Quercetin Inhibits ROS-p53-Bax-caspase-3 axis of apoptosis and augments gonadotropin and testicular hormones in chronic unpredictable stress-Induced testis injury / La quercetina inhibe el eje de apoptosis ROS-p53-Bax-caspasa-3 y aumenta la gonadotropina y las hormonas testiculares en la lesión testicular inducida por estrés crónico e impredecible

SUMMARY: A large body of evidence supports the protective role of the flavonol antioxidant compound quercetin in mammals. We tested the hypothesis that quercetin can protect against the hypothalamus-pituitary-gonadal (HPG) axis defect like a reduction in gonadotropins and testicular hormones and abnormal semen analysis induced by chronic unpredictable stress (CUS), possibly via the downregulation of oxidative stress (ROS) and p53-Bax-caspase-3 pathways. Rats were either exposed to a variety of unpredictable stressors daily before being sacrificed after 3 weeks (model group) or were treated with quercetin (50 mg/kg body weight/day) at the same time the CUS were induced (treated group). Harvested testicular tissues were stained with basic histological staining, and testis homogenates were assayed for the tumor suppressor p53, apoptosis regulator Bax, B-cell lymphoma 2 (Bcl-2), caspase-3, malondialdehyde (MDA), glutathione peroxidase (GPx), and superoxide dismutase (SOD). In addition, harvested epididymis tissues were used to assess semen analysis, and blood samples were assayed for the testicular hormone testosterone, the adrenal cortex hormone corticosterone, and the anterior pituitary gonadotropins, follicular stimulating hormone (FSH) and luteinizing hormone (LH). CUS induced profound testicular damage and significantly (p<0.05) induced p53, Bax, caspase-3, MDA, and corticosterone, which were significantly (p<0.05) inhibited by quercetin except corticosterone. Whereas, quercetin significantly (p<0.05) increased FSH, LH, testosterone, Bcl-2, GPx, and SOD levels that were inhibited by CUS. In addition, CUS induced oligozoospermia, asthenozoospermia, and teratozoospermia, which were significantly (p<0.05) protected by quercetin. Thus, Quercetin protects against CUS-induced HPG defects in rats, which is associated with the inhibition of ROS-p53-Bax-caspase-3 axis.

RESUMEN: El papel protector del compuesto antioxidante flavonol quercetina en los mamíferos ha sido ampliamente reportado. Probamos la hipótesis que la quercetina puede proteger contra el defecto del eje hipotálamo-hipofisiario- gonadal (HHG) como una reducción de gonadotropinas y hormonas testiculares y análisis de semen anormal inducido por estrés crónico impredecible (ECI), posiblemente a través de la regulación reducida del estrés oxidativo (REO) y las vías p53- Bax-caspasa-3. Las ratas fueron expuestas a una variedad de fac- tores estresantes impredecibles diariamente antes de ser sacrificadas después de 3 semanas (grupo modelo) o fueron tratadas con quercetina (50 mg / kg de peso corporal / día) al mismo tiempo que se indujo la ECI (grupo tratado). Los tejidos testiculares fueron teñidos con tinción histológica básica y los homogeneizados de testículo se analizaron para determinar el supresor de tumores p53, el regulador de apoptosis Bax, el linfoma de células B 2 (Bcl-2), la caspasa-3, el malondialdehído (MDA), la glutatión peroxidasa (GPx) y superóxido dismutasa (SOD). Además, se utilizaron tejidos del epidídimo recolectados para evaluar el análisis de semen y se analizaron muestras de sangre para determinar la hormona testicular testosterona, la hormona corticosterona de la corteza suprarrenal y las gonadotropinas de la hipófisis anterior, la hormona estimulante folicular (FSH) y la hormona luteinizante (LH). El ECI indujo daño testicular importante e indujo significativamente niveles de (p <0,05) p53, Bax, caspasa-3, MDA y corticosterona, que fueron inhibidos (p <0,05) por la quercetina. La quercetina aumentó significativamente (p <0,05) los niveles de FSH, LH, testosterona, Bcl-2, GPx y SOD que fueron inhibidos por ECI. Además, ECI indujo oligozoospermia, astenozoospermia y teratozoospermia, protegidos de manera significativa (p <0,05) por la quercetina. Por lo tanto, la quercetina protege contra los defectos de HHG inducidos por ECI en ratas, lo que está asociado con la inhibición del eje ROS-p53-Bax-caspasa-3.

Effects of testicular dysgenesis syndrome components on testicular germ cell tumor prognosis and oncological outcomes

ABSTRACT Purpose: To evaluate whether components of Testicular Dysgenesis Syndrome (TDS) affect testicular germ cell tumor (TGCT) prognosis and oncological outcomes. According to the hypothesis called TDS; undescended testis, hypospadias, testicular cancer and spermatogenic disorders share the same risk factors and have a combined fetal origin. Materials and Methods: We retrospectively evaluated the stages and oncological outcomes of 69 patients who underwent radical orchiectomy between January 2010 and December 2014 due to TGCT in our department. The presence of undescended testis, hypospadias and semen parameters disorders were recorded according to anamnesis of patients. Results: Among 69 patients with TGCT, only 16 (23.1%) had TDS. Significantly higher rate of TDS (36.1% vs. 9.1%) was observed at the advanced stages of TGCT(p=0.008). In the TDS group, the rates of local recurrence (50% vs. 11.3%, p<0.001), distant metastasis (93.6% vs. 3.8%, p<0.001) and cancer-spesific mortality (87.5% vs. 3.8%, p<0.001) were found significantly higher than those without TDS. The predicted time for recurrence-free survival (13.70±5.13 vs. 100.96±2.83 months, p<0.001) metastasis-free survival (13.12±4.21 vs. 102.79±2.21 months, p <0.001) and cancer-specific survival (13.68±5.38 vs. 102.80±2.19 months, p<0.001) were also statistically lower in this group. Conclusions: According to our preliminary results, there is an apparent relationship between TDS and tumor prognosis. Even if the components of TDS alone did not contain poor prognostic features for TGCT, the presence of TDS was found as the most important independent predictive factor for oncological outcomes in both seminomas and nonseminomas as well as all patients with TGCT.

Cocaine abuse that presents with acute scrotal pain and mimics testicular torsion

ABSTRACT Report case (s) relevant aspects: Man, 27 years old, complaining of acute testicular pain by 2 hours in the remaining left testicle. Denies fever, lower urinary tract symptoms such as dysuria, urinary frequency, concommitant or prior urethral discharge to the painful condition. He underwent right orchiectomy 13 years ago by testicular torsion. He is a chronic user of cocaine for 15 years and during the last three days the drug use was continuous and intense. Proposed premise substantiating case (s) description: Initial diagnostic hypothesis: Syndromic: Acute Scrotum Syndrome (SEA) Main Etiologic (testicular torsion) Secondary Etiologic (acute orchiepididymitis) Briefly delineates what might it add? Lines of research That Could be Addressed: In this challenging clinical case we presented an alternative and new etiologic diangosis for the acute scrotum which the main etiologic factor remains testicular torsion. This new diangosis is acute testicular ischemia as a complication of cocaine abuse.

La lepra y el testículo / Leprosy and the testis

Introducción. La afección testicular es frecuente en la lepra lepromatosa, daño que se incrementa cuando cursa con eritema nudoso leproso. Objetivo. Presentar un paciente con lepra lepromatosa y eritema nudoso leproso con grave compromiso testicular. Materiales y métodos. Se estudió un hombre de 28 años con lepra lepromatosa desde los 22, que durante la poliquimioterapia para la lepra presentó eritema nudoso leproso crónico que afectó ambos testículos y no respondió al manejo convencional. El dolor persistente obligó a practicar orquidectomía izquierda. Resultados. Este testículo presentaba atrofia tubular y fibrosis notorias, conglomerados de macrófagos espumosos, sin bacilos, hiperplasia focal de células de Leydig, endarteritis y arteritis linfocitaria y granulomatosa de vasos pequeños y medianos; estos cambios también estaban presentes en el epidídimo. Un estudio llevado a cabo dos años después de terminar su tratamiento y de la orquidectomía izquierda, demostró azoospermia, testosterona total normal, testosterona libre discretamente disminuida y hormonas lutropina (luteinizante) y folitropina (estimulante del folículo) elevadas. No había disminución de la libido ni de su actividad sexual. Se revisaron los conceptos generales sobre el eritema nudoso leproso y las alteraciones que la lepra produce en el testículo. Conclusión. La lepra lepromatosa puede conducir a hipogonadismo. Los programas de lepra deben contemplar esta complicación para corregir y evitar sus secuelas.

Introduction. Damage of testicles is frequent in lepromatous leprosy and worsened by the presence of erythema nodosum leprosum. Objective. A patient is presented who developed lepromatous leprosy and erythema nodosum leprosum with major testicular compromise. Material and methods. The 28-year-old male patient had lepromatous leprosy since age 22. During a polychemotherapy treatment for the lepromatous leprosy, he presented chronic erythema nodosum leprosum that affected both testicles; he did not respond to the conventional treatment. A left orchidectomy was performed to treat the persistent pain. Results. The extracted testis evidenced the following: tubular atrophy, extensive fibrosis, cumulus of foamy macrophages without rods, focal Leydig cell hyperplasia, linfocitary and granulomatous arteritis and endarteritis of small and medium size vessels. These changes were also observed in the epididymis. Two years after the polychemoterapy and the orchidectomy, the patient exhibited azoospermy, normal total testosterone, slightly diminished free testosterone and elevated levels of luteinizing hormone and follicle-stimulating hormone. No loss of libido or sexual activity was reported. General concepts of erythema nodosum leprosum were reviewed, as well as the pathologic changes produced by leprosy in the testis. Conclusion. Lepromatous leprosy may lead to hypogonadism. This condition is recommended for inclusion in leprosy diagnostic programs in order to detect and treat the consequences of the possible hypogonadism.

Splenogonadal fusion and testicular cancer: case report and review of the literature / Fusão esplenogonadal e câncer testicular: relato de caso e revisão da literatura

A 36 year-old man after tests for assessing male infertility was diagnosed with primary infertility, bilateral cryptorchidism, nonobstructive azoospermia and discontinuous splenogonadal fusion. Carcinoma in situ was found in his left testicle, which was intraabdominal and associated with splenogonadal fusion. To our knowledge, this is the fourth case of splenogonadal fusion associated with testicular cancer reported. One should always bear in mind the possibility of this association for the left cryptorchid testicle.

Um homem de 36 anos, depois de ser submetido a exames para avaliação de infertilidade masculina, foi diagnosticado com infertilidade masculina primária, criptorquidia bilateral, azoospermia não obstrutiva e fusão esplenogonadal descontínua. Carcinoma in situ estava presente no testículo esquerdo, que tinha localização intra-abdominal e estava associado à fusão esplenogonadal. Esse é o quarto caso de fusão esplenogonadal associada a câncer testicular, segundo nossa avaliação. Deve-se sempre ter em mente a possibilidade dessa associação em testículos criptorquídicos à esquerda.

Prospective study on the effects of a polypropylene prosthesis on testicular volume and arterial flow in patients undergoing surgical correction for inguinal hernia

PURPOSE: To evaluate testicular volume and arterial flow in patients undergoing surgical correction for inguinal hernia, with polypropylene prosthesis. METHODS: This was an observational prospective clinical study on 39 male patients with unilateral inguinal hernia of types III A and III B according to the Nyhus classification who underwent surgical correction with implantation of a polypropylene prosthesis by means of the Lichtenstein technique. The patients were evaluated using Doppler ultrasound before the operation and selectively at the third and sixth months after the operation. The variables studied were testicular volume, systolic and diastolic velocity, resistance index and pulsatility index. RESULTS: No statistically significant alterations in the variables studied were observed over the course of time: testicular volume (p= 0.197); systolic velocity (p= 0.257); diastolic velocity (p= 0.554); resistance index (p= 0.998); and pulsatility index (p= 0.582). CONCLUSION: No alteration in testicular volume and arterial flow over a six-month period was observed among patients who underwent surgical correction for inguinal hernia using a polypropylene prothesis.

OBJETIVO: Avaliar o volume testicular e o fluxo na artéria testicular em pacientes operados de inguinal com prótese de polipropileno. MÉTODOS: Estudo clínico prospectivo observacional em 39 pacientes do sexo masculino portadores de hérnia inguinal tipo III A e III B na classificação de Nyhus os quais foram submetidos a hernioplastia inguinal com implantação de prótese de polipropileno com a técnica de Lichtenstein. Os pacientes foram avaliados com ultra-sonografia Doppler no pré-operatório; no 3° mês e no 6° mês de pós-operatório. As variáveis estudadas foram: volume testicular; velocidade sistólica e diastólica, o índice de resistividade e o índice de pulsatilidade. RESULTADOS: Não se observou alterações estatisticamente significantes nas variáveis ao longo do tempo: volume testicular (p=0,197); velocidade sistólica (p=0,257); velocidade diastólica (p=0,554); índice de resistividade (p=0,998); índice de pulsatilidade (p=0,582). CONCLUSÃO: Não se observou alteração no volume testicular e no fluxo sanguíneo da artéria testicular após seis meses nos pacientes submetidos à correção cirúrgica de hérnia inguinal com prótese de polipropileno..

Fluxión funiculotesticular, una complicación frecuente en la herniorrafia inguinal / Spermatic cord and testicular swelling as a complication of inguinal hernia repair

El presente estudio presenta a la fluxión funiculotesticular (FFT) como la complicación más frecuente de la herniorrafia inguinal, destacando que es poco mencionada en publicaciones sobre el tema a nivel internacional. El objetivo del presente estudio es dar a conocer la frecuencia de esta complicación en los pacientes intervenidos en el Centro de Referencia de Salud (CRS) Cordillera, analizar sus manifestaciones clínicas y su etiopatogenia. El estudio observacional, descriptivo, prospectivo se realizó en 304 varones portadores de hernia inguinal derivados desde los consultorios de las comunas de Peñalolén y Macul al CRS Cordillera Oriente. Los pacientes fueron intervenidos consecutivamente con anestesia local y técnicas quirúrgicas estándar y en forma ambulatoria. El control postoperatorio lo realizó un miembro del equipo quirúrgico a la semana y al mes de la intervención buscando dirigidamente signos de FFT. Ésta se encontró en 22 por ciento siendo severa en el 2,5 por ciento de los casos. Esta frecuencia fue similar para hernias directas e indirectas. La FFT fue significativamente mayor en las hernias recidivadas, las inguinoescrotales y en los casos en los que se instaló una malla. Esta complicación pone en evidencia una cadena de hechos que se inician con el trauma quirúrgico producto de la disección necesaria en una herniorrafia inguinal que produce inflamación, congestión venosa y linfática. En casos más graves puede producirse trombosis venosa y eventualmente daño isquémico del testículo.

Background: A complication of inguinal hernia repair that is seldom mentioned is spermatic cord and testicular swelling. Aim: To study the frequency of this complication, its clinical manifestations and to analyze its pathogenesis. Material and Methods: A descriptive observational, prospective study in 304 men (aged 15 to 89 years), subjected to an inguinal hernia repair. Operation was performed under local anesthesia in an ambulatory basis, with standard surgical techniques. The postoperative assessment was done by a member of the surgical staff one week and one month after surgery. Results: A mild or moderate swelling occurred in 19.5 percent of patients and a large, severe spermatic cord and testicular swelling developed in 2.5 percent of the cases. The frequency was similar in patients with direct or indirect hernias. Those with recurrent hernias, with hernias growing into the scrotum or that required a mesh for hernia repair, had a significantly higher frequency of spermatic cord and testicular swelling. No patient developed testicular ischemia. Conclusions: Spermatic cord and testicular swelling is the consequence of the dissection required for hernia repair, that is followed by a variable grade of damage to the tissues, inflammation, venous and lymphatic congestion and edema. In seldom occasions venous thrombosis and testicular damage may take place.

Role of testicular interleukin-1 alpha tIL-1alpha in testicular physiology and disease

This review focuses on the role of the cytokine interleukin-1a [IL-1a] in the testis; elaborating upon its importance during the complex process of spermatogenesis while relating this cytokine to some of the pathophysiological states affecting the testis. IL-1a, a proinflammatory cytokine, is expressed constitutively by the intact adult rat testis where it acts on germ, Sertoli and Leydig cells to regulate germ cell proliferation and steroidogenesis. The sequence identity of testicular IL-1a matches with the one secreted by activated macrophages in systemic immunity. The classical macrophage IL-1a is produced as 32 kDa precursor protein which is processed to mature 17 kDa IL-1a and a 16 kDa propiece. The rat testicular IL-1a, mainly secreted by Sertoli cells, was found to have molecular heterogeneity that can be observed both at the transcriptional and the translational levels. In the rat testis, two transcripts were found to be expressed with 941 bp and 767 bp [that lacks 174bp] which were translated into 32 kDa and 24 kDa precursor proteins, respectively. The 32 kDa precursor protein is processed to the 17 kDa mature IL-1a. Identical transcripts are also shown to be present in cat, dog and pig. Most of the functional role is assigned to the mature 17 kDa IL-1a isoform. However, functional analysis of recombinant rat IL-1a isoforms showed that there was a clear biopotency difference between these forms in order of 17 kDa IL-1a>32proIL-1a>24proIL-1a. Furthermore, the mature 17 kDa tIL-1a has also been implicated in pathologies such as orchitis, relapse of acute lymphoblastic leukemia [ALL] in the testis and infertility disorders in men. Thus, tIL-1a may play an important functional role both in coordination of normal testicular physiology as well as in contributing to the disease states in the testis

Traumatic testicular dislocation a review of 36 cases.

We retrospectively reviewed 36 patients who were treated in our institutes with traumatic testicular dislocation from 1975 to 1997. The mean patient age was 25 years old (18-38). Average time to present at the emergency room was 1 hour (0.5-6). Bilateral dislocation was found in thirty cases and unilateral dislocation was found in six cases. The sites of dislocation included: 34 cases (64 testes) at superficial inguinal area, one case (one testis) at acetabular area, and one case (one testis) at the perineal area. Closed reduction under general anesthesia was successful in 14 cases, open reduction after failed closed reduction in 10 cases, open exploration and repaired testis with reposition in 11 cases and orchiectomy only in one case. The overall results after treatment showed the normal size and position of the testis.

Microlitiasis testicular: presentación de un caso y revisión / Testicular microlithiasis: case presentation and review

La microlitiasis testicular es una patología rara, usualmente un hallazgo incidental, que ha cobrado mucha importancia diagnóstica en los últimos años por su asociación con un alto porcentaje de neoplasia testicular y una gran variedad de anormalidades genéticas y urológicas. Su diagnóstico es radiológico y puede confirmarse por histopatología. La ecografía revela múltiples lesiones puntiformes hiperecoicas con distribución difusa en el parénquima afectado. Histologicamente cosiste en la presencia de cálculos en los túbulos seminíferos. Presentamos un caso que destaca la apariencia sonográfica más comunmente encontrada en esta patología. Una radiografía y biopsia testicular confirmó la naturaleza calcificada de las lesiones. Este constituye el primer caso reportado por la literatura nacional

The mechanism of low testosterone levels in homozygous sickle-cell disease

Significantly lower testosterone levels are common in male patients with homozygous sickle-cell (SS) disease and have been attributed to either abnormalities of the hypothalamo-pituitary axis or primary testicular failure. The mechanism has now been investigated by observing the response to gonadrotropinthytotropin releasing hormones (GnRH-TRH) in 10 male patients with SS disease and in 10 matched male sibling controls without sickle-cell disease. Mean basal levels of luteninizing hormone (LH) follicular stimulating hormone (FSH) and thyrotropin (TSH) were significantly elevated but prolactin (RL) levels were within the normal range in the SS group. All hormones increased following GnRH-TRH, and proportionate increases over baseline were similar for FSH and TSH in SS and AA subjects, but SS patients showed a lesser percentage increase in LH at 30 minutes, and a higher percentage increase in PRL at 60 minutes. These observations are more consistent with primary testicular failure than with adnormalities of the hypothalmic-pituitaty-testiculat axis.

Adverse effects of vasectomy: sperm granuloma of epididymides.

Rats and mice were vasectomized to study the pathological changes in the development and resolution of vasectomy induced sperm granuloma. Epididymal weights were increased in all groups of vasectomized animals, whereas testicular weights did not change. Granuloma in the form of yellow nodular masses of cysts were present at the lower pole of the epididymis. It consisted of a pool of sperm and other material surrounded by a wall of histocytes or macrophages. The biologic significance of the phenomena has been discussed.