RESUMO
The aim of this work was to study effects of ketotifen fumarate (KF) on prevention of tissue damage in testes of rats with experimental autoimmune orchitis (EAO) and on the contralateral testis in a model of prolonged testicular cord torsion (TCT). Rats with EAO or TCT were injected intraperitoneally once daily with KF or saline solution (vehicle group). Incidence and severity of testicular damage were evaluated by histopathology using an EAO score or a Johnsen score. Mast cells (MC) were identified by histochemistry and quantified. In EAO model, KF significantly reduced severity of histopathological testicular damage compared to rats in the vehicle group. KF also reduced the number of testicular MC compared to vehicle group. Similarly, in TCT model, multifocal damage of the contralateral testis was observed 30 days after testicular torsion characterized by sloughing of the germinal epithelium, seminiferous tubule atrophy, and interstitial edema. Focal signs of inflammation and fibrosis of seminiferous tubular walls were also observed. In contrast, sections of contralateral testis of rats injected with KF and killed 30 days after surgery showed normal histological features. A significant decrease in the number of MC was observed in rats treated with KF compared to untreated animals. In conclusion, we demonstrated that treatment with KF reduced testicular inflammatory process and MC infiltrates in both EAO and TCT models. The results suggest a promising treatment for infertile male patients with testicular pathologies associated with inflammation and germ cell loss.
Assuntos
Doenças Autoimunes/patologia , Epididimite/patologia , Antagonistas dos Receptores Histamínicos H1/farmacologia , Cetotifeno/farmacologia , Mastócitos/efeitos dos fármacos , Orquite/patologia , Torção do Cordão Espermático/patologia , Testículo/efeitos dos fármacos , Animais , Doenças Autoimunes/imunologia , Contagem de Células , Epididimo/efeitos dos fármacos , Epididimo/imunologia , Epididimo/patologia , Epididimite/imunologia , Hipersensibilidade Tardia , Imunidade Celular/efeitos dos fármacos , Masculino , Mastócitos/imunologia , Mastócitos/patologia , Orquite/imunologia , Ratos , Índice de Gravidade de Doença , Torção do Cordão Espermático/imunologia , Testículo/imunologia , Testículo/patologia , VacinaçãoRESUMO
AIM: The mechanism by which unilateral testicular torsion leads to injury of the contralateral testis is still controversial. The present study aimed to evaluate immunohistopathological changes in the contralateral testis of rats after acute testicular torsion. METHODS: 40 pubertal rats were randomly divided into 3 groups. Group 1 (n=10) functioned as controls. Group 2 rats (n=10) underwent a sham operation, and Group 3 (n=20) underwent 720° torsion of the left spermatic cord (3 h) followed by detorsion (24 h). RESULTS: Immunofluorescence tests were done to investigate contralateral lesions in half of the animals in Group 3. Nitro blue tetrazolium (NBT) was injected in both testes to identify the presence of oxygen-derived free radicals. 24 h after reperfusion, bilateral samples of the testes were obtained for histological analysis. Fisher's exact test was used for statistical analysis with p-values <0.05 considered significant.Immunofluorescence tests were positive for the contralateral (right) testis but with a lower intensity than that of the testis submitted to torsion. NBT reaction was intense all over the left testis while a minor reaction was visible in the right testis. In Group 3 the left distorted testicle showed diffuse edema with cell elimination and extensive necrosis of the seminiferous tubules. Histological lesions were moderate to mild in the contralateral testis. CONCLUSION: An autoimmune IgG-mediated mechanism deposited on the basement membrane of seminiferous tubules seems to be involved in the genesis of contralateral testis injury.
Assuntos
Autoimunidade , Torção do Cordão Espermático/imunologia , Testículo/imunologia , Doença Aguda , Animais , Anticorpos Anti-Idiotípicos/imunologia , Modelos Animais de Doenças , Seguimentos , Imunoglobulina G/imunologia , Imuno-Histoquímica , Masculino , Ratos , Ratos Wistar , Torção do Cordão Espermático/patologia , Testículo/patologiaRESUMO
In spite of prompt diagnosis and either orchiectomy or preservation of the affected testis, infertility remains a significant sequel to testicular torsion. The objective of this study was to evaluate the late endocrine profile, seminal parameters, and antisperm antibody levels after testicular torsion. We also analyzed the impact of orchiectomy or detorsion on the organ fate. Of 24 patients evaluated after testicular torsion, 15 were treated with orchiectomy (group 1) and 9 were treated with orchiopexy (group 2). All subjects were assessed by semen analysis, endocrine profile (levels of follicle-stimulating hormone, luteinizing hormone, and testosterone), and seminal antisperm antibody levels. A group of 20 proven fertile men was used as the control. Median ischemia time in group 1 (48 hours) was significantly higher than in group 2 (7 hours). Both groups demonstrated decreases in sperm count and morphology compared with controls. Group 1 showed a significantly higher motility than group 2 (P = .02). Group 1 also showed a significantly better morphology by World Health Organization and Kruger criteria than group 2 (P = .01). All patients presented endocrine profiles within the normal range, and no significant differences in antisperm antibody levels were detected between the groups. However, a trend for higher levels was found in patients treated for testicular torsion, regardless of the fate of the testis. Moreover, no significant correlation was found between antisperm antibody levels and age at torsion, ischemia time, seminal parameters, or treatment applied. In conclusion, we found that after torsion patients maintain late hormonal levels within the normal range. Testicular fate did not have any correlation with the formation of antisperm antibodies. Although sperm quality was preserved in most of the patients with the exception of sperm morphology, patients treated with orchiectomy presented better motility and morphology compared with the detorsion group. Further studies may clarify whether maintenance of a severely ischemic testicle may impair testicular function.
Assuntos
Autoanticorpos/sangue , Sêmen/fisiologia , Torção do Cordão Espermático/cirurgia , Espermatozoides/imunologia , Testículo/cirurgia , Adolescente , Adulto , Hormônio Foliculoestimulante/sangue , Lateralidade Funcional , Humanos , Hormônio Luteinizante/sangue , Masculino , Orquiectomia , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Torção do Cordão Espermático/sangue , Torção do Cordão Espermático/imunologia , Testosterona/sangueRESUMO
As atividades testiculares, hormonal e espermiogênica säo de extrema importância para o homem e para a manutençäo e o aprimoramento da humanidade. Trauma, tumores, varicocle, criptorquidia, anorquia, atrofias, torçäo de cordäo espermático, estäo entre as diversas causas da infertilidade masculina. A integridade da barreira testículo - sangüínea parece ter um papel fundamental na patôgenese da orquite auto-imune. A orquite auto-imune é um processo inflamatório testicular mediado por formaçäo de anticorpos, contra os próprios antígenos testiculares do indivíduo, causando lesöes no epitélio germinativo. Neste estudo foram utilizados oitenta (80) ratos Wistar, singênicos, machos, adultos, separados em dez grupos, submetidos à torçäo unilateral do testículo, sob anestesia, por um período de duas à doze horas, seguido, entäo, de destorçäo e exame anatomopatológico das gônadas contralateral e ipsilateral, em períodos que variaram de duas à dez semanas. Estes testículos foram analisados através das técnicas de histologia e de imunofluorescência com a utilizaçäo de anticorpos monoclonais para as imunoglobulinas IgA, IgG e IgM de coelho e cabra, contra os antígenos testiculares do rato, para que se estudasse as possíveis alteraçöes no tecido testicular do animal, objetivando a comprovaçäo da existência de complexos auto-imunes no epitélio germinal. O estudo demonstrou a presença de imunoglobulinas, principalmente das classes IgG e IgM na luza e no interstício dos túbulos semíferos. Alteraçöes estruturais do testículo contralateral, näo torcido, foram demonstradas. Os resultados deste experimento indicam que o sistema inume de animais sadios contém linfócitos com receptores para os próprios antígenos, capazes de, na torçäo unilateral do cordäo espermático, promoverem uma doença auto-imune. A utilizaçäo de substâncias imuno-supressoras, neste estudo, o corticóide, foi feita para tentar minimizar ou mesmo coibir o processo auto-agressivo. Existiu uma proteçäo testicular contralateral efetiva, com o uso precoce da referida droga. É sugerido que a permanência de um testículo necrótico na bolsa escrotal, após torçäo prolongada, pode levar à subfertilidade ou infertilidade.