RESUMEN
Pre- and/or post-natal administrations of di(2-ethylhexyl) phthalate (DEHP) in experimental animals cause alterations in the spermatogenesis. However, the mechanism by which DEHP affects fertility is unknown and could be through alterations in the survival and differentiation of the gonocytes. The aim of the present study was to evaluate the effect of a single administration of DEHP in newborn mice on gonocytic proliferation, differentiation and survival and its long-term effects on seminiferous epithelium and sperm quality. BALB/c mice distributed into Control and DEHP groups were used. Each animal in the DEHP group was given a single dose of 500 mg/Kg at birth. The animals were analyzed at 1, 2, 4, 6, 8, 10 and 70 days postpartum (dpp). Testicular tissues were processed for morphological analysis to determine the different types of gonocytes, differentiation index, seminiferous epithelial alterations, and immunoreactivity to Stra8, Pcna and Vimentin proteins. Long-term evaluation of the seminiferous epithelium and sperm quality were carried out at 70 dpp. The DEHP animal group presented gonocytic degeneration with delayed differentiation, causing a reduction in the population of spermatogonia (Stra8 +) in the cellular proliferation (Pcna+) and disorganization of Vimentin filaments. These events had long-term repercussions on the quality of the seminiferous epithelium and semen. Our study demonstrates that at birth, there is a period that the testes are extremely sensitive to DEHP exposure, which leads to gonocytic degeneration and delay in their differentiation. This situation can have long-term repercussions or permanent effects on the quality of the seminiferous epithelium and sperm parameters.
Asunto(s)
Animales Recién Nacidos , Dietilhexil Ftalato , Ratones Endogámicos BALB C , Animales , Dietilhexil Ftalato/toxicidad , Masculino , Ratones , Testículo/efectos de los fármacos , Testículo/crecimiento & desarrollo , Espermatogénesis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Plastificantes/toxicidad , Femenino , Epitelio Seminífero/efectos de los fármacosRESUMEN
BACKGROUND: Venlafaxine (selective serotonin and norepinephrine reuptake inhibitor) use has increased worldwide. However, the impact of venlafaxine on testes and sperm parameters has not been investigated. OBJECTIVES: We evaluated venlafaxine impact on testicular and sperm parameters and verified whether the changes are reversible. METHODS: Animals from venlafaxine-35 days and venlafaxine-65 days groups received 30 mg/kg of venlafaxine for 35 days. Control-35 days and control-65 days received distilled water. In control-65 days and venlafaxine-65 days, the treatment was interrupted for 30 days. Sperm concentration, morphology, motility, and mitochondrial activity were analyzed. Number of step 19 spermatids (NLS), frequency of tubules with spermiation failure, Sertoli cells number, and TUNEL-positive germ cells were quantified. Testicular aromatase, connexin 43 (Cx43) immunoexpression, Cx43 protein levels, and Cx43 expression were evaluated. Either intratesticular testosterone or estrogen levels were measured. RESULTS: Venlafaxine impaired sperm morphology, reduced sperm concentration, mitochondrial activity, and sperm motility. The frequency of tubules with spermiation failure and NLS increased in parallel to increased Cx43 immunoexpression; mRNA and protein levels; and aromatase, testosterone, and estrogen levels. An increase in germ cell death and decreased Sertoli cells number were observed. In venlafaxine-65 days, except for sperm motility, mitochondrial activity, Sertoli cells number, and germ cell death, all other parameters were partially or totally recovered. CONCLUSION: Venlafaxine increases testosterone aromatization and Cx43. This drug, via high estrogen levels, disturbs Sertoli cells, induces germ cell death, and impairs spermiation and sperm parameters. The restoration of spermiation associated with the decreased Cx43 and hormonal levels in venlafaxine-65 days reinforces that high estrogen levels are related to venlafaxine-induced changes. The presence of damaged Sertoli cells, germ cell death, and low sperm motility in venlafaxine-65 days indicates that interruption of treatment for 30 days was insufficient for testicular recovery and points to a long-term estrogen impact on the seminiferous epithelium.
Asunto(s)
Estrógenos/metabolismo , Epitelio Seminífero/efectos de los fármacos , Inhibidores de Captación de Serotonina y Norepinefrina/efectos adversos , Espermatozoides/efectos de los fármacos , Clorhidrato de Venlafaxina/efectos adversos , Animales , Aromatasa/metabolismo , Conexina 43/metabolismo , Evaluación Preclínica de Medicamentos , Masculino , Ratas Sprague-Dawley , Epitelio Seminífero/enzimología , Motilidad Espermática/efectos de los fármacos , Testosterona/metabolismoRESUMEN
SUMMARY: The study reported the influence of the high and acute dose of Letrozole on the testis morphology in paca (Cuniculus paca), an aromatase inhibitor that reduces the endogenous estrogen, the essential hormone for spermatogenesis. Morphological changes were observed in seminiferous epithelium with germ cells with apoptotic characteristics and presence of vacuoles and nuclei in pycnose.
RESUMEN: El objetivo de este estudio fue analizar la influencia de una dosis alta de Letrozol en la morfología de los testículos de la paca (Cuniculus paca), un inhibidor de la aromatasa que reduce el estrógeno endógeno, la hormona esencial para la espermatogénesis. Se observaron cambios morfológicos en el epitelio seminífero con células germinales con características apoptóticas y la presencia de vacuolas y núcleos en picnosis.
Asunto(s)
Animales , Masculino , Testículo/efectos de los fármacos , Inhibidores de la Aromatasa/administración & dosificación , Cuniculidae , Letrozol/administración & dosificación , Epitelio Seminífero/efectos de los fármacos , Espermatogénesis/efectos de los fármacos , Inmunohistoquímica , Orquiectomía , Microscopía Electrónica de Transmisión , Células Germinativas/efectos de los fármacosRESUMEN
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.
Asunto(s)
Amaranthaceae/química , Extractos Vegetales/farmacología , Epitelio Seminífero/efectos de los fármacos , Espermatogénesis/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Células Germinativas/efectos de los fármacos , Células Germinativas/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Raíces de Plantas/química , Epitelio Seminífero/patología , Túbulos Seminíferos/efectos de los fármacos , Túbulos Seminíferos/patología , Células de Sertoli/efectos de los fármacos , Células de Sertoli/patologíaRESUMEN
The aim of this study was to investigate carnitine action against negative effects of etoposide on stem/progenitor spermatogonia and on sperm production. Carnitine (250 mg/kg body weight/day) and etoposide (5 mg/kg body weight/day) were administered from 25-days postpartum to 32-days postpartum. Testes were collected at 32-days postpartum, 64-days postpartum, and 127-days postpartum, and submitted to the immuno-labeling of UTF1, SOX2, and PLZF proteins to identify undifferentiated spermatogonia populations. At 127-days postpartum, sperm were collected for analysis. Carnitine+etoposide group showed a higher numerical density of spermatogonia labeled for all studied proteins at 64-days postpartum (critical age) compared to the etoposide group. Moreover, there was an improvement of spermatic parameters and sperm DNA integrity in rats of the carnitine+etoposide group in comparison with rats of the etoposide group. The results suggest that carnitine improves the self-renewal of undifferentiated spermatogonia and promotes a partial protection on them, alleviating the etoposide harmful late effects and leading to an enhancement of the sperm parameters in adulthood.
Asunto(s)
Carnitina/farmacología , Autorrenovación de las Células/efectos de los fármacos , Etopósido/toxicidad , Espermatogonias/citología , Espermatogonias/efectos de los fármacos , Animales , Daño del ADN , Relación Dosis-Respuesta a Droga , Masculino , Tamaño de los Órganos/efectos de los fármacos , Proteína de la Leucemia Promielocítica con Dedos de Zinc/metabolismo , Ratas , Factores de Transcripción SOXB1/metabolismo , Epitelio Seminífero/efectos de los fármacos , Epitelio Seminífero/crecimiento & desarrollo , Espermatogénesis/efectos de los fármacos , Espermatogonias/metabolismo , Testículo/efectos de los fármacos , Testículo/crecimiento & desarrollo , Factores de Transcripción/metabolismoRESUMEN
One of the most consumed pesticides in the world is glyphosate, the active ingredient in the herbicide ROUNDUP®. Studies demonstrate that glyphosate can act as an endocrine disruptor and that exposure to this substance at critical periods in the developmental period may program the fetus to induce reproductive damage in adulthood. Our hypothesis is that maternal exposure to glyphosate during pregnancy and lactation in mice will affect the development of male reproductive organs, impairing male fertility during adult life. Female mice consumed 0.5% glyphosate-ROUNDUP® in their drinking water [glyphosate-based herbicide (GBH) group] or filtered water [control (CTRL) group] from the fourth day of pregnancy until the end of the lactation period. Male F1 offspring were designated, according to their mother's treatment, as CTRL-F1 and GBH-F1. Female mice that drank glyphosate displayed reduced body weight (BW) gain during gestation, but no alterations in litter size. Although GBH male F1 offspring did not exhibit modifications in BW, they demonstrated delayed testicular descent. Furthermore, at PND150, GBH-F1 mice presented a lower number of spermatozoa in the cauda epididymis and reduced epithelial height of the seminiferous epithelium. Notably, intratesticular testosterone concentrations were enhanced in GBH-F1 mice; we show that it is an effect associated with increased plasma and pituitary concentrations of luteinizing hormone. Therefore, data indicate that maternal exposure to glyphosate-ROUNDUP® during pregnancy and lactation may lead to decreased spermatogenesis and disruptions in hypothalamus-pituitary-testicular axis regulation in F1 offspring.
Asunto(s)
Glicina/análogos & derivados , Herbicidas/toxicidad , Exposición Materna/efectos adversos , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Espermatogénesis/efectos de los fármacos , Animales , Animales Lactantes , Modelos Animales de Enfermedad , Femenino , Ganancia de Peso Gestacional/efectos de los fármacos , Glicina/toxicidad , Humanos , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/metabolismo , Lactancia , Hormona Luteinizante/sangre , Hormona Luteinizante/metabolismo , Masculino , Ratones , Embarazo , Efectos Tardíos de la Exposición Prenatal/sangre , Efectos Tardíos de la Exposición Prenatal/patología , Epitelio Seminífero/efectos de los fármacos , Epitelio Seminífero/patología , Recuento de Espermatozoides , Espermatozoides/efectos de los fármacos , Espermatozoides/crecimiento & desarrollo , Testosterona/análisis , Testosterona/metabolismo , GlifosatoRESUMEN
The aim of this study was to describe the seminal, histomorphological and hormonal effects of the oral indenopyridine RTI-4587-073(l) on feline testicle. Clinical side effects were also recorded. Sixty testicles of 30 adult cats that had been treated (d 0) with RTI-4587-073(l) 12.5 mg/kg PO and randomly hemiorchiectomized twice on: day -14 (n = 8), 6 h (n = 6), 12 h (n = 8), 24 h (n = 6), day 7 (n = 8), day 14 (n = 6), day 21 (n = 6), day 35 (n = 6) or day 42 (n = 6) were studied. Before each hemiorchiectomy, fecal samples for testosterone (T) measurement were collected and the testes were grossly and ultrasound examined. This indenopyridine did not cause changes in testicular weight (P > 0.1), volume (P > 0.1), echostructure, gonadosomatic index (P > 0.1), fecal T concentrations (P > 0.1), nor clinical side effects. A severe disorganization of the cytoarchitecture of the seminiferous epithelium, sloughed cells and fluid, were observed in the 6 h samples up to a maximum at 24 h. Tubular diameter (P < 0.01) increased twice, during the first 24 h and on d 35. Germinal epithelium achieved its minimum height on d 14 to rapidly recover thereafter. This treatment caused a significant decrease in the volume of all the seminiferous cell components, except spermatogonias. All histotological parameters normalized by the end of the study. It was concluded that RTI-4587-073(l) severely disrupted spermatogenesis during the first 24 h after treatment returning to normality in approximately one spermatic cycle without clinical side effects.
Asunto(s)
Gatos , Anticonceptivos Masculinos/farmacología , Indenos/farmacología , Orquiectomía/veterinaria , Piperidinas/farmacología , Testículo/efectos de los fármacos , Animales , Masculino , Orquiectomía/métodos , Distribución Aleatoria , Epitelio Seminífero/efectos de los fármacos , Recuento de EspermatozoidesRESUMEN
This study evaluated the effects of diet containing taro flour on hormone levels and the seminiferous tubules morphology of rats. After weaning, the male rats were divided into two groups (n=12 each): control group (CG) treated with control diet and taro group (TG), fed with 25% taro flour for 90 days. Food, caloric intake, mass and body length were evaluated at experiment end. Testis followed the standard histological processing. Immunostaining was performed using an anti-vimentin antibody to identify Sertoli cells. In histomorphometry, total diameter, total area, epithelial height, luminal height and luminal area were analyzed. The testosterone levels were performed using the radioimmunoassay method. Group TG presented (P<0.05): increase in mass, body length, testicular weight, histomorphometric parameters and hormonal levels. Food intake, calorie and Sertoli cells not presented statistical differences. The taro promoted increase in the testicles parameters and hormones.
Asunto(s)
Colocasia/química , Harina , Epitelio Seminífero/citología , Epitelio Seminífero/metabolismo , Células de Sertoli/metabolismo , Testosterona/metabolismo , Animales , Masculino , Ratas , Ratas Wistar , Epitelio Seminífero/efectos de los fármacos , Células de Sertoli/citología , Células de Sertoli/efectos de los fármacosRESUMEN
The acute promyelocytic leukemia (APL) is a rare disease, affecting 0.1/100,000 individuals globally. Despite significant advances in APL therapy, some patients still experience relapsed disease. Currently, arsenic trioxide (As2O3) was found to be effective in relapsed APL treatment and considered as standard treatment for these cases. However, it has been shown that exposure to As2O3 may exert adverse effects on the male reproductive system since this substance might also induce apoptosis of other important cell types including stem cells. Studies demonstrated that treatment with this metallic substance decreased plasma levels of testosterone and interfered with sperm parameters such as concentration, motility, and viability. In addition, As2O3 was found to produce significant damage to spermatocytes, which may be associated with testicular toxicity and consequent inhibition of spermatogenesis. The aim of this study was to determine sub-chronic treatment effects of As2O3 on sperm and testicular morphology, androgen receptor (AR) immunoreactivity in testes and epididymis, in addition to evaluation of fertility parameters in adult male mice. Thirty adult Swiss mice were divided into three experimental groups: control; received distilled water (vehicle) while treated received 0.3 or 3 mg/kg/day As2O3 subcutaneously, for 5 days per week, followed by 2 days of interruption, for 5 weeks. Results showed that As2O3 (1) decreased spermatozoa number, (2) produced seminiferous epithelium degeneration and exfoliation of germ cells tubule lumen (3) altered nucleus/cytoplasm proportion of Leydig cells and (4) reduced AR immunoreactivity in both Leydig and epithelial epididymal cells. Further, fetal viability tests demonstrated an increase in post-implantation loss in females that were mated with As2O3-treated males. Data indicate that As2O3 exposure altered the spermatogenic process and subsequently fetal viability.
Asunto(s)
Viabilidad Fetal/efectos de los fármacos , Óxidos/toxicidad , Testículo/efectos de los fármacos , Animales , Trióxido de Arsénico , Arsenicales/administración & dosificación , Modelos Animales de Enfermedad , Epidídimo/efectos de los fármacos , Epidídimo/metabolismo , Fertilidad/efectos de los fármacos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Células Intersticiales del Testículo/efectos de los fármacos , Células Intersticiales del Testículo/metabolismo , Masculino , Ratones , Óxidos/administración & dosificación , Receptores Androgénicos/metabolismo , Reproducción/efectos de los fármacos , Epitelio Seminífero/efectos de los fármacos , Epitelio Seminífero/metabolismo , Espermatogénesis/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Espermatozoides/metabolismo , Testículo/metabolismo , Pruebas de Toxicidad Subcrónica , Aumento de Peso/efectos de los fármacosRESUMEN
The Sertoli cell plays a vital role during the spermatogenesis process and has been identified as one of the main targets of the toxic action of heavy metals on the seminiferous epithelium. In the present work, the effect of lead (Pb), Arsenic (As), and Cadmium (Cd) in primary cultures of Sertoli cells was analyzed by measuring the expression of the genes Cldn11, Ocln, and Gja1 that participate in the tight and gap junctions, which are responsible for maintaining the blood-testis barrier. Sertoli cells were isolated from the testes of Wistar rats. Sertoli cell cultures were exposed separately and at the same concentrations of three heavy metals for 48 h. Subsequently, gene expression was measured by real-time polymerase chain reaction. In the morphological analysis of the cultures, after 24 h, the cultures exposed to Cd showed greatest detachment of the monolayer, followed by those exposed to As and Pb. As for gene expression patterns, As induced a decrease in the expression of the Cldn11 gene at 24 and 48 h (p < 0.01) and in that of Ocln at 24 (p < 0.001) and 48 h (p < 0.01), whereas Cd induced overexpression of the Gja1 gene from day 1 of exposure (p < 0.001) and subexpression of the Ocln gene (p < 0.05) at 24 h. Because each of these three metals generated different expression patterns in the three genes, we can postulate that the mechanisms of damage that they induce are different; therefore, the effect that they exert on the Sertoli cell occurs through different pathways, generating changes in structural proteins, altering Sertoli cell morphology, and compromising its function in the regulation of the spermatogenesis process.
Asunto(s)
Arsénico/farmacología , Barrera Hematotesticular/efectos de los fármacos , Cadmio/farmacología , Plomo/farmacología , Células de Sertoli/efectos de los fármacos , Testículo/efectos de los fármacos , Animales , Uniones Comunicantes/efectos de los fármacos , Uniones Comunicantes/metabolismo , Masculino , Proteínas de la Membrana/genética , Ratas Wistar , Epitelio Seminífero/efectos de los fármacos , Células de Sertoli/citología , Espermatogénesis/efectos de los fármacos , Testículo/citología , Testículo/metabolismoRESUMEN
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.
Asunto(s)
Cimetidina/farmacología , Antagonistas de los Receptores H2 de la Histamina/farmacología , Espermatogénesis/efectos de los fármacos , Espermatogonias/efectos de los fármacos , Vitamina B 12/farmacología , Vitaminas/farmacología , Animales , Etiquetado Corte-Fin in Situ , Masculino , Ratas , Ratas Sprague-Dawley , Epitelio Seminífero/efectos de los fármacos , Epitelio Seminífero/ultraestructura , Túbulos Seminíferos/efectos de los fármacos , Túbulos Seminíferos/ultraestructura , Recuento de Espermatozoides , Espermatogonias/ultraestructura , Espermatozoides/efectos de los fármacos , Espermatozoides/ultraestructuraRESUMEN
Several different strategies have been adopted in attempt to recover from chemotherapy-damaged spermatogenesis that is often seen in oncologic patients. In this study, we have evaluated the impact of short period of exposure to busulphan on the haemogram and seminiferous epithelium of adult rats, focusing on spermatogonial depletion and Sertoli cell (SC) integrity. We then examined whether vitamin B12 supplementation improves the haematological parameters and spermatogonia number. The animals received 10 mg/kg of busulphan (BuG) or busulfan+vitamin B12 (Bu/B12 G) on the first and fourth days of treatment. In H.E.-stained testicular sections, the areas of the seminiferous tubule (ST) and seminiferous epithelium were measured. The number of spermatogonia in H.E-stained and PCNA-immunolabelled testicular sections was quantified. The frequency of tubules with abnormal SC nuclei or TUNEL-positive SC was evaluated. Vimentin immunofluorescence in ST was also evaluated. In BuG and Bu/B12 G, the animals showed leukopenia and thrombocytopenia, but the body weight reduced only in BuG. The areas of ST and seminiferous epithelium decreased in Bu/B12 G and BuG. In BuG, the number of H.E.-stained and PCNA-immunolabelled spermatogonia reduced significantly. The frequency of tubules containing abnormal SC nuclei and TUNEL-positive SC increased and the vimentin immunoexpression pattern changed. In Bu/B12 G, the number of H.E.-stained or PCNA-immunolabelled spermatogonia increased fourfold in comparison with BuG. The structural changes in ST after 6 days of busulphan exposure may be associated with the potential effect of this anti-neoplastic agent on SC. The increased number of spermatogonia in the busulphan-treated animals receiving vitamin B12 indicates that this vitamin can be an adjuvant therapy to improve the fertility in male cancer patients.
Asunto(s)
Células Madre Germinales Adultas/efectos de los fármacos , Antineoplásicos Alquilantes/toxicidad , Busulfano/toxicidad , Epitelio Seminífero/efectos de los fármacos , Vitamina B 12/farmacología , Células Madre Germinales Adultas/patología , Animales , Peso Corporal/efectos de los fármacos , Leucopenia/inducido químicamente , Leucopenia/prevención & control , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas Sprague-Dawley , Epitelio Seminífero/patología , Células de Sertoli/efectos de los fármacos , Células de Sertoli/patología , Espermatogénesis/efectos de los fármacos , Testículo/efectos de los fármacos , Testículo/metabolismo , Testículo/patología , Trombocitopenia/inducido químicamente , Trombocitopenia/prevención & control , Vimentina/metabolismoRESUMEN
Pyrimethamine (PYR) is a drug used in the treatment of newborn with congenital Toxoplasmosis. Even when PYR is highly specific against parasites, it may provoke neutropenia in the patients apart from other affectations, conditions that usually justify its suspension. Moreover, medication against congenital toxoplasmosis coincides with the proliferation stage of Sertoli and germ cells. Although, there are several reports on the effect of this drug on mature testes, records of its effects on the testes of young individuals yet in the process of growth are still lacking. This work was aimed to study the effects of in vivo administration of PYR in the first 21 days of life of male rat pups by evaluating their testicular alterations and its long-term sequels on fertility. Through the determination of the levels of seminiferous epithelium maturity, apoptotic index and cell proliferation index at 7, 14, 35 and 90 days post-natal using immunocytochemical studies. The fertility of the treated rats was evaluated at 90 days. PYR-treated animals were found to undergo some kind of delays in seminiferous epithelium maturity, decreased cell proliferation index and an increase in apoptosis when compared with the control (p < 0.05). Epididymal sperm counts were also affected (p < 0.05). The application of folic acid (FA) in newborns treated with PYR decreased the severity of the problem (p < 0.05). This study provides strong evidence that the effect of PYR on testicular development is specific. It reinforces the importance of FA application in neonates treated with PYR to prevent the effect of the later on spermatogenesis.
Asunto(s)
Fertilidad/efectos de los fármacos , Antagonistas del Ácido Fólico/efectos adversos , Pirimetamina/efectos adversos , Epitelio Seminífero/efectos de los fármacos , Testículo/patología , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ácido Fólico/farmacología , Antagonistas del Ácido Fólico/farmacología , Masculino , Pirimetamina/farmacología , Ratas , Ratas Wistar , Células de Sertoli/efectos de los fármacos , Espermatogénesis/efectos de los fármacos , Testículo/citología , Toxoplasmosis/tratamiento farmacológicoRESUMEN
The incidence of male reproductive pathologies, such as hypospadias, cryptorchidism, testicular cancer, and low sperm production in adulthood, is increasing and may be related to exposure to environmental contaminants. The silver nanoparticles (AgNP) are a new class of chemical compounds commonly used in both medical and nonmedical settings, and they affect development of spermatogonial stem cells in vitro. The aim of this study was to examine the adverse productive toxic effects of AgNPs in male Wistar rats exposed during the prepubertal period and sacrificed at postnatal day (PND) 53 and PND90. Growth was assessed by daily weighing. The progress of puberty in the rats was measured by preputial separation, while spermatogenesis was assayed by (1) measuring the sperm count in testes and epididymis and (2) examining the morphology and morphometry of seminiferous epithelium using stereological analysis. In addition, testosterone and estradiol levels were assayed by radioimmunoassay. The weight of the animals at PND90 did not change markedly, but growth was less in the group treated with AgNP at 50 µg/kg from PND34 to PND53. AgNP exposure produced a delay in puberty in both treated groups. Decreased sperm reserves in the epididymis and diminished sperm transit time were observed at PND53, while a reduction in sperm production occurred at PND90. The morphology of the seminiferous epithelium was markedly altered. Data demonstrated that prepubertal exposure to AgNP altered reproductive development in prepubertal male Wistar rats, as evidenced by impairment in spermatogenesis and a lower sperm count in adulthood.
Asunto(s)
Enfermedades de los Genitales Masculinos/inducido químicamente , Nanopartículas del Metal/efectos adversos , Animales , Peso Corporal/efectos de los fármacos , Epidídimo/efectos de los fármacos , Estradiol/sangre , Masculino , Pubertad/efectos de los fármacos , Ratas , Ratas Wistar , Epitelio Seminífero/efectos de los fármacos , Recuento de Espermatozoides , Espermatogénesis/efectos de los fármacos , Testículo/efectos de los fármacos , Testosterona/sangreRESUMEN
Sexual differentiation in the brain takes place from late gestation to the early postnatal days. This is dependent on the conversion of circulating testosterone into estradiol by the enzyme aromatase. The glyphosate was shown to alter aromatase activity and decrease serum testosterone concentrations. Thus, the aim of this study was to investigate the effect of gestational maternal glyphosate exposure (50 mg/kg, NOAEL for reproductive toxicity) on the reproductive development of male offspring. Sixty-day-old male rat offspring were evaluated for sexual behavior and partner preference; serum testosterone concentrations, estradiol, FSH and LH; the mRNA and protein content of LH and FSH; sperm production and the morphology of the seminiferous epithelium; and the weight of the testes, epididymis and seminal vesicles. The growth, the weight and age at puberty of the animals were also recorded to evaluate the effect of the treatment. The most important findings were increases in sexual partner preference scores and the latency time to the first mount; testosterone and estradiol serum concentrations; the mRNA expression and protein content in the pituitary gland and the serum concentration of LH; sperm production and reserves; and the height of the germinal epithelium of seminiferous tubules. We also observed an early onset of puberty but no effect on the body growth in these animals. These results suggest that maternal exposure to glyphosate disturbed the masculinization process and promoted behavioral changes and histological and endocrine problems in reproductive parameters. These changes associated with the hypersecretion of androgens increased gonadal activity and sperm production.
Asunto(s)
Glicina/análogos & derivados , Gonadotropinas Hipofisarias/metabolismo , Herbicidas/toxicidad , Exposición Materna/efectos adversos , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Reproducción/efectos de los fármacos , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Estradiol/sangre , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Glicina/toxicidad , Hormona Luteinizante/sangre , Masculino , Preferencia en el Apareamiento Animal/efectos de los fármacos , Preferencia en el Apareamiento Animal/fisiología , Hipófisis/efectos de los fármacos , Hipófisis/metabolismo , Embarazo , Efectos Tardíos de la Exposición Prenatal/sangre , ARN Mensajero/metabolismo , Ratas , Reproducción/fisiología , Epitelio Seminífero/efectos de los fármacos , Epitelio Seminífero/patología , Maduración Sexual/efectos de los fármacos , Espermatogénesis/efectos de los fármacos , Testosterona/sangre , GlifosatoRESUMEN
Treatment of gastric ulcer with cimetidine reduces acid secretion and interferes in the vitamin B(12) absorption. Regarding the harmful effect of cimetidine on the seminiferous tubules, the aim of the present study was to verify if prolonged treatment with cimetidine causes vitamin B(12) deficiency and whether the testicular damages are attenuated by vitamin B(12) supplementation. Adult male rats received, for 50 days, cimetidine (CMTG), cimetidine and vitamin B(12) (CMT/B(12)G), vitamin B(12) (B(12)G) and saline solution (CG). Vitamin B(12) and homocysteine plasma levels were evaluated and the testes were embedded in glycol methacrylate for the morphometric analyses of total, epithelial and luminal areas of the seminiferous tubules, number of Sertoli cells and frequencies of tubules according to stages and containing Sertoli and germ cells in the lumen. Terminal deoxynucleotidyl-transferase mediated dUTP nick end labeling (TUNEL) method and proliferating cell nuclear antigen (PCNA) immunohistochemistry were carried out. CMTG showed TUNEL-positive Sertoli cells and significant reductions in the epithelial and total tubular areas, number of Sertoli cells and frequency of tubules VII-VIII. In the CMT/B(12)G, the number of Sertoli cells and the epithelial and total tubular areas were similar to CG. The number of Sertoli cells (in B(12)G) and the frequency of tubules at stages VII-VIII (in B(12)G and CMT/B(12)G) increased significantly; PCNA-positive Sertoli cells were found in these groups. Although cimetidine was not able to induce vitamin B(12) deficiency, this drug causes tubular atrophy due to Sertoli cell damage and loss of germ cells. However, vitamin B(12) supplement is able to stimulate spermatogenesis and restore the number of Sertoli cells, softening the harmful effect of cimetidine on spermatogenesis.
Asunto(s)
Cimetidina/farmacología , Antagonistas de los Receptores H2 de la Histamina/farmacología , Epitelio Seminífero/efectos de los fármacos , Vitamina B 12/farmacología , Animales , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Masculino , Ratas , Epitelio Seminífero/metabolismoRESUMEN
BACKGROUND: Amifostine is an efficient cytoprotector against toxicity caused by some chemotherapeutic drugs. Doxorubicin, a potent anticancer anthracycline, is known to produce spermatogenic damage even in low doses. Although some studies have suggested that amifostine does not confer protection to doxorubicin-induced testicular damage, schedules and age of treatment have different approach depending on the protocol. Thus, we proposed to investigate the potential cytoprotective action of amifostine against the damage provoked by doxorubicin to prepubertal rat testes (30-day-old) by assessing some macro and microscopic morphometric parameters 15, 30 and 60 days after the treatment; for fertility evaluation, quantitative analyses of sperm parameters and reproductive competence in the adult phase were also carried out. METHODS: Thirty-day-old male rats were distributed into four groups: Doxorubicin (5 mg/kg), Amifostine (400 mg/kg), Amifostine/Doxorubicin (amifostine 15 minutes before doxorubicin) and Sham Control (0.9% saline solution). "Standard One Way Anova" parametric and "Anova on Ranks" non-parametric tests were applied according to the behavior of the obtained data; significant differences were considered when p < 0.05. RESULTS: The rats killed 30 and 60 days after doxorubicin treatment showed diminution of seminiferous epithelium height and reduction on the frequency of tubular sections containing at least one type of differentiated spermatogonia; reduction of sperm concentration and motility and an increase of sperm anomalous forms where observed in doxorubicin-treated animals. All these parameters were improved in the Amifostine/Doxorubicin group only when compared to Doxorubicin group. Such reduction, however, still remained below the values obtained from the Sham Control group. Nevertheless, the reproductive competence of doxorubicin-treated rats was not improved by amifostine pre-administration. CONCLUSIONS: These results suggest that amifostine promotes a significant reduction of the doxorubicin long-term side effects on the seminiferous epithelium of prepubertal rats, which is reflected in the epidydimal fluid parameters in the adult phase. However, fertility status results suggest that such protection may not be effective against sperm DNA content damage. Further investigation of sperm DNA integrity must be carried out using amifostine and doxorubicin-treated experimental models.
Asunto(s)
Amifostina/farmacología , Doxorrubicina/efectos adversos , Fertilidad/efectos de los fármacos , Epitelio Seminífero/efectos de los fármacos , Enfermedades Testiculares/inducido químicamente , Enfermedades Testiculares/prevención & control , Animales , Antibióticos Antineoplásicos/efectos adversos , Citoprotección/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Femenino , Fertilidad/fisiología , Estado de Salud , Masculino , Embarazo , Protectores contra Radiación/farmacología , Ratas , Ratas Wistar , Análisis de Semen , Epitelio Seminífero/patología , Maduración Sexual/efectos de los fármacos , Enfermedades Testiculares/patologíaRESUMEN
Organophosphates like O,O-diethyl O-2-isopropyl-6-methyl pyrimidinyl-4-g-1-phosphorothioate (diazinon) are pesticides used worldwide, which can affect both animals and man even after a single exposure. Whereas their toxicity is due to acetylcholinesterase inhibition, their secondary toxic effects have been related to free oxygen radicals. This study evaluates the effects of a single dose of diazinon and melatonin-a powerful antioxidant-on plasmatic acetylcholinesterase activity and testis histopathology in adult mice 1 and 32 days post-treatment. Diazinon diminished the plasma acetylcholinesterase activity on day 1 post-treatment, although testosterone levels remained unaffected. Morphometrical analysis showed a decrease in seminiferous epithelium height (days 1 and 32), whereas an increase in testicular superoxide dismutase (SOD) activity was detected (day 32). Melatonin pretreatment prevented every alteration induced by diazinon, except the diminution of acetylcholinesterase plasmatic activity. Testicular damage might be due to elevated concentrations of free oxygen radicals released upon diazinon exposure, inducing alterations in the DNA and promoting local apoptosis; however, antioxidant pretreatment with melatonin prevents or diminishes this damage.
Asunto(s)
Antioxidantes/farmacología , Inhibidores de la Colinesterasa/toxicidad , Diazinón/toxicidad , Insecticidas/toxicidad , Melatonina/farmacología , Enfermedades Testiculares/prevención & control , Testículo/efectos de los fármacos , Acetilcolinesterasa/sangre , Animales , Colinesterasas/sangre , Colinesterasas/efectos de los fármacos , Antagonismo de Drogas , Masculino , Ratones , Estrés Oxidativo/efectos de los fármacos , Epitelio Seminífero/efectos de los fármacos , Epitelio Seminífero/patología , Superóxido Dismutasa/metabolismo , Enfermedades Testiculares/inducido químicamente , Enfermedades Testiculares/metabolismo , Enfermedades Testiculares/patología , Testículo/enzimología , Testículo/patología , Testosterona/sangreRESUMEN
Chronic exposure to ethanol may results in pathophysiologic changes in cellular function. The present work was designed to investigate the morphology of testis submitted to experimental ethanol ingestion. Experimental animals were divided into two groups. The control group (n=23) received a solid diet and tap water and the alcoholic group (n=23) received the same solid diet and ethanol P.A. diluted 20% in water (v/v). After 120 days of treatment, all animals were anesthetized, weighed and sacrificed. Testosterone and luteinizing hormone levels in serum were lower in the alcoholic group than in the control group. Histological and ultrastructural alterations were observed in the testicular alcoholic germinative cells like enormous spaces, lipid droplets accumulation, digestive vacuoles, irregular diameter of the seminiferous tubules and interstitial dilated blood vessels. It was concluded that 20% ethanol provokes lesions on the testis germinative epithelium probably inducing gonadal dysfunction.
Asunto(s)
Etanol/toxicidad , Infertilidad Masculina/inducido químicamente , Espermatogonias/efectos de los fármacos , Espermatogonias/patología , Testículo/efectos de los fármacos , Testículo/patología , Alcoholismo/metabolismo , Alcoholismo/patología , Alcoholismo/fisiopatología , Animales , Depresores del Sistema Nervioso Central/toxicidad , Vesículas Citoplasmáticas/efectos de los fármacos , Vesículas Citoplasmáticas/metabolismo , Vesículas Citoplasmáticas/patología , Modelos Animales de Enfermedad , Infertilidad Masculina/patología , Infertilidad Masculina/fisiopatología , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/fisiología , Hormona Luteinizante/análisis , Hormona Luteinizante/sangre , Masculino , Epitelio Seminífero/efectos de los fármacos , Epitelio Seminífero/metabolismo , Epitelio Seminífero/patología , Sigmodontinae/anatomía & histología , Sigmodontinae/metabolismo , Espermatogonias/metabolismo , Enfermedades Testiculares/inducido químicamente , Enfermedades Testiculares/metabolismo , Enfermedades Testiculares/patología , Testículo/metabolismo , Testosterona/análisis , Testosterona/sangreRESUMEN
Cisplatin is a potent drug used in clinical oncology but causes spermatogenesis damage. Amifostine is a drug used against toxicity caused by ionizing irradiation and chemotherapeutic drugs. Since cisplatin provokes fertility and induces germ cell apoptosis and necrosis, we proposed to evaluate the amifostine cytoprotective action on testes of cisplatin-treated rats. Thirty-day-old prepubertal Wistar rats received a single cisplatin dose of 5 mg/kg and were killed after 3, 6, and 12 hr. The hematoxylin-eosin stained testicular sections were submitted to histological, morphometric, and stereological analysis. The terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labeling (TUNEL) method was used to label apoptotic cells. TUNEL-positive and TUNEL-negative germ cells with abnormal nuclear morphology (ANM) were scored. Significant alterations of greater part of the parameters occurred in the cisplatin-treated group (CE) compared to the group that received amifostine before the cisplatin-treatment (ACE); however, testicular weight and volume did not vary between these groups. Tubular diameter was reduced in CE in comparison to ACE rats, while interstitial tissue and lymphatic space volume and volume density were significantly higher in CE rats; interstitial testicular edema probably occurred in cisplatin-treated rats. CE rats showed important histological alterations, which were more accentuated than in ACE rats. The numerical densities of apoptotic germ cells and TUNEL-negative cells with ANM were lower in ACE than in CE rats. In conclusion, the amifostine previously administered to prepubertal rats reduced the testicular damage caused by cisplatin. We conclude that amifostine partially protected the rat seminiferous epithelium against cisplatin toxicity.