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Urogenital inflammation is a known cause of male infertility. Increased levels of inflammatory cytokines, leukocyte counts and oxidative stress are highly detrimental for sperm quality thus compromising male fertility. Although cytokines affect sperm by recruiting and activating leukocytes consequently inducing tissue inflammation and oxidative stress, scarce to absent data have been reported about the putative direct effects of inflammatory cytokines on spermatozoa. Herein, we analyzed whether IFNγ, IL-17A, IL-1ß, and IL-8 can alter human sperm motility and viability per se. Fractions of viable and motile spermatozoa from normospermic healthy donors were in vitro incubated with recombinant human IFNγ, IL-17A, IL-1ß or IL-8 and sperm ROS production, motility, viability and apoptosis were analyzed. Sperm exposed to different concentrations of IFNγ, IL-17A and IL-1ß, or a combination of them, for either 1 or 3 h showed significantly increased levels of mitochondrial ROS production and reduced motility and viability with respect to sperm incubated with vehicle. Moreover, the exposure to IFNγ, IL-17A and IL-1ß resulted in significantly higher levels of early and/or late apoptotic and/or necrotic spermatozoa. Interestingly, no significant differences in sperm motility, viability and apoptosis were observed in sperm incubated with the concentrations of IL-8 analyzed, for either 1 or 3 h, with respect to sperm incubated with vehicle. In conclusion, our results indicate that IFNγ, IL-17A and IL-1ß per se impair sperm motility and decreases viability by triggering increased mitochondrial ROS production and inducing sperm apoptosis. Our results suggest that screening inflammatory cytokines in semen would be an additional helpful tool for the diagnostic workup of male infertility.
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Infertilidade Masculina , Motilidade dos Espermatozoides , Apoptose , Citocinas , Humanos , Inflamação , Interferon gama/farmacologia , Interleucina-17 , Interleucina-1beta , Interleucina-8 , Masculino , Espécies Reativas de Oxigênio , EspermatozoidesRESUMO
Chlamydia trachomatis is the most commonly reported agent of sexually transmitted bacterial infections worldwide. This pathogen frequently leads to persistent, long-term, subclinical infections, which in turn may cause severe pathology in susceptible hosts. This is in part due to the strategies that Chlamydia trachomatis uses to survive within epithelial cells and to evade the host immune response, such as subverting intracellular trafficking, interfering signaling pathways and preventing apoptosis. Innate immune receptors such as toll-like receptors expressed on epithelial and immune cells in the genital tract mediate the recognition of chlamydial molecular patterns. After bacterial recognition, a subset of pro-inflammatory cytokines and chemokines are continuously released by epithelial cells. The innate immune response is followed by the initiation of the adaptive response against Chlamydia trachomatis, which in turn may result in T helper 1-mediated protection or in T helper 2-mediated immunopathology. Understanding the molecular mechanisms developed by Chlamydia trachomatis to avoid killing and host immune response would be crucial for designing new therapeutic approaches and developing protective vaccines. In this review, we focus on chlamydial survival strategies and the elicited immune responses in male genital tract infections.
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Antígenos de Bactérias/imunologia , Infecções por Chlamydia/imunologia , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/imunologia , Genitália Masculina/imunologia , Imunidade Inata , Animais , Interações Hospedeiro-Patógeno , Humanos , Masculino , Viabilidade MicrobianaRESUMO
Chlamydia trachomatis is an obligate intracellular pathogen and the leading bacterial cause of sexually transmitted infections worldwide. Chlamydia trachomatis genovars L1-L3 are responsible for lymphogranuloma venereum (LGV), an invasive sexually transmitted disease endemic in tropical and subtropical regions of Africa, South America, the Caribbean, India and South East Asia. The typical signs and symptoms of C. trachomatis LGV urogenital infections in men include herpetiform ulcers, inguinal buboes, and/or lymphadenopathies. Since 2003, endemic cases of proctitis and proctocolitis caused by C. trachomatis LGV emerged in Europe, mainly in HIV-positive men who have sex with men (MSM). Scarce data have been reported about unusual clinical presentations of C. trachomatis LGV urogenital infections. Herein, we report a case of a 36-year-old heterosexual, HIV-negative male declaring he did not have sex with men or trans women, who presented to the Urology and Andrology outpatient clinic of a healthcare center from Cordoba, Argentina, with intermittent testicular pain over the preceding 6 months. Doppler ultrasound indicated right epididymitis and funiculitis. Out of 17 sexually transmitted infections (STIs) investigated, a positive result was obtained only for C. trachomatis. Also, semen analysis revealed oligoasthenozoospermia, reduced sperm viability as well as increased sperm DNA fragmentation and necrosis, together with augmented reactive oxygen species (ROS) levels and the presence of anti-sperm IgG autoantibodies. In this context, doxycycline 100 mg/12 h for 45 days was prescribed. A post-treatment control documented microbiological cure along with resolution of clinical signs and symptoms and improved semen quality. Strikingly, sequencing of the ompA gene revealed C. trachomatis LGV L2 as the causative uropathogen. Remarkably, the patient did not present the typical signs and symptoms of LGV. Instead, the infection associated with chronic testicular pain, semen inflammation and markedly reduced sperm quality. To our knowledge, this is the first reported evidence of chronic epididymitis due to C. trachomatis LGV L2 infection in an HIV-negative heterosexual man. These findings constitute important and valuable information for researchers and practitioners and highlight that C. trachomatis LGV-L2 should be considered as putative etiologic agent of chronic epididymitis, even in the absence of the typical LGV signs and symptoms.
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Epididimite , Infecções por HIV , Linfogranuloma Venéreo , Minorias Sexuais e de Gênero , Humanos , Masculino , Feminino , Adulto , Chlamydia trachomatis/genética , Linfogranuloma Venéreo/diagnóstico , Linfogranuloma Venéreo/epidemiologia , Linfogranuloma Venéreo/microbiologia , Homossexualidade Masculina , Heterossexualidade , Epididimite/complicações , Análise do Sêmen , Doença Crônica , Infecções por HIV/complicaçõesRESUMO
Introduction: COVID-19 exerts deleterious effects on the respiratory, cardiovascular, gastrointestinal, and central nervous systems, causing more severe disease in men than in women. However, cumulative reported data about the putative consequences on the male reproductive tract and fertility are controversial. Furthermore, the long-term effects of SARS-CoV-2 infection are still uncertain. Methods: In this study, we prospectively evaluated levels of inflammatory cytokines and leukocytes in semen and sperm quality parameters in a cohort of 231 reproductive-aged male patients, unvaccinated, who had recovered from mild or severe COVID-19 and in 62 healthy control individuals. Sperm quality was assessed early (less than 3 months) and long (more than 3 and up to 6 months) after having COVID-19. Interestingly, and unlike most reported studies, available extensive background and baseline data on patients' sperm quality allowed performing a more accurate analysis of COVID-19 effects on sperm quality. Results: Significantly higher levels of IL-1ß, TNF and IFNγ were detected in semen from patients recently recovered from mild and/or severe COVID-19 with respect to control individuals indicating semen inflammation. Moreover, patients recovered from mild and/or severe COVID-19 showed significantly reduced semen volume, lower total sperm counts, and impaired sperm motility and viability. Interestingly, all observed alterations returned to baseline values after 3 or more months after disease recovery. Discussion: These results indicate that COVID-19 associates with semen inflammation and impaired semen quality early after disease. However, long COVID-19 seems not to include long-term detrimental consequences on male fertility potential since the observed alterations were reversible after 1-2 spermatogenesis cycles. These data constitute compelling evidence allowing a better understanding of COVID-19 associated sequelae, fundamental for semen collection in assisted reproduction.
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COVID-19 is known to have deleterious effects on different systems such as the respiratory, cardiovascular, central nervous, and gastrointestinal. However, conflicting data about the possible implications for male reproductive health and fertility have been reported. In addition, the long-term consequences of SARS-CoV-2 infection remain unclear. Herein, we report a case of a 42-year-old man with no known co-morbidities and normal baseline semen quality, who subsequently suffered an asymptomatic SARS-CoV-2 infection. Shortly after, the patient developed sudden oligoasthenozoospermia, even reaching azoospermia, which gradually evolved into persistent severe oligonecrozoospermia, accompanied by semen inflammation and oxidative stress. Remarkably, the latter occurred in the absence of urogenital infections, hormonal imbalances, tissue/organ obstruction/damage, medication or drug treatment, smoking, or exposure to toxins/pollutants, radiation, or high temperature. This case constitutes valuable clinical evidence that adds to the current knowledge in the field and highlights the need for further and longer follow-up studies to better understand the putative long-term consequences of SARS-CoV-2 infection on male fertility.
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Introduction: In a previous study we found that ghrelin (Ghrl) misbalance during the peri-implantation period significantly impaired fetus development. In this study we aimed to evaluate the putative mechanisms underlying these effects, including embryo implantation success, uterine nitric oxide synthase (NOS) activity, nitric oxide synthesis and the inflammatory/immune uterine profile. Methods: Ghrelin misbalance was induced by injecting 4nmol/animal/day of Ghrl (hyperghrelinemia) or 6nmol/animal/day of a Ghrl antagonist (Ant: (D-Lys3)GHRP-6) from day 3 to 8 of pregnancy. Control animals (C) were injected with de vehicle. Females were euthanized at pregnancy day 8 and their uteri excised in order to evaluate: the percentage of reabsorbed embryos (microscopically), eNOS, iNOS and nytrotirosine expression (by immunohistochemistry), nitrite synthesis (by Griess technique), VEGF, IL-10, IL-17, IL-6, MMP9 and GM-CSF expression (by qPCR) and leukocyte infiltration by flow cytometry (evaluating T cells, NK cells, granulocytes, dendritic cells and macrophages). Results: Ant-treatment significantly increased the percentage of reabsorbed embryos and the uterine expression of eNOS, iNOS and nytrotirosine. (D-Lys3)GHRP-6-treatment increased also the expression of the inflammatory cytokines IL-6, IL-17 and MMP9, and decreased that of IL-10 (anti-inflammatory). Moreover, Ant-treatment increased also the NK cells population and that of CD11b+ dendritic cells; and decreased T cells percentages. Similarly, hyperghrelinemia showed a significant increase vs. C on eNOS, iNOS and nytrotirosineuterine expression and a decrease in T cells percentages. Conclusion: Ghrl misbalance during the peri-implantation period induces pro-inflammatory changes and nitrosative stress in the gravid uterus, impairing significantly embryo implantation and/or development.
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Interleucina-10 , Interleucina-17 , Feminino , Gravidez , Camundongos , Animais , Metaloproteinase 9 da Matriz , Grelina/farmacologia , Estresse Nitrosativo , Interleucina-6 , Implantação do Embrião , ÚteroRESUMO
PURPOSE: Chlamydia trachomatis infection of the male genital tract was proposed to alter male fertility. We studied the putative consequences of chlamydial male genital tract infection on semen quality and male fertility in an experimental rat model of infection. MATERIALS AND METHODS: We used 36 male and 40 female Wistar rats. Male genital infection was created by inoculating Chlamydia muridarum in the meatal urethra. The presence of C. muridarum was evaluated by polymerase chain reaction in semen and male genital tract organs early (15 days) and late (80 days) after infection. Sperm quality parameters were assayed in seminal and epididymal sperm from sham infected and infected rats. Mating studies with sexually mature females were performed and fertility parameters were assayed, including potency, fecundity and fertility indexes, fetal size, and pre-implantation and post-implantation embryo loss. RESULTS: Male rats showed ascending, disseminated infection 15 days after infection. Bacteria persisted in the prostate and seminal vesicles 80 days after infection. C. muridarum was detected in semen in most rats regardless of acute or chronic infection. Seminal or epididymal sperm quality did not differ in infected and sham infected rats 15 or 80 days after infection. Sperm apoptosis was also minimal in infected rats. No differences were observed in fertility parameters between infected and sham infected rats. CONCLUSIONS: C. muridarum infects the rat male genital tract and persists mainly in the prostate. Although C. muridarum was detected in semen during acute and chronic infection, no alterations in sperm quality were observed. C. muridarum infection does not impair male fertility.
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Infecções por Chlamydia/complicações , Chlamydia muridarum , Infertilidade Masculina/etiologia , Infecções do Sistema Genital/complicações , Animais , Modelos Animais de Doenças , Feminino , Masculino , Próstata/microbiologia , Prostatite/complicações , Prostatite/microbiologia , Ratos , Ratos Wistar , Infecções do Sistema Genital/microbiologia , SêmenRESUMO
PURPOSE: We investigated Chlamydia trachomatis infection and its pathogenic consequences in the male rodent genital tract. MATERIALS AND METHODS: Male rats were inoculated in the meatal urethra with Chlamydia muridarum. We sought bacterial DNA at early and late times after inoculation in different parts of the male genital tract. Histological alterations and the immune response against prostate antigens were analyzed. RESULTS: Male rats showed ascending infection with wide dissemination of bacteria in the genital tract at an early time point after inoculation. At later stages bacteria persisted only in some parts of the genital tract and in the prostate gland. C. muridarum was also detected in semen in a high proportion of rats irrespective of an acute or chronic stage of infection. Histological alterations that accompanied C. muridarum were especially observed in the prostate and mainly composed of CD3+ cell infiltration. Positive humoral and cellular responses against prostate antigens were noted in a considerable number of infected rats. NOD mice, an autoimmune, prostatitis prone strain, showed a similar pattern with C. muridarum in the prostate of 100% of infected mice, which was again accompanied by mononuclear cell infiltration and antibodies against prostate antigens at early and late times after inoculation. CONCLUSIONS: Results reveal that C. muridarum infects the male rodent genitourinary tract with special persistence in the prostate gland, where it causes chronic inflammation that in turn may act as a trigger factor for self-immune reactions in susceptible hosts.
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Autoimunidade , Infecções por Chlamydia/imunologia , Chlamydia muridarum , Doenças Urogenitais Masculinas/imunologia , Doenças Urogenitais Masculinas/microbiologia , Próstata/microbiologia , Animais , Autoimunidade/genética , Infecções por Chlamydia/genética , Modelos Animais de Doenças , Predisposição Genética para Doença , Masculino , Doenças Urogenitais Masculinas/genética , Camundongos , Camundongos Endogâmicos NOD , Ratos , Ratos WistarRESUMO
Female and male infertility have been associated to Chlamydia trachomatis, Ureaplasma spp. and Mycoplasma hominis urogenital infections. However, evidence from large studies assessing their prevalence and putative associations in patients with infertility is still scarce. The study design was a cross-sectional study including 5464 patients with a recent diagnosis of couple's primary infertility and 404 healthy control individuals from Cordoba, Argentina. Overall, the prevalence of C. trachomatis, Ureaplasma spp. and M. hominis urogenital infection was significantly higher in patients than in control individuals (5.3%, 22.8% and 7.4% vs. 2.0%, 17.8% and 1.7%, respectively). C. trachomatis and M. hominis infections were significantly more prevalent in male patients whereas Ureaplasma spp. and M. hominis infections were more prevalent in female patients. Of clinical importance, C. trachomatis and Ureaplasma spp. infections were significantly higher in patients younger than 25 years. Moreover, Ureaplasma spp. and M. hominis infections were associated to each other in either female or male patients being reciprocal risk factors of their co-infection. Our data revealed that C. trachomatis, Ureaplasma spp. and M. hominis are prevalent uropathogens in patients with couple's primary infertility. These results highlight the importance of including the screening of urogenital infections in the diagnostic workup of infertility.
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Infecções por Chlamydia/diagnóstico , Infertilidade Feminina/microbiologia , Infertilidade Masculina/microbiologia , Infecções por Mycoplasma/diagnóstico , Infecções por Ureaplasma/diagnóstico , Adulto , Infecções por Chlamydia/complicações , Chlamydia trachomatis/isolamento & purificação , Estudos Transversais , Feminino , Humanos , Infertilidade Feminina/etiologia , Infertilidade Masculina/etiologia , Masculino , Pessoa de Meia-Idade , Infecções por Mycoplasma/complicações , Mycoplasma hominis/isolamento & purificação , Ureaplasma/isolamento & purificação , Infecções por Ureaplasma/complicaçõesRESUMO
PURPOSE: An autoimmune etiology is proposed in some patients with chronic nonbacterial prostatitis since they show interferon-gamma secreting lymphocytes specific to prostate antigens in the periphery and increased interferon-gamma in seminal plasma. We investigated the involvement of interferon-gamma in an animal model of autoimmune prostatitis. MATERIALS AND METHODS: Experimental autoimmune prostatitis was studied in the no-obese diabetic and C57Bl/6 (Harlan, Zeist, The Netherlands) susceptible mouse strains, and in the IRF-1 KO and STAT-1 KO mouse strains deficient in transcription factors involved in interferon-gamma signaling. RESULTS: Experimental autoimmune prostatitis was characterized by prostate specific interferon-gamma secreting cells in the periphery and by T-helper 1 related cytokines in the target organ. Increased interferon-gamma and interleukin-12 were observed in the prostate of autoimmune animals while interleukin-10 and interleukin-4 were decreased and unaltered, respectively. The absence of transcription factors involved in the interferon-gamma signaling cascade, IRF-1 and STAT-1, made mice resistant to experimental autoimmune prostatitis. IRF-1 KO and STAT-1 KO mice immunized with prostate antigens did not show infiltration or alterations in the prostate. They did not have the typical prostate specific autoimmune response and showed decreased interferon-gamma, interleukin-12 and interleukin-10, and augmented interleukin-4 in the prostate. CONCLUSIONS: Our results argue for a crucial role of interferon-gamma as a key factor in the pathogenesis of the disease. Intense research is promptly required to identify the pathogenic mechanisms underlying chronic prostatitis/chronic pelvic pain syndrome to find a more rational therapy.
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Doenças Autoimunes/imunologia , Interferon gama/fisiologia , Prostatite/imunologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NODRESUMO
Chronic non bacterial prostatitis is a chronic inflammatory syndrome. Its etiology and physiopathology are unclear and treatments are empirical and ineffective in most cases. Autoimmunity has been proposed as an etiology. In the present report, we investigated the impact of vitamin D receptor silencing, by use of VDR-KO NOD mice and the immune-modulating effect of the vitamin D3 analog TX527 on the development of Experimental Autoimmune Prostatitis in NOD mice. VDR-KO NOD mice developed a more aggressive form of autoimmune prostatitis characterized by a greater lymphoproliferative response against prostate antigen in vitro (6.92+/-4.77 vs. 2.47+/-0.41 21 days after disease induction, p<0.05) and higher levels of specific INFgamma secretion (471+/-6 vs. 386+/-5pg/ml, p<0.01). This was accompanied in vivo by more severe lesions and augmented mononuclear cell infiltration in the prostate gland. On the other hand, although analog-treated mice showed a significant reduction in the spleen T-cell specific proliferative response against prostate antigen in vitro, no effect on disease development was observed. We conclude that vitamin D receptor modulation holds the promise of interfering with autoimmune prostatitis. Introduction of more powerful analogs, or combinations with anti-T-cell reagents may represent therapeutic solutions for these group of patients.
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Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Prostatite/imunologia , Prostatite/metabolismo , Receptores de Calcitriol/imunologia , Receptores de Calcitriol/metabolismo , Alcinos/uso terapêutico , Animais , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/genética , Doenças Autoimunes/patologia , Células Cultivadas , Colecalciferol/uso terapêutico , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos Knockout , Prostatite/tratamento farmacológico , Prostatite/genética , Prostatite/patologia , Receptores de Calcitriol/deficiência , Receptores de Calcitriol/genéticaRESUMO
The prostate is the target of many inflammatory and neoplastic disorders that affect men of all ages. Pathological conditions of the prostate gland range from infection of this organ by ascending bacteria from infected urine, to chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) of a still unknown etiology (accompanied with inflammation and lymphocyte infiltration of the gland), to benign hyperplasia and cancer. Patients under 50 years of age usually suffer from CP/CPPS, a chronic inflammatory syndrome characterized by pelvic pain, irritative voiding symptoms, and sexual dysfunction complaints. In this review, we summarize the current knowledge regarding immunological alterations present in CP/ CPPS patients. Remarkably, an inflammation state, in the absence of an invading infectious agent, is established in these patients, suggesting that an autoimmune process could be involved. In fact, specific autoimmune response to prostate antigens has recently been reported in CP/CPPS patients. Autoimmune response to prostate gland affects the seminal quality reported in these patients and may have critical consequences in their fertility. It is anticipated that preclinical studies in experimental models for CP/CPSS will provide important insights into the etiopathogenic mechanisms involved in this disease. We discuss here the similarities and the differences between human disease and experimental models and argue for the importance of the prostate gland in male reproductive function. Ultimately, we suggest that a state of inflammation, originally incited by an autoimmune response within the prostate, together with a diminished prostate functionality, may compromise male fertility.
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Doenças Autoimunes/etiologia , Prostatite/etiologia , Prostatite/imunologia , Animais , Doença Crônica , Modelos Animais de Doenças , Humanos , Tolerância Imunológica , Masculino , Dor Pélvica/etiologia , Dor Pélvica/imunologiaRESUMO
Despite the prevalence of prostate disease, little is known about the immunobiology of the prostate and its contribution to disease. The main goal of this work was to investigate how prostate epithelial cells deal with inflammatory stimuli. To this aim, we stimulated a rat prostate epithelial cell line [metastasis-lung (MAT-LU)] or rat primary epithelial cells with lipopolysaccharide (LPS). Prostate epithelial cells constitutively express significant levels of Toll-like receptor 4 (TLR4) and CD14 mRNA. TLR2 transcription could also be demonstrated, suggesting that these cells could recognize a broader spectrum of microbial molecular patterns. TLR4, TLR2, and CD14 proteins were also detected, although not at the cell surface but intracellularly. Prostate epithelial cells not only express these receptors, but they are also able to respond to LPS, and LPS-stimulated MAT-LU cells activate nuclear factor-kappaB transcription factor, induce the expression of inducible nitric oxide (NO) synthase, and secrete NO. Even more, numerous chemokine genes are up-regulated or induced in this response. Our results clearly demonstrate that prostate epithelial cells are fully competent to respond. The fact that they express TLR4 and TLR2 intracellularly suggests the presence of regulatory mechanisms, which once overcome, could turn these cells into active players of the innate immunity, capable of initiating an inflammatory response.
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Células Epiteliais/imunologia , Infecções/imunologia , Mediadores da Inflamação/metabolismo , Próstata/imunologia , Prostatite/imunologia , Receptor 4 Toll-Like/metabolismo , Animais , Linhagem Celular Tumoral , Células Cultivadas , Células Epiteliais/metabolismo , Imunidade Inata/genética , Imunidade Inata/imunologia , Infecções/fisiopatologia , Receptores de Lipopolissacarídeos/genética , Receptores de Lipopolissacarídeos/metabolismo , Lipopolissacarídeos , Masculino , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Próstata/citologia , Próstata/fisiopatologia , Prostatite/induzido quimicamente , Prostatite/fisiopatologia , RNA Mensageiro/imunologia , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Regulação para Cima/genética , Regulação para Cima/imunologiaRESUMO
Chlamydia trachomatis (CT) is the most prevalent cause of sexually transmitted diseases. Although the prevalence of chlamydial infection is similar in men and women, current research and screening are still focused on women, who develop the most severe complications, leaving the study of male genital tract (MGT) infection underrated. Herein, we reviewed the literature on genital CT infection with special focus on the MGT. Data indicate that CT certainly infects different parts of the MGT such as the urethra, seminal vesicles, prostate, epididymis and testis. However, whether or not CT infection has detrimental effects on male fertility is still controversial. The most important features of CT infection are its chronic nature and the presence of a mild inflammation that remains subclinical in most individuals. Chlamydia antigens and pathogen recognition receptors (PRR), expressed on epithelial cells and immune cells from the MGT, have been studied in the last years. Toll-like receptor (TLR) expression has been observed in the testis, epididymis, prostate and vas deferens. It has been demonstrated that recognition of chlamydial antigens is associated with TLR2, TLR4, and possibly, other PRRs. CT recognition by PRRs induces a local production of cytokines/chemokines, which, in turn, provoke chronic inflammation that might evolve in the onset of an autoimmune process in genetically susceptible individuals. Understanding local immune response along the MGT, as well as the crosstalk between resident leukocytes, epithelial, and stromal cells, would be crucial in inducing a protective immunity, thus adding to the design of new therapeutic approaches to a Chlamydia vaccine.
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Infecções por Chlamydia/imunologia , Chlamydia trachomatis/imunologia , Genitália Masculina/metabolismo , Imunoterapia , Infertilidade/imunologia , Infecções Sexualmente Transmissíveis/imunologia , Antígenos de Bactérias/imunologia , Autoimunidade , Infecções por Chlamydia/terapia , Feminino , Genitália Masculina/imunologia , Genitália Masculina/microbiologia , Humanos , Imunidade Inata , Infertilidade/terapia , Mediadores da Inflamação/metabolismo , Masculino , Receptores de Reconhecimento de Padrão/metabolismo , Infecções Sexualmente Transmissíveis/terapiaRESUMO
OBJECTIVES: The role of Chlamydia trachomatis (CT) in the pathogenesis of chronic prostatitis and its impact on male fertility remain controversial. The aim of this study was to assess the occurrence of chlamydial infection in chronic prostatitis patients and its impact on semen quality. METHODS: Urine and semen samples were assayed for the presence of microbial infection. CT-specific IgG and IgA antibodies were measured in serum and seminal plasma. Semen parameter analysis, anti-sperm antibody determinations and inflammatory cytokines measurements were performed. RESULTS: CT was detected in 10% of semen from chronic prostatitis patients. CT-specific IgG and IgA were found in 7.5% and 32.5% of the seminal plasma and in 15.0% and 2.5% of the serum samples from patients. Most of the patients that evidenced CT infection also evidenced CT-specific antibodies either in semen or in serum. We found that chlamydial infection has no detrimental effects on sperm quality. We neither found abnormal levels of serum PSA nor of seminal inflammatory cytokines in CT-infected patients. CONCLUSIONS: Our results support the potential role of CT in chronic prostatitis, its importance in diagnosis and that this infection does not seriously compromise sperm quality.
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Infecções por Chlamydia/complicações , Infecções por Chlamydia/fisiopatologia , Chlamydia trachomatis/isolamento & purificação , Prostatite/complicações , Espermatozoides/microbiologia , Espermatozoides/fisiologia , Adulto , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/isolamento & purificação , Infecções por Chlamydia/microbiologia , Doença Crônica , Humanos , Imunoglobulina A/sangue , Imunoglobulina A/isolamento & purificação , Imunoglobulina G/sangue , Imunoglobulina G/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Sêmen/imunologiaRESUMO
OBJECTIVE: To report the finding of red and brownish precipitates with morphology and chemistry compatible with uric acid crystals in semen in a patient with symptoms of chronic prostatitis. DESIGN: Case report. SETTING: Academic clinical biochemistry and immunology laboratory. PATIENT(S): A 35-year-old man with clinical symptoms of prostatitis. INTERVENTION(S): Uric acid crystals were detected in the semen samples. Treatment with a low purine diet relieved the symptoms. MAIN OUTCOME MEASURE(S): Study of chemical and morphological characteristics of crystals found in the semen using standard semen analysis and transrectal ultrasound. Analysis of serum, urine, and seminal plasma uric acid levels. RESULT(S): Uric acid crystals were detected in semen. A transrectal ultrasound revealed the presence of microcalcifications in the prostate gland. After treatment with a low purine diet, the patient experienced considerable relief of the clinical symptoms. Determination of uric acid and creatinine levels in serum and seminal plasma were carried out before and after treatment. There were no abnormalities or presence of crystals in the post-treatment semen analysis. CONCLUSION(S): The presence of uric acid crystals in semen of a patient with symptoms of chronic prostatitis can be attributed to the pelvic pain.
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Dor Pélvica/etiologia , Prostatite/complicações , Prostatite/metabolismo , Sêmen/metabolismo , Ácido Úrico/metabolismo , Adulto , Doença Crônica , Cristalização , Dieta , Humanos , Masculino , Prostatite/diagnóstico por imagem , Prostatite/dietoterapia , Purinas/administração & dosagem , UltrassonografiaRESUMO
Acute and chronic infectious prostatitis are the best understood of the prostate syndromes, but they are the least frequent. In contrast, although chronic non-infectious prostatitis is the most frequent syndrome, its cause has proved elusive despite years of investigation. In the present study, we analyzed a group of patients with infectious and non-infectious chronic prostatitis in order to search for the presence of a possible autoimmune response to prostate antigens. We demonstrated the presence of lymphocytes able to proliferate in response to known human prostate antigens such as PSA and PAP only in a group of patients with non-infectious chronic prostatitis. We observed that, as in other autoimmune diseases, a proliferative response against two or more autoantigens was a common feature. Moreover, when INFgamma and IL-10 levels were measured in culture supernatants, significantly elevated levels of INFgamma were detected only in samples from patients with positive proliferative response to prostate antigens. Interestingly, only these patients showed significantly elevated levels of inflammatory cytokines (IL-1 and TNF-alpha) in seminal plasma, arguing for a local inflammation of non-infectious cause. Our results show that INFgamma-secreting lymphocytes specific to prostate antigens are in fact detected in 34% of the patients with chronic non-infectious prostatitis. We speculate that these cells could be involved in the inflammatory process taking place in the prostate gland and therefore could alter its biological function.
Assuntos
Antígenos/imunologia , Interferon gama/metabolismo , Linfócitos/imunologia , Próstata/imunologia , Prostatite/imunologia , Fosfatase Ácida , Adulto , Formação de Anticorpos/imunologia , Apresentação de Antígeno/imunologia , Autoimunidade/imunologia , Proliferação de Células , Doença Crônica , Líquido Extracelular/imunologia , Líquido Extracelular/metabolismo , Humanos , Imunidade Celular/imunologia , Interleucina-1/metabolismo , Interleucina-10/metabolismo , Leucócitos Mononucleares/imunologia , Ativação Linfocitária/imunologia , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/imunologia , Proteínas Tirosina Fosfatases/imunologia , Sêmen/química , Sêmen/imunologia , Sêmen/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: The relationship between chronic prostatitis and fertility has been controversial for many years. We have previously shown the presence of a cellular autoimmune response against prostate antigens in a group of chronic prostatitis patients. Our main goal was to investigate whether chronic prostatitis (either caused by an infection or an autoimmune response to the prostate gland) could have a deleterious effect on semen quality. METHODS: Forty-four patients diagnosed as suffering from chronic prostatitis were included and divided into groups according to the presence of infection and/or cellular autoimmune response against prostate antigens. Healthy normal individuals were included as controls. Measurements for sperm concentration, motility, morphology, prostate and seminal vesicle markers, antisperm antibodies, white blood cells and pro-inflammatory cytokines were performed accordingly. RESULTS: The most severe abnormalities were seen in patients with no evident infection and an autoimmune response against prostate antigens. Moreover, significantly increased levels of pro-inflammatory cytokines were detected in seminal plasma from these patients. CONCLUSIONS: This study shows that chronic prostatitis patients with cellular autoimmune response to prostate antigens present important alterations in their semen quality parameters. We speculate that an autoimmune response against prostate antigens and the inflammatory process involved may affect male fertility.
Assuntos
Doenças Autoimunes/imunologia , Infertilidade Masculina/imunologia , Próstata/imunologia , Prostatite/imunologia , Sêmen/imunologia , Adulto , Autoantígenos/imunologia , Doenças Autoimunes/complicações , Doenças Autoimunes/patologia , Doença Crônica , Humanos , Infecções/imunologia , Infecções/patologia , Infertilidade Masculina/etiologia , Infertilidade Masculina/patologia , Masculino , Pessoa de Meia-Idade , Prostatite/complicações , Prostatite/patologiaRESUMO
Although there is no reliable single laboratory test available for the diagnosis of cow's milk allergy, if an allergic mechanism is suspected, a number of laboratory studies may be useful in delineating specific proteins responsible for these disorders. In the current study we analyzed in vitro lymphocyte proliferation assays, specific secretion of TNFalpha in supernatant cultures and specific IgE, IgG, and IgA in a group of patients with hypersensitivity to cow's milk antigens. The stimulation index against a cow's milk antigen mixture, alpha-lactalbumin, beta-lactoglobulin, and casein was significant higher in the group of patients maintained on cow's milk-free diet for less than 4 months compared with the values observed in the control group and in the group of patients without a close contact to cow's milk proteins. A significant increase in TNF-alpha secretion was observed in supernatants from patients with close contact to cow's milk (CM). Specific IgE was detected in 59.3% of the patients, with higher specific IgE levels in patients who were not positive for the proliferation assay, suggesting a clear difference in the two mechanisms proposed as effectors in this disease. No differences in specific IgG and IgA levels were observed between the patient group and the control group, with a great dispersion among individuals in all groups tested. We conclude that a combination of the assays tested in this study, such as proliferative assay of peripheral blood mononuclear cells to CM, the quantitation of TNFalpha in culture supernatants, and serum specific IgE determination, are useful laboratory tests to identify cow's milk allergy among patients with immediate and non immediate adverse reactions, reducing the need for food allergen challenges in young children.