.001) compared to underweight or normal weight patients. There were no differences in age (p=0.113), FSH serum levels (p=0.863) and LH serum levels (p=0.218) between obese and non-obese patients. Obese grade 3 had lower levels of TT and FT compared to obese grade 1 and 2 (p<0.05). There was no difference in the SHBG levels (p=0.120) among obese patients. There was no association between varicocele and BMI; and varicocele did not impact on testosterone or SHBG levels. Conclusions: Men with higher BMI have a lower serum level of TT, FT and SHBG. The presence of clinical varicocele as well as its grade has no impact on hormone profile in elderly men.
Assuntos
Humanos , Masculino , Idoso , Idoso de 80 Anos ou mais , Testosterona/sangue , Varicocele/sangue , Globulina de Ligação a Hormônio Sexual/análise , Hormônio Luteinizante/sangue , Hormônio Foliculoestimulante/sangue , Obesidade/sangue , Valores de Referência , Varicocele/fisiopatologia , Índice de Gravidade de Doença , Índice de Massa Corporal , Estudos Transversais , Fatores Etários , Estatísticas não Paramétricas , Pessoa de Meia-Idade , Obesidade/fisiopatologiaAssuntos
Infertilidade Masculina/etiologia , Varicocele/complicações , Humanos , Infertilidade Masculina/metabolismo , Infertilidade Masculina/fisiopatologia , Infertilidade Masculina/cirurgia , Infertilidade Masculina/terapia , Masculino , Técnicas de Reprodução Assistida , Varicocele/metabolismo , Varicocele/fisiopatologia , Varicocele/cirurgia , Varicocele/terapiaRESUMO
PURPOSE: This study aimed to investigate the protective effects of isolated and co-administration of vitamin E (VitE) and dexamethasone (DEX) on varicocele (VCL)-induced damages in testicular tissue. MATERIALS AND METHODS: Wistar rats were divided into five groups (n=6), including; control-sham, non-treated VCL-induced, VitE-treated VCL-induced (VitE, 150 mg/kg, orally), DEX-administrated VCL-induced (DEX, 0.125 mg/kg, i.p.), VitE+DEX-received VCL-induced animals. The antioxidant status analyses, histopathological examinations, hormonal assay and tissue levels of alkaline phosphatase (ALP) were analyzed. The germinal epithelium RNA damage and Leydig cells steroidogenesis were analyzed. Moreover, the Hsp70-2 protein expression was examined based on immunohistochemical and western blot analyses. The sperm parameters, DNA integrity and chromatin condensation were investigated. RESULTS: VitE and DEX in simultaneous form of administration significantly (P<0.05) down-regulated the tissue ALP level and attenuated the VCL-decreased GSH-px, SOD and TAC levels and remarkably (P<0.05) down-regulated the testicular malondialdehyde (MDA) and nitric oxide (NO) contents. The VCL-induced histopathological alterations significantly (P<0.05) improved in VitE and DEX-administrated animals. The VitE and DEX co-administration reduced the VCL-increased RNA damage and elevated the Leydig cells steroidogenic activity. The Hsp70-2 protein level completely (P<0.05) increased in VitE and DEX alone-and-simultaneous-administrated animals. Finally, the VitE and DEX could significantly (P<0.05) improve the VCL-decreased semen quality and improved the sperm DNA integrity and chromatin condensation. CONCLUSION: Our data suggest that Vit E by up-regulating the antioxidant status and DEX by reducing inflammation-dependent oxidative and nitrosative stresses could improve the VCL-reduced Hsp70-2 chaperone expression and ultimately protected the testicular endocrine activities and promoted the spermatogenesis process.
Assuntos
Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Dexametasona/administração & dosagem , Proteínas de Choque Térmico HSP70/metabolismo , Varicocele/tratamento farmacológico , Vitamina E/administração & dosagem , Animais , Western Blotting , Cromatina/fisiologia , Dano ao DNA , Modelos Animais de Doenças , Interações Medicamentosas , Glutationa Peroxidase/análise , Imuno-Histoquímica , Masculino , Malondialdeído/análise , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras , Ratos Wistar , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Superóxido Dismutase/análise , Testículo/efeitos dos fármacos , Testículo/enzimologia , Testículo/patologia , Testosterona/sangue , Varicocele/fisiopatologiaRESUMO
ABSTRACTPurpose:This study aimed to investigate the protective effects of isolated and co-administration of vitamin E (VitE) and dexamethasone (DEX) on varicocele (VCL)-induced damages in testicular tissue.Materials and Methods:Wistar rats were divided into five groups (n=6), including; control-sham, non-treated VCL-induced, VitE-treated VCL-induced (VitE, 150 mg/kg, orally), DEX-administrated VCL-induced (DEX, 0.125 mg/kg, i.p.), VitE+DEX-received VCL-induced animals. The antioxidant status analyses, histopathological examinations, hormonal assay and tissue levels of alkaline phosphatase (ALP) were analyzed. The germinal epithelium RNA damage and Leydig cells steroidogenesis were analyzed. Moreover, the Hsp70-2 protein expression was examined based on immunohistochemical and western blot analyses. The sperm parameters, DNA integrity and chromatin condensation were investigated.Results:VitE and DEX in simultaneous form of administration significantly (P<0.05) down-regulated the tissue ALP level and attenuated the VCL-decreased GSH-px, SOD and TAC levels and remarkably (P<0.05) down-regulated the testicular malondialdehyde (MDA) and nitric oxide (NO) contents. The VCL-induced histopathological alterations significantly (P<0.05) improved in VitE and DEX-administrated animals. The VitE and DEX co-administration reduced the VCL-increased RNA damage and elevated the Leydig cells steroidogenic activity. The Hsp70-2 protein level completely (P<0.05) increased in VitE and DEX alone–and-simultaneous-administrated animals. Finally, the VitE and DEX could significantly (P<0.05) improve the VCL-decreased semen quality and improved the sperm DNA integrity and chromatin condensation.Conclusion:Our data suggest that Vit E by up-regulating the antioxidant status and DEX by reducing inflammation-dependent oxidative and nitrosative stresses could improve the VCL-reduced Hsp70-2 chaperone expression and ultimately protected the testicular endocrine activities and promoted the spermatogenesis process.
Assuntos
Animais , Masculino , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Dexametasona/administração & dosagem , /metabolismo , Varicocele/tratamento farmacológico , Vitamina E/administração & dosagem , Western Blotting , Cromatina/fisiologia , Modelos Animais de Doenças , Dano ao DNA , Interações Medicamentosas , Glutationa Peroxidase/análise , Imuno-Histoquímica , Malondialdeído/análise , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras , Ratos Wistar , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Superóxido Dismutase/análise , Testículo/efeitos dos fármacos , Testículo/enzimologia , Testículo/patologia , Testosterona/sangue , Varicocele/fisiopatologiaRESUMO
Mammalian spermatogenesis is a complex biological process occurring in the seminiferous tubules in the testis. This process represents a delicate balance between cell proliferation, differentiation, and apoptosis. In most mammals, the testicles are kept in the scrotum 2 to 7°C below body core temperature, and the spermatogenic process proceeds with a blood and oxygen supply that is fairly independent of changes in other vascular beds in the body. Despite this apparently well-controlled local environment, pathologies such as varicocele or testicular torsion and environmental exposure to low oxygen (hypoxia) can result in changes in blood flow, nutrients, and oxygen supply along with an increased local temperature that may induce adverse effects on Leydig cell function and spermatogenesis. These conditions may lead to male subfertility or infertility. Our literature analyses and our own results suggest that conditions such as germ cell apoptosis and DNA damage are common features in hypoxia and varicocele and testicular torsion. Furthermore, oxidative damage seems to be present in these conditions during the initiation stages of germ cell damage and apoptosis. Other mechanisms like membrane-bound metalloproteinases and phospholipase A2 activation could also be part of the pathophysiological consequences of testicular hypoxia.
Assuntos
Testículo/metabolismo , Humanos , Hipóxia , Células Intersticiais do Testículo/metabolismo , Masculino , Espécies Reativas de Oxigênio/metabolismo , Torção do Cordão Espermático/fisiopatologia , Espermatogênese/fisiologia , Testículo/fisiopatologia , Varicocele/fisiopatologiaRESUMO
STUDY QUESTION: What are the effects of smoking on the functional aspects of the sperm, the levels of lipid peroxidation and the protein profile of seminal plasma in patients with varicocele? SUMMARY ANSWER: In men with varicocele, smoking is associated with altered semen quality, decreased sperm functional integrity and seminal oxidative stress. Alterations in seminal plasma protein profiles are also present and may explain the altered semen phenotype. WHAT IS KNOWN ALREADY: Varicocele is a major cause of male infertility. It reduces testicular blood renewal with a consequent accumulation of toxic substances. Thus, it can potentiate the toxic effects of environmental exposure to genotoxic substances such as those found in cigarette smoke. STUDY DESIGN, SIZE AND DURATION: A cross-sectional study was performed in 110 patients presenting with variococele to the Human Reproduction Section of the Sao Paulo Federal University (2006-2010). The patients were divided into a control group of non-smokers, a moderate smokers group and a heavy smokers group. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Semen parameters were analysed by standard methods. Sperm DNA integrity and mitochondrial activity were assessed by Comet assays and by 3,3'-diaminobenzidine deposition, respectively. The level of lipid peroxidation in semen was determined by malondialdehyde quantification. Proteomic studies were performed by 2D-electrophoresis and mass spectrometry. MAIN RESULTS AND THE ROLE OF CHANCE: Both groups of smokers showed reduced semen quality in comparison with the control group. In the groups of smokers, sperm DNA integrity and mitochondrial activity were also decreased and lipid peroxidation levels were increased. Proteomic analyses revealed 20 proteins differentially expressed between the study groups. LIMITATIONS AND REASONS FOR CAUTION: A study including smokers without varicocele is still warranted as these results apply only to smokers who present varicocele. WIDER IMPLICATIONS OF THE FINDINGS: Patients with varicocele who are exposed to tobacco smoking present more important alterations to semen quality and sperm functional integrity and show changes in the seminal plasma proteome. This suggests testicular, and possibly systemic, adverse effects of smoking. STUDY FUNDING/COMPETING INTEREST(S): Funding for the study was provided by Fundação de Amparo à Pesquisa do Estado de São Paulo (Fapesp) (2007/59423-7) and by the Division of Urology, Human Reproduction Section at the São Paulo Federal University.
Assuntos
Infertilidade Masculina/etiologia , Estresse Oxidativo , Proteínas de Plasma Seminal/metabolismo , Fumar/efeitos adversos , Espermatozoides/metabolismo , Varicocele/metabolismo , Adulto , Brasil , Estudos Transversais , Fragmentação do DNA , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Hospitais Universitários , Humanos , Peroxidação de Lipídeos , Masculino , Mitocôndrias/enzimologia , Mitocôndrias/metabolismo , Mapeamento de Peptídeos , Sêmen/química , Análise do Sêmen , Proteínas de Plasma Seminal/química , Índice de Gravidade de Doença , Espermatozoides/enzimologia , Espermatozoides/patologia , Varicocele/patologia , Varicocele/fisiopatologiaRESUMO
OBJECTIVE: To assess reproductive function in male ankylosing spondylitis (AS) patients in comparison to healthy controls. METHODS: Twenty AS patients were compared to 24 healthy male subjects with regard to demographic data, urological examination, testicular ultrasound (US), semen analysis, anti-sperm antibodies, and hormone profile. Exclusion criteria were present use of sulfasalazine or methotrexate, and ever use of biological/cytotoxic agents. Disease activity of AS was evaluated by clinical and laboratory assessments. RESULTS: Demographic data were similar in AS and controls (p = 0.175). Varicocele was found significantly more frequently in AS patients than in controls (40% vs. 8%, p = 0.027). Semen analysis revealed no significant differences in sperm quality between AS patients and controls (p > 0.05). By contrast, the median of normal sperm forms was significantly lower in AS patients with vs. those without varicocele [13.5 (range 2-27) vs. 22 (range 10-32.5)%, p = 0.049] whereas no difference in sperm morphology was observed comparing AS patients and controls without varicocele (p = 0.670). Comparison of AS patients with and without varicocele showed that anti-sperm antibodies, hormones, inflammatory markers, and disease activity scores did not contribute to the impaired sperm morphology observed in AS patients with varicocele. CONCLUSIONS: An increased frequency of varicocele was found in AS patients associated with sperm abnormalities but independent of therapy, anti-sperm antibodies, hormonal alterations, or disease parameters. Investigation for varicocele should be routine in AS patients with fertility problems.
Assuntos
Espondilite Anquilosante/fisiopatologia , Testículo/fisiopatologia , Varicocele/fisiopatologia , Adolescente , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Análise do Sêmen , Contagem de Espermatozoides , Motilidade dos Espermatozoides/fisiologia , Espondilite Anquilosante/complicações , Espondilite Anquilosante/diagnóstico por imagem , Testículo/diagnóstico por imagem , Ultrassonografia , Varicocele/complicações , Varicocele/diagnóstico por imagemRESUMO
OBJECTIVES: The most common indication for treatment of varicocele is still male subfertility. The aim of this study was to explore the effect of infertility duration on semen parameters and spontaneous pregnancy rate after varicocelectomy. MATERIALS AND METHODS: The medical records of 183 infertile patients with clinical varicocele were retrospectively reviewed. The patients were divided into three groups according to the duration of infertility (group I, 1-3 years, group II, 3-6 years and group III, > 6 years). Total sperm motility counts (TMCs) before and after varicocelectomy and spontaneous pregnancy rate among these groups were statistically compared. RESULTS: The greatest changes, regarding preoperative and postoperative TMCs and spontaneous pregnancy rate were noticed between group I and III. Preoperative TMCs in group I and III was 15.2 ± 1.2, 7.8 ± 1.4, respectively (p < 0.05). Postoperative TMCs in group I and III was 33.7 ± 2.5, 25.2 ± 1.9, respectively (p < 0.05). An overall spontaneous pregnancy rate of 34.4 percent was achieved after inguinal varicocelectomy. The greatest spontaneous pregnancy rate was achieved in Group I (37.3 percent), and the lowest pregnancy rate in Group III (26.3 percent) (P < 0.05). CONCLUSIONS: Surgical varicocelectomy improves the total sperm motility counts especially in patients who have a TMCS more than 5 million and improves the spontaneous pregnancy rates. The improvement in the spontaneous pregnancy rates after varicocelectomy correlates negatively with the duration of infertility. Therefore, duration of infertility should be considered in treating a patient with a varicocele as a cause of infertility.