RESUMO
PURPOSE: To evaluate the morphological and stereological parameters of the testicles in mice exposed to bisphenol S and/or high-fat diet-induced obesity. MATERIAL AND METHODS: Forty adult male C57BL/6 mice were fed a standard diet (SC) or high-fat diet (HF) for a total of 12 weeks. The sample was randomly divided into 4 experimental groups with 10 mices as follows: a) SC - animals fed a standard diet; b) SC-B - animals fed a standard diet and administration of BPS (25 µg/kg of body mass/day) in drinking water; c) HF: animals fed a high-fat diet; d) HF-B - animals fed a high-fat diet and administration of BPS (25 µg/Kg of body mass/day) in drinking water. BPS administration lasted 12 weeks, following exposure to the SC and HF diets. BPS was diluted in absolute ethanol (0.1%) and added to drinking water (concentration of 25 µg/kg body weight/day). The animals were euthanized, and the testes were processed and stained with hematoxylin and eosin (H&E) for morphometric and stereological parameters, including density of seminiferous tubules per area, length density and total length of seminiferous tubules, height of the tunica albuginea and the diameter of the seminiferous tubules. The images were captured with an Olympus BX51 microscope and Olympus DP70 camera. The stereological analysis was done with the Image Pro and Image J programs. Means were statistically compared using ANOVA and the Holm-Sidak post-test (p<0.05). RESULTS: The seminiferous tubule density per area reduced in all groups when compared with SC samples (p<0.001): HF (40%), SC-B 3(2%), and HF-B (36%). Length density was reduced significantly (p<0.001) in all groups when compared with SC group: HF (40%), SC-B (32%), and HF-B (36%). The seminiferous tubule total length was reduced (p<0.001) when compared to f HF (28%) and SC-B (26%) groups. The tubule diameter increased significantly (p<0.001) only when we compared the SC group with SC (54%) an SC-B (25%) groups and the tunica thickness increased significantly only in HF group (117%) when compared with SC-B (20%) and HF-B 31%. CONCLUSION: Animals exposed to bisphenol S and/or high-fat diet-induced obesity presented important structural alterations in testicular morphology.
Assuntos
Compostos Benzidrílicos , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Obesidade , Fenóis , Testículo , Masculino , Animais , Dieta Hiperlipídica/efeitos adversos , Testículo/efeitos dos fármacos , Testículo/patologia , Fenóis/toxicidade , Obesidade/induzido quimicamente , Distribuição Aleatória , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/patologia , Modelos Animais de Doenças , Camundongos , Reprodutibilidade dos Testes , SulfonasRESUMO
El ácido valproico (VPA) es un fármaco antiepiléptico teratógenico que, al ser administrado durante etapas tempranas del embarazo, puede producir alteraciones en el desarrollo embriofetal, las que se manifiestan tanto a nivel del sistema nervioso como del testículo. No obstante, se ha reportado que la administración de vitamina E (VE) podría revertir dichas alteraciones. El objetivo del presente estudio fue determinar el efecto protector de la VE a nivel testicular en fetos y ratones púberes expuestos a VPA durante la fase embrionaria de su desarrollo. Se utilizó un total de 30 ratones hembra adultas gestantes (Mus musculus) cepa BALB/c, las cuales se dividieron en 6 grupos. El estudio contempló el análisis de fetos machos a los 17,5 días post-coital (dpc) y machos juveniles a las 6 semanas post-natal. A los grupos 1 y 4 se les administró 0,3 mL de solución fisiológica (grupos control para 17,5 dpc y 6 semanas postnatal, respectivamente). A los grupos 2 y 5 se les suministró la cantidad de 600 mg/kg de VPA (grupos VPA), en tanto que a los grupos 3 y 6 se les aplicó la misma dosis de VPA complementada con 200 UI de VE (grupos VPA+VE). Se describió la histología normal y patológica del compartimento peritubular del testículo. En los grupos VPA se evidenció una degeneración de la pared peritubular, y atrofia de túbulos seminíferos, así como exfoliación de las células germinales. Por el contrario, en los grupos VPA+VE tales signos no fueron observados y la morfología presentó aspecto normal solo con algunas alteraciones focales. Estos resultados corroboran el hecho que la administración de VE contrarresta en parte, los efectos deletéreos que ocasiona el VPA.
SUMMARY: Valproic acid (VPA) is a teratogenic antiepileptic drug that, when administered during the early stages of pregnancy, can produce alterations in embryo-fetal development, which manifest both at the level of the nervous system and the testicle. However, it has been reported that the administration of vitamin E (VE) could reverse these alterations. The study aimed to determine the protective effect of VE at the testicular level in fetuses and pubertal mice exposed to VPA during the embryonic phase of their development. 30 pregnant adult female mice (Mus musculus) BALB/c strain were used, which were divided into 6 groups. The study included the analysis of male fetuses at 17.5 days post-coital (dpc) and juvenile males at 6 weeks post-natal. Groups 1 and 4 were administered 0.3 mL of physiological solution. Groups 2 and 5 were given 600 mg/kg of VPA (VPA groups), while groups 3 and 6 were given the same dose of VPA supplemented with 200 IU of VE (VPA+VE). The normal and pathological histology of the peritubular compartment of the testis was described. In the VPA groups, degeneration of the peritubular wall, and atrophy of the seminiferous tubules, as well as exfoliation of the germ cells, were evident. On the contrary, in the VPA+VE groups such signs were not observed and the morphology presented a normal appearance with only some focal alterations. These results corroborate the fact that the administration of VE partially counteracts the deleterious effects caused by VPA.
Assuntos
Animais , Feminino , Gravidez , Camundongos , Testículo/efeitos dos fármacos , Vitamina E/administração & dosagem , Ácido Valproico/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Túbulos Seminíferos/citologia , Túbulos Seminíferos/efeitos dos fármacos , Testículo/citologia , Vitamina E/farmacologia , Camundongos Endogâmicos BALB C , Anticonvulsivantes/toxicidadeRESUMO
Cyclophosphamide (CP)-which is used to treat autoimmune diseases and cancer-is related to gonadotoxicity attributed to oxidative stress. As phycobiliproteins (PBPs) are strong antioxidants that are unexplored as protective agents against male gonadotoxicity, our work aimed to investigate the effects of PBP crude extract on testicular damage and sperm parameter alterations caused by CP in mice. Three doses of PBP (50, 100, and 200 mg/kg) were tested in the experimental groups (n = 8 per group), administered concomitantly with 100 mg/kg CP. After 42 days receiving PBP daily and CP weekly, body and relative testicular weights, serum testosterone levels, testicular lipoperoxidation and antioxidant enzyme activity levels, and testicular histology and sperm parameter alterations were assessed. The results showed that PBP crude extract at 200 mg/kg prevented testosterone serum reduction, body weight loss, lipoperoxidation and enzyme activity increments, and sperm parameter alterations and partially ameliorated relative testicular weight reductions and histological damage in CP-treated mice. In conclusion, we showed that PBP crude extract (200 mg/kg) mitigated oxidative damage in the testes and ameliorated alterations in sperm parameters in mice treated with CP (100 mg/kg); therefore, PBP extract could be considered as a potential protective agent against CP toxicity.
Assuntos
Ciclofosfamida/farmacologia , Ciclofosfamida/uso terapêutico , Ficobiliproteínas/toxicidade , Animais , Antioxidantes/farmacologia , Peso Corporal , Modelos Animais de Doenças , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/patologia , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/patologia , Testosterona/sangueRESUMO
Studies in laboratory animals have shown that male offspring from dams, exposed to nicotine during pregnancy and postnatal periods, show alterations in fertility, although the origin of this is still uncertain. In this study, we examined in a mouse model if the process of gonocyte maturation to spermatogonia was affected in male offspring from dams with nicotine administration during pregnancy and postnatal periods. BALB/C mice, with and without nicotine administrations in pregnancy and postnatal periods, were studied. The animals were euthanized at 3, 7, 10, 16, and 35 days postpartum (dpp). Testicular tissue samples were processed for histological, ultrastructural, and immunohistochemical studies; and testicular lipoperoxidation was determined. It was observed that in the nicotine-exposed animals, there was increased apoptosis and a reduction in the number of gonocytes that matured to spermatogonia. This gonocyte-spermatogonia maturation reduction was associated with a greater immunoreactivity to nicotinic acetylcholine receptors in the germ cells. Lipoperoxidation was similar in both groups until 16 dpp, with significant reduction at 35 dpp. Our findings suggest that nicotine intake during pregnancy and postnatal periods can affect the process of maturation of gonocytes to spermatogonia and the pool of available spermatogonia for spermatogenesis.
Assuntos
Feto/patologia , Nicotina/toxicidade , Efeitos Tardios da Exposição Pré-Natal/patologia , Espermatogônias/patologia , Animais , Animais Recém-Nascidos , Cotinina/análise , Feminino , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos BALB C , Gravidez , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/patologia , Espermatogônias/efeitos dos fármacos , Testículo/patologiaRESUMO
SUMMARY: The aim of this study is to investigate the effects of Protocatechuic acid and Corchorus olitorius on streptozotocin (STZ) induced diabetic rat testis tissue. Randomly selected Wistar Albino rats were divided into five groups as; Diabetes Mellitus, Diabetes Mellitus treated with Corchorus Olitorus (STZ+CO), Diabetes Mellitus treated with Protacatechuic acid (STZ+PCA), Corchorus olitorius (CO), Protocatechuic acid (PCA) and Control. Diabetic model was generated by intraperitoneal injection of 60 mg/kg Streptozotosin. After 48 hours of the STZ injection, blood samples were collected from tail vein in order to measure blood glycose levels. Over 250 mg/dL accepted as diabetic subjets and fed with 250 mg/kg Corchorus olitorius or 20 mg/kg PCA by oral gavage for three weeks. At the end of the experiment, right testes were removed and fixed in 10 % neutral formaldehyde for paraffine embedding. Sections were stained by HE, Masson trichrome, PAS and TUNEL for microscopic evaluation. Control, PCA-only and Corchorus olitorius-only treated group testes tissues showed a normal tissue organization, when degeneration in seminiferous tubules, the vacuolization, seperations in spermatogenic cell series, outpouring of cell groups in the lumen, vesicular body formation, liquid accumulation in the interstitial region and edema were observed in STZ induced diabetic models and untreated groups. Besides, higher amount of TUNEL (+) stained cells were determined in STZ group. On the other hand, blood glucose level and number of TUNEL (+) stained cells were decreased as a result of PCA and Corchorus olitorius treatment. Because of the reduction of blood glucose level and apoptotic cell numbers, PCA and Corchorus olitorius decreace the complications of diabetes mellitus induced rat testis.
RESUMEN: El objetivo de este estudio fue investigar los efectos del ácido protocatéquico y Corchorus olitorius sobre el tejido testicular de rata diabética inducida por estreptozotocina (STZ). Las ratas Wistar Albino fueron seleccionadas al azar y se dividieron en cinco grupos; Diabetes Mellitus, Diabetes Mellitus tratada con Corchorus olitorius (STZ + CO), Diabetes Mellitus tratada con ácido protocatéquico (STZ + PCA), Corchorus olitorius (CO), ácido protocatéquico (PCA) y Control. El modelo diabético se generó por inyección intraperitoneal de 60 mg/kg de estreptozotosina. Después de 48 horas de la inyección de STZ, se recogieron muestras de sangre de la vena de la cola para medir los niveles de glucosa. Niveles mayores a 250 mg/dL fueron considerados como especímenes diabéticos y alimentados con Corchorus olitorius de 250 mg/kg o PCA de 20 mg/kg por sonda oral durante tres semanas. Al final del experimento, se extirparon los testículos derechos y se fijaron en formaldehído neutro al 10 % para la inclusión en parafina. Las secciones se tiñeron con HE, tricromo de Masson, PAS y TUNEL para evaluación microscópica. Los tejidos de los testículos de los grupos control, tratados solo con PCA y con Corchorus olitorius mostraron una organización tisular normal. En cambio en modelos diabéticos inducidos por STZ y grupos no tratados se observó degeneración en los túbulos seminíferos, vacuolización, separaciones en series de células espermatogénicas, efusión de grupos celulares en la luz, formación del cuerpo vesicular, acumulación de líquido en la región intersticial y edema. Además, se determinó una mayor cantidad de células teñidas con TUNEL (+) en el grupo STZ. Por otro lado, el nivel de glucosa en sangre y el número de células teñidas con TUNEL (+) disminuyeron como resultado del tratamiento con PCA y Corchorus olitorius. Debido a la reducción del nivel de glucosa en sangre y el número de células apoptóticas, se observó que PCA y Corchorus olitorius disminuyen las complicaciones de los testículos de rata inducidos por diabetes mellitus.
Assuntos
Animais , Masculino , Ratos , Testículo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Corchorus/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hidroxibenzoatos/farmacologia , Túbulos Seminíferos/efeitos dos fármacos , Glicemia/análise , Extratos Vegetais/uso terapêutico , Ratos Wistar , Hidroxibenzoatos/uso terapêuticoRESUMO
Several plant species such as Pfaffia glomerata are widely used in traditional Brazilian medicine as stimulants and aphrodisiacs. In this regard, the aim of our study was to explore the effects of the long-term intake of the hydro-alcoholic root extract of P glomerata on the germ and somatic cells within the seminiferous tubules in adult Balb/c mice. The experimental groups were placed as: controls (water and DMSO), and treated with 300 and 400 mg/kg of the root extract. The number of germ and somatic cells, the proportion of pathological seminiferous tubules, and the germ cell apoptotic levels were evaluated. The volume and proportion of the seminiferous epithelium was decreased after the extract intake due to the increased germ cell apoptotic levels. Vacuolization of Sertoli cell cytoplasm was observed widely in pathological tubules, along with fully disorganized epithelia, showing multinucleated cells, which lead to decreased daily sperm production. Taken together, our results indicate that long-term intake of the P glomerata caused deleterious effects on spermatogenesis by inducing apoptosis and altering the seminiferous tubule's epithelial dynamics.
Assuntos
Amaranthaceae/química , Extratos Vegetais/farmacologia , Epitélio Seminífero/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Células Germinativas/efeitos dos fármacos , Células Germinativas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Raízes de Plantas/química , Epitélio Seminífero/patologia , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/patologia , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/patologiaRESUMO
Studies with 6-n-propyl-2-thiouracil (PTU) in laboratory rodents have shown that transient neonatal hypothyroidism leads to increased Sertoli cell (SC) number, testis size and sperm production. However, scarce and inconclusive data are available for farm animals. In the present study, Piau pigs received PTU in a gel capsule containing 8 mg/kg of body weight for 14 weeks starting from the first week of age, whereas control animals received only the vehicle. Blood samples were collected during the experimental period for hormonal evaluation in the serum. The animals were orchiectomized at adulthood and had their testes used for histomorphometric analysis. Indicating that the PTU concentration used was effective in promoting hypothyroidism, PTU-treated pigs showed a 30% lower body weight and reduced thyroxine levels (p < 0.05) during the treatment period. At adulthood, the body weight was similar in both groups but, surprisingly, PTU-treated pigs showed 30% lower testis weight (p < 0.05). In general, treated pigs presented increased follicle-stimulating hormone levels, whereas testosterone levels tended to be lower from 9 to 23 weeks of age. No significant differences were observed for estradiol, Leydig cell volume and number, tubular diameter, SC number per gram of testis, SC efficiency and meiotic index. However, seminiferous tubule occupancy, total tubular length, SC number per testis, and daily sperm production per testis and per gram of testis (DSP/g/T) were significantly lower (p < 0.05) in PTU-treated pigs. Therefore, in contrast to laboratory rodents, our results showed that SC proliferation and DSP/g/T (spermatogenic efficiency) in Piau pigs is diminished by postnatal PTU treatment.
Assuntos
Antimetabólitos/toxicidade , Hipotireoidismo/patologia , Propiltiouracila/toxicidade , Células de Sertoli/patologia , Espermatogênese/efeitos dos fármacos , Espermatozoides/patologia , Animais , Animais Recém-Nascidos , Contagem de Células , Hipotireoidismo/induzido quimicamente , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/patologia , Masculino , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/patologia , Células de Sertoli/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , SuínosRESUMO
Paracetamol is a widely used medication during gestation and lactation periods for the treatment of pain and fever. Several studies have shown that exposure to paracetamol can increase the incidence of cryptorchidism and decrease testosterone production. Therefore, the present study aimed to evaluate if maternal treatment with paracetamol during gestation and gestation/lactation periods can alter reproductive and behavioral parameters in male offspring. Female Wistar rats were treated daily by gavage with water or paracetamol (350 mg/kg/day) during gestation (CTRG and PARG) or gestation/lactation periods (CTRGL and PARGL). There were significant differences in histomorphometry (increased volume and total length of the seminiferous tubules) and weight of testes (PARG group) and copulatory behavior and testosterone levels (PARG and PARGL groups) at PND 120. Therefore, the present study showed that maternal exposure to paracetamol has an impact on the reproductive system and sexual behavior of male adult offspring suggesting an impaired in sexual hypothalamic differentiation at the beginning of the development of the brain.
Assuntos
Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Reprodução/efeitos dos fármacos , Animais , Feminino , Hipotálamo/efeitos dos fármacos , Hipotálamo/crescimento & desenvolvimento , Masculino , Troca Materno-Fetal , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Ratos Wistar , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/crescimento & desenvolvimento , Comportamento Sexual Animal/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/crescimento & desenvolvimento , Testosterona/sangueRESUMO
Hypoxia hypobaric (HH) can cause alterations at testicular level, with temperature increase, intrascrotal alteration and deterioration of spermatogenesis. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ketoprofen have anti-angiogenic properties, and can decrease testicular abnormalities. The objective of the study was to evaluate the effect of ketoprofen on spermatogenesis of mice exposed to continuous hypobaric hypoxia. 78 Mus musculus CF-1 male mice 3 to 4 months old were used and subjected to HH in chamber at 4200 m. They were divided into 13 groups (G) of 6 animals: 10 with HH cycles (1, 2, 3, 4 and 8, lasting 8.3 days each cycle, two groups each) and 3 in normoxia (Nx). Intraperitoneal ketoprofen 25 mg/kg was administered every 4 days. Euthanasia of these animals was performed at the end of each cycle and in the case the Nx groups at the end of cycles 1, 4 and 8. Percentage of microhematocrit and reticulocytes were measured in blood smears and a morphometric and histopathological analysis of the height of the epithelium, the tubular diameter and the diameter of the tubular lumen was made. It was shown that hematocrit increases continuously up to 8 cycles, while reticulocytes increase up to 3 cycles. Continuous HH decreases the tubular diameter in a sustained manner and proportional to HH cycles, and the height increased only in the groups subjected to 8 cycles. The groups treated with ketoprofen saw a decrease in angiogenesis, presenting some degree of protection at the testicular level.
La hipoxia hipobárica (HH) puede provocar alteraciones a nivel testicular, con aumento de la temperatura, alteración intraescrotal y deterioro de la espermatogénesis. Los antiinflamatorios no esteroidales (AINEs) como el ketoprofeno tienen propiedades antiangiogénicas, pudiendo disminuir las alteraciones testiculares. El objetivo de estudio fue evaluar el efecto del ketoprofeno en la espermatogénesis de ratones expuestos a hipoxia hipobárica continua. Se utilizaron 78 ratones macho Mus musculus CF-1 de 3 a 4 meses de edad y se sometieron a HH en cámara a 4200 m. Se dividieron en 13 grupos (G) de 6 animales: 10 con ciclos de HH (1, 2, 3, 4 y 8, con duración de 8,3 días cada ciclo, dos grupos cada uno) y 3 en normoxia (Nx). Se administró ketoprofeno intraperitoneal 25 mg/kg cada 4 días. La eutanasia de estos animales se realizó al final de cada ciclo y en el caso los grupos Nx al final de los ciclos 1, 4 y 8. Se midió porcentaje de microhematocrito y reticulocitos en frotis de sangre y se hizo un análisis morfométrico e histopatológico de la altura del epitelio, el diámetro tubular y el diámetro de la luz tubular. Se evidenció que el hematocrito aumenta de manera continua hasta los 8 ciclos, en cambio los reticulocitos aumentan hasta los 3 ciclos. La HH continua disminuye el diámetro tubular de forma sostenida y proporcional a los ciclos de HH, y la altura aumentó sólo en los grupos sometidos a 8 ciclos. Los grupos tratados con ketoprofeno se vio una disminución de la angiogénesis, presentando algún grado de protección a nivel testicular.
Assuntos
Animais , Masculino , Camundongos , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/farmacologia , Cetoprofeno/farmacologia , Hipóxia/fisiopatologia , Reticulócitos/efeitos dos fármacos , Túbulos Seminíferos/efeitos dos fármacos , Testículo/lesões , Anti-Inflamatórios não Esteroides/administração & dosagem , Cetoprofeno/administração & dosagem , Hematócrito , Neovascularização PatológicaRESUMO
OBJECTIVES: This study aimed to investigate the 'Cytoprotective effect of Lawsonia inermis aqueous leaf-extract on aluminium-induced Oxidative stress in Histomorphometric of the Seminiferous tubule and Stereology of Germ Cells of adult male Wistar rats', assessing its effect on the Histomorphometry of the Seminiferous tubule and Stereology of Germ Cells. METHODS: Thirty-five adult male Wistar rats, weighing between 100-196g, and fifteen mice of the same weight range were used. Lawsonia inermis extracts and aluminum chloride (AlCl3) were administered for a period of three (3) weeks, with Five (5) rats per group. Group 1 (control), received rat pellets and distilled water. Group 2 received 60mg/kg/d aqueous extract. Group 3 received 0.5mg/kg/d of AlCl3. Group 4 received 0.5mg/kg/d of AlCl3 and 60mg/kg/d of aqueous extract orally. Group 5 received 0.5mg/kg/d of AlCl3 and 75mg/kg/d of aqueous extract orally. Group 6 received 0.5mg/kg/d of AlCl3 and 100mg/kg/d of aqueous extract orally. Group 7 received 0.5mg/k/d of AlCl3 and 5mg/Kg/d of ascorbic acid orally. Twenty-four hours after the last administration, the animals were weighed, sedated with chloroform and blood was collected. The testes were removed and weighed. RESULTS: There were statistically significant changes in the percentage of seminiferous tubular and seminiferous ductal diameter within the experimental animals in all the groups (p<0.05). Stereological findings revealed increase in spermatogonia, primary spermatocytes, round Spermatids and elongated spematids, spermatozoa, Sertoli cells population of the control rats while the rats given 0.5mg of aluminum chloride per kg of body weight had the lowest value (p<0.05). CONCLUSION: In this study, we demonstrated the affected histomorphometry of the seminiferous tubule and stereology of germ cells in testes, where stress impacts were most felt and subsequently translated into drastic reproductive dysfunction and distortion of spermatogenesis.
Assuntos
Alumínio/toxicidade , Lawsonia (Planta) , Extratos Vegetais/farmacologia , Túbulos Seminíferos , Espermatozoides , Animais , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Túbulos Seminíferos/citologia , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/patologia , Espermatozoides/citologia , Espermatozoides/efeitos dos fármacos , Testículo/citologia , Testículo/efeitos dos fármacos , Testículo/patologiaRESUMO
The selective serotonin reuptake inhibitor fluoxetine has been used for the treatment of depression. Although sexual disorders have been reported in male patients, few studies have demonstrated the fluoxetine effect on the reproductive histophysiology, and the target of this antidepressant in testes is unknown. We evaluated the impact of short-term treatment with fluoxetine on the adult rat testes, focusing on steroidogenesis by Leydig cells (LC) and androgen-dependent testicular parameters, including Sertoli cells (SC) and peritubular myoid cells (PMC). Since UCHL1 (ubiquitincarboxyl-terminal hydrolase L1) seems to control spermatogenesis, the immunoexpression of this hydrolase was also analyzed. Adult male rats received 20 mg/kg BW of fluoxetine (FG) or saline (CG) for eleven days. In historesin-embedded testis sections, the seminiferous tubule (ST) and epithelial (Ep) areas, and the LC nuclear diameter (LCnu) were measured. The number of abnormal ST, androgen-dependent ST, SC and PMC was quantified. Testicular ß-tubulin levels and peritubular actin immunofluorescence were evaluated. Serum testosterone levels (STL) and steroidogenesis by 17ß-HSD6 immunofluorescence were analyzed, and either UCHL1-immunolabeled or TUNEL-positive germ cells were quantified. In FG, abnormal ST frequency increased whereas ST and Ep areas, androgen-dependent ST number, LCnu, 17ß-HSD6 activity and STL reduced significantly. TUNEL-positive PMC and SC was related to decreased number of these cells and reduction in peritubular actin and ß-tubulin levels. In FG, uncommon UCHL1-immunoexpression was found in spermatocytes and spermatids, and the number of UCHL1-immunolabeled and TUNEL-positive germ cells increased in this group. These findings indicate that LC may be a fluoxetine target in testes, impairing PMC-SC integrity and disturbing spermatogenesis. The increase of UCHL1 in the damaged tubules associated with high incidence of cell death confirms that this hydrolase regulates germ cell death and may be controlled by androgens. The fertility in association with the androgenic status of patients treated with fluoxetine should be carefully evaluated.
Assuntos
Androgênios/metabolismo , Morte Celular/efeitos dos fármacos , Fluoxetina/farmacologia , Células Germinativas/efeitos dos fármacos , Túbulos Seminíferos/efeitos dos fármacos , Ubiquitina Tiolesterase/metabolismo , Animais , Células Germinativas/metabolismo , Hidrolases/efeitos dos fármacos , Hidrolases/metabolismo , Marcação In Situ das Extremidades Cortadas/métodos , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Masculino , Ratos , Túbulos Seminíferos/metabolismo , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/metabolismo , Ubiquitinas/metabolismoRESUMO
Methamidophos (MET) is an organophosphate (OP) pesticide widely used in agriculture in developing countries. MET causes adverse effects in male reproductive function in humans and experimental animals, but the underlying mechanisms remain largely unknown. We explored the effect of MET on mice testes (5â¯mg/kg/day/4â¯days), finding that this pesticide opens the blood-testis barrier and perturbs spermatogenesis, generating the appearance of immature germ cells in the epididymis. In the seminiferous tubules, MET treatment changed the level of expression or modified the stage-specific localization of tight junction (TJ) proteins ZO-1, ZO-2, occludin, and claudin-3. In contrast, claudin-11 was barely altered. MET also modified the shape of claudin-11, and ZO-2 at the cell border, from a zigzag to a more linear pattern. In addition, MET diminished the expression of ZO-2 in spermatids present in seminiferous tubules, induced the phosphorylation of ZO-2 and occludin in testes and reduced the interaction between these proteins assessed by co-immunoprecipitation. MET formed covalent bonds with ZO-2 in serine, tyrosine and lysine residues. The covalent modifications formed on ZO-2 at putative phosphorylation sites might interfere with ZO-2 interaction with regulatory molecules and other TJ proteins. MET bonds formed at ZO-2 ubiquitination sites likely interfere with ZO-2 degradation and TJ sealing, based on results obtained in cultured epithelial cells transfected with ZO-2 mutated at a MET target lysine residue. Our results shed light on MET male reproductive toxicity and are important to improve regulations regarding the use of OP pesticides and to protect the health of agricultural workers.
Assuntos
Barreira Hematotesticular/efeitos dos fármacos , Inseticidas/farmacologia , Organofosfatos/farmacologia , Compostos Organotiofosforados/farmacologia , Proteína da Zônula de Oclusão-2/metabolismo , Animais , Barreira Hematotesticular/metabolismo , Claudinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Ocludina/metabolismo , Fosfoproteínas/metabolismo , Fosforilação/efeitos dos fármacos , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/metabolismo , Espermatogênese/efeitos dos fármacos , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Proteína da Zônula de Oclusão-1/metabolismoRESUMO
Tribulus terrestris (TT) has been considered as a potential stimulator of testosterone production, which has been related with steroidal saponins prevailing in this plant. Cyclophosphamide (CP) is the most commonly used anticancer and immunosuppressant drug, which causes several toxic effects, especially on the reproductive system. Patients who need to use CP therapy exhibit reduced fertility or infertility, which impacts both physically and emotionally on the decision to use this drug, especially among young men. We hypothesized that the treatment with TT dry extract would protect the male reproductive system against CP toxicity. Mice received dry extract of TT (11 mg/kg) or vehicle by gavage for 14 days. Saline or CP was injected intraperitoneally at a single dose (100 mg/kg) on the 14th day. Animals were euthanized 24 h after CP administration, and testes and epididymis were removed for biochemical and histopathological analysis and sperm evaluation. The dry extract of TT was evaluated by HPLC analysis and demonstrated the presence of protodioscin (1.48%, w/w). CP exposure increased lipid peroxidation, reactive species, and protein carbonylation and altered antioxidant enzymes (SOD, CAT, GPx, GST, and GR). Moreover, acute exposure to CP caused a reduction on 17 ß-HSD activity, which may be related to the reduction in serum testosterone levels, histopathological changes observed in the testes, and the quality of the semen. The present study highlighted the role of TT dry extract to ameliorate the alterations induced by CP administration in mice testes, probably due to the presence of protodioscin.
Assuntos
Ciclofosfamida/efeitos adversos , Substâncias Protetoras/farmacologia , Reprodução/efeitos dos fármacos , Tribulus/química , 17-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Sulfato de Desidroepiandrosterona/metabolismo , Diosgenina/análogos & derivados , Diosgenina/análise , Masculino , Camundongos , Extratos Vegetais/farmacologia , Padrões de Referência , Saponinas/análise , Sêmen/metabolismo , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/patologia , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Testosterona/sangueRESUMO
While many studies have shown that pulp mill effluents can affect ovarian physiology in fish, far fewer studies have considered the effects in males. We conducted a lab study to examine the effects of effluent from a Brazilian pulp and paper mill on hepatic and testicular morphology and various aspects of testicular physiology in the zebrafish Danio rerio. Males were exposed to lab water (control) or 4% effluent for 14â¯days. Effluent exposure did not affect testis size as measured by the gonadosomatic index, but contributed to morphological changes in the seminiferous tubules. The number of cysts with histopathological changes was elevated in effluent-exposed fish and the number of cysts containing spermatids was significantly reduced. The testis of effluent exposed fish had reduced levels of lactate, elevated lactate dehydrogenase activity, increased levels of reactive oxygen species and reduced levels of phosphorylated P38 mitogen-activated protein kinase (pP38 MAPK). Separate studies showed that the addition of lactate to testicular tissue incubated in vitro increased the activation of P38 MAPK. Effluent exposure also increased vacuolization, necrosis, apoptosis, hyperemia, and fat infiltration of the hepatocytes. Collectively, we provide evidence of short term effects of pulp mill effluent on testicular and hepatic physiology and biochemistry in the zebrafish.
Assuntos
Indústrias Extrativas e de Processamento , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Papel , Testículo/efeitos dos fármacos , Águas Residuárias/toxicidade , Madeira , Animais , Apoptose/efeitos dos fármacos , Brasil , Lactato Desidrogenases/metabolismo , Ácido Láctico/metabolismo , Fígado/citologia , Fígado/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Espécies Reativas de Oxigênio/metabolismo , Túbulos Seminíferos/citologia , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/metabolismo , Testículo/citologia , Testículo/metabolismo , Testes de Toxicidade Aguda , Vacúolos/efeitos dos fármacos , Vacúolos/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismoRESUMO
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is considered one of the most toxic dioxins. The effects of TCDD are exerted via binding to the aryl hydrocarbon receptor (AhR). The aim of the present study was to evaluate the possible protective effects of resveratrol, an AhR antagonist, against testicular damage caused by TCDD exposure during pregnancy. Pregnant female Sprague-Dawley rats were divided into four groups: a control group; a group treated with 1µgkg-1, p.o., TCDD on Gestational Day (GD) 15; a group treated with 20µgkg-1, p.o., resveratrol on GD10-21; and a group treated with both TCDD and resveratrol. Rats were weighed and killed, and neonatal testes were collected for histopathological analysis on Postnatal Day (PND) 1. At PND90, adult male rats were killed and the testes collected for histopathological analysis and determination of sperm count. Resveratrol had a protective effect against the effects of TCDD on Sertoli cell number in adult and neonate testes, as well as against the effects of TCDD on abnormal seminiferous tubules in adults. Combined administration of TCDD and resveratrol altered the kinetics of spermatogenesis and the proportion of neonatal testicular compartments compared with the control group In addition, combined TCDD and resveratrol treatment decreased seminiferous tubule diameter in adult male rats compared with the control group. In conclusion, resveratrol may protect against some TCDD-induced testicular damage, but, based on the parameters assessed, the administration of resveratrol and TCDD in combination may result in more severe toxicity than administration of either drug alone.
Assuntos
Poluentes Ambientais/toxicidade , Exposição Materna/efeitos adversos , Dibenzodioxinas Policloradas/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Estilbenos/farmacologia , Testículo/efeitos dos fármacos , Fatores Etários , Animais , Animais Recém-Nascidos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Citoproteção , Feminino , Masculino , Gravidez , Ratos Sprague-Dawley , Receptores de Hidrocarboneto Arílico/efeitos dos fármacos , Receptores de Hidrocarboneto Arílico/metabolismo , Resveratrol , Medição de Risco , Análise do Sêmen , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/metabolismo , Túbulos Seminíferos/patologia , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Células de Sertoli/patologia , Transdução de Sinais/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Estilbenos/toxicidade , Testículo/metabolismo , Testículo/patologiaRESUMO
PURPOSE: To investigate the effect of buserelin on gonadal structure and function in adult male rats. METHODS: Twenty-four adult Wistar male rats were divided into three groups: two treated groups and controls. The first and second treated groups received 300 (low dose) and 500 (high dose) µg/kg buserelin, respectively, and the control group received normal saline. All groups were treated subcutaneously for five days. RESULTS: The seminiferous tubular epithelial thickness was significant decreased in the treated groups compared with those in the control. There was a significant increase in apoptotic cell death in high dose treated group compared with low dose treated and control groups. No significant difference in serum testosterone level was observed after one month in the three groups. CONCLUSION: Buserelin induces apoptotic cell death and decreased diameter and epithelium thickness of seminiferous tubules in the adult rat testes.
Assuntos
Apoptose/efeitos dos fármacos , Busserrelina/administração & dosagem , Fármacos para a Fertilidade Masculina/administração & dosagem , Túbulos Seminíferos/efeitos dos fármacos , Animais , Busserrelina/efeitos adversos , Fármacos para a Fertilidade Masculina/efeitos adversos , Marcação In Situ das Extremidades Cortadas , Masculino , Modelos Animais , Ratos , Ratos Wistar , Túbulos Seminíferos/patologia , Testículo/anatomia & histologia , Testículo/efeitos dos fármacos , Testosterona/sangueRESUMO
Abstract Purpose: To investigate the effect of buserelin on gonadal structure and function in adult male rats. Methods: Twenty-four adult Wistar male rats were divided into three groups: two treated groups and controls. The first and second treated groups received 300 (low dose) and 500 (high dose) µg/kg buserelin, respectively, and the control group received normal saline. All groups were treated subcutaneously for five days. Results: The seminiferous tubular epithelial thickness was significant decreased in the treated groups compared with those in the control. There was a significant increase in apoptotic cell death in high dose treated group compared with low dose treated and control groups. No significant difference in serum testosterone level was observed after one month in the three groups. Conclusion: Buserelin induces apoptotic cell death and decreased diameter and epithelium thickness of seminiferous tubules in the adult rat testes.
Assuntos
Animais , Masculino , Ratos , Túbulos Seminíferos/efeitos dos fármacos , Busserrelina/administração & dosagem , Apoptose/efeitos dos fármacos , Fármacos para a Fertilidade Masculina/administração & dosagem , Túbulos Seminíferos/patologia , Testículo/anatomia & histologia , Testículo/efeitos dos fármacos , Testosterona/sangue , Busserrelina/efeitos adversos , Ratos Wistar , Marcação In Situ das Extremidades Cortadas , Modelos Animais , Fármacos para a Fertilidade Masculina/efeitos adversosRESUMO
Fipronil is an insecticide widely used in agriculture, veterinary medicine and public health that has recently been listed as a potential endocrine disrupter. In the present study we evaluated the effects of perinatal exposure to fipronil during the period of sexual brain differentiation and its later repercussions on reproductive parameters in male rats. Pregnant rats were exposed (via gavage) to fipronil (0.03, 0.3 or 3mgkg-1) from Gestational Day 15 until Postnatal Day 7. Fipronil exposure did not compromise the onset of puberty. In adulthood, there was no effect on organ weight or sperm production. Furthermore, there were no adverse effects on the number of Sertoli cells per seminiferous tubule, testicular and epididymal histomorphometry or histopathology or expression patterns of androgen receptor in the testis. Similarly, no changes were observed in the sexual behaviour or hormone levels. However, in rats exposed to fipronil, changes in sperm motility were observed, with a decrease in motile spermatozoa and an increase in non-mobile spermatozoa, which can compromise sperm quality in these rats. Perinatal exposure to fipronil has long-term effects on sperm parameters, and the epididymis can be a target organ. Additional studies should be undertaken to identify the mechanisms by which fipronil affects sperm motility.
Assuntos
Astenozoospermia/induzido quimicamente , Disruptores Endócrinos/toxicidade , Epididimo/efeitos dos fármacos , Inseticidas/toxicidade , Lactação , Exposição Materna/efeitos adversos , Pirazóis/toxicidade , Administração Oral , Animais , Astenozoospermia/patologia , Forma Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Disruptores Endócrinos/administração & dosagem , Epididimo/patologia , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Inseticidas/administração & dosagem , Masculino , Neurogênese/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Pirazóis/administração & dosagem , Ratos Wistar , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/patologia , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/patologiaRESUMO
The H2-receptor antagonist cimetidine is an antiulcer drug also used for the treatment of cancer due to its antiangiogenic effect. However, this drug has caused structural changes in the seminiferous tubules. Vitamin B12 has been used as a therapeutic agent for the treatment of male infertility. The supplementation of rats with vitamin B12 during cimetidine treatment has recovered the damaged seminiferous tubules, but how this vitamin restores the seminiferous epithelium has not been clarified. In this study, we evaluated whether vitamin B12 improves the number of spermatogonia, spermatocytes, and sperm concentration in cimetidine-treated rats. Adult male rats were treated for 50 days as follows: cimetidine group received 100 mg kg-1 b.w. of cimetidine, cimetidine-B12 group received cimetidine and 3 µg of vitamin B12-hydroxocobalamin, B12 group received only 3 µg of vitamin, and control group received saline. Sperm concentration was calculated and historesin-embedded testes sections were used for the quantitative analyses of spermatogonia (A; In/B) and spermatocytes. TUNEL method and PCNA immunofluorescence were performed. Cimetidine caused a significant reduction in sperm concentration. TUNEL-positive spermatogonia and spermatocytes were correlated to a significant reduction in the number of these cells. In cimetidine-B12 group, sperm concentration was higher than cimetidine group and a significant increase in the number of spermatogonia (stages II-VI) was correlated to a high incidence of PCNA-immunolabeled spermatogonia and spermatocytes. The results show that the supplementation of rats with vitamin B12 during cimetidine treatment increases sperm concentration and exerts a potential effect in the recovery of spermatogonia and spermatocytes.
Assuntos
Cimetidina/farmacologia , Antagonistas dos Receptores H2 da Histamina/farmacologia , Espermatogênese/efeitos dos fármacos , Espermatogônias/efeitos dos fármacos , Vitamina B 12/farmacologia , Vitaminas/farmacologia , Animais , Marcação In Situ das Extremidades Cortadas , Masculino , Ratos , Ratos Sprague-Dawley , Epitélio Seminífero/efeitos dos fármacos , Epitélio Seminífero/ultraestrutura , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/ultraestrutura , Contagem de Espermatozoides , Espermatogônias/ultraestrutura , Espermatozoides/efeitos dos fármacos , Espermatozoides/ultraestruturaRESUMO
This study investigated whether or not prepubertal exposure to the fish contaminants methylmercury (MeHg) and the polychlorinated bisphenol Aroclor in low doses interferes with the histomorphometry of the testes, epididymis, liver and kidneys in rats. Wistar male rats, 21 days old, were allocated into the following: control (n = 17, received corn oil), MeHg (n = 17, received MeHg at 0.5 mg/kg/day), Aroclor (n = 17, received Aroclor at 1.0 mg/kg/day), low mix (n = 18, received MeHg at 0.05 mg/kg/day and Aroclor at 0.1 mg/kg/day), high mix (n = 18, received MeHg at 0.5 mg/kg/day and Aroclor at 1.0 mg/kg/day). Dosing continued from post natal day (PND) 23 to 53, by gavage. Euthanasia was performed on PND 53; or, after an interval of 62 days without exposure to chemicals, on PND 115. The degree of maturation of the seminiferous epithelium was delayed in chemical-exposed groups and testicular interstitial oedema was observed at adulthood. The pattern of male gonad organization was changed in the Aroclor group on PND 53 and in all treated groups at adulthood. The animals from Aroclor, low mix and high mix groups showed a reduction in the number of Sertoli cells. Histological evidence of renal injury was observed in all chemical-exposed groups in both ages. A probable target for MeHg and Aroclor in the reproductive system was Sertoli cells, in which possible dysfunctions could be linked to the other testicular alterations. Curiously, the main deleterious effects were late outcomes, along with the absence of synergistic interaction of MeHg and Aroclor in the parameters investigated. In conclusion, fish pollutants MeHg and Aroclor caused permanent structural damage in male gonads and kidneys after prepubertal exposure, without showing clear chemical interactions.