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1.
Ecotoxicol Environ Saf ; 208: 111601, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33396121

RESUMEN

Atrazine (ATZ) is among the most widely used herbicides in the world, and yet it has a potential to contaminate aquatic environments due to pesticide leaching from agricultural areas. In the Neotropical region, studies about the effects of this herbicide in native aquatic wildlife is scarce.Our study aimed at investigating the effects of a 30-day exposure to a commercial atrazine formulation on oxidative stress parameters, histopathology in testis and liver, and hormone levels in males and female of yellow-tailed tetra fish (Astyanax altiparanae). Adults were exposed to low but environmentally relevant concentrations of atrazine as follows: 0 (CTL-control), 0.5 (ATZ0.5), 1 (ATZ1), 2 (ATZ2) and 10 (ATZ10) µg/L. Our results showed decreased GST activity in gills in all groups of exposed animals and increased CAT activity in gills from the ATZ10 group. In the liver, there was an increase in lipid peroxidation in fish from ATZ1 and ATZ2 groups. Histological analysis of the liver showed increased percentage of sinusoid capillaries in ATZ2 fish, increased vascular congestion in ATZ1 and increased leukocyte infiltration in the ATZ10 group. Hepatocyte diameter analysis revealed a decrease in cell size in all groups exposed to ATZ, and a decrease in hepatocyte nucleus diameter in ATZ1, ATZ2 and ATZ10 groups. Endocrine parameters did not show significant changes following ATZ exposure, although an increase of triiodothyronine/thyroxine (T3/T4) ratio was observed in ATZ2 fish. Our results provide evidence that even low, environmentally relevant concentrations of ATZ produced oxidative damage and histological alterations in adult yellow-tailed tetra.


Asunto(s)
Atrazina/toxicidad , Characidae/metabolismo , Herbicidas/toxicidad , Estrés Oxidativo/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Animales , Atrazina/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Branquias/efectos de los fármacos , Branquias/metabolismo , Herbicidas/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Testículo/efectos de los fármacos , Testículo/metabolismo , Testículo/patología , Contaminantes Químicos del Agua/metabolismo
2.
Ecotoxicol Environ Saf ; 208: 111731, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33396062

RESUMEN

Cadmium (Cd) is an environmental toxicant and a nonessential metal. Cd can attack a wide range of organs, such as the liver, kidney, lung, ovary, testis, brain, and muscle in vertebrates. Among these organs, the testis might be the most sensitive organ to Cd toxicity. Metallothionein (MT) is a cysteine-rich protein with a low molecular weight, that can bind with Cd and eliminate reactive oxygen species (ROSs). Hydrogen peroxide, which as a crucial type of ROS that is induced by Cd, can be eliminated by catalase (CAT) in the self-protection of cells and to realize Cd toxicity resistance. To investigate the functions of MT and CAT in the testis of Cynops orientalis, we cloned the full-length MT and CAT genes of C. orientalis for the first time. Immunofluorescence results demonstrated that MT and CAT were expressed in Sertoli cells and all spermatogenic cells in the testis of C. orientalis. The results of the ultrastructural damage assay demonstrated that there were various impairments, which included organelle vacuolization, abnormal chromatin distribution, and apoptotic bodies, in somatic cells that were exposed to Cd. However, the anomalies of spermatozoa were located mainly in the mid-piece and head, many of which showed severely impaired structures. The results demonstrated that MT and CAT expression had distinct patterns in response to various Cd concentrations: an increase in MT mRNA levels with elevated Cd levels and a persistent increase in CAT mRNA levels with elevated Cd levels. These results suggested that MT and CAT play roles in Cd toxicity resistance in the testis and that the expression of CAT may be a better biomarker than the expression of MT for assessing Cd pollution.


Asunto(s)
Cadmio/toxicidad , Catalasa/metabolismo , Clonación Molecular , Sustancias Peligrosas/toxicidad , Metalotioneína/metabolismo , Salamandridae/fisiología , Testículo/efectos de los fármacos , Animales , Secuencia de Bases , Humanos , Hígado/metabolismo , Masculino , ARN Mensajero/metabolismo , Salamandridae/genética , Salamandridae/metabolismo , Células de Sertoli/metabolismo , Espermatozoides/metabolismo , Testículo/metabolismo
3.
Ecotoxicol Environ Saf ; 208: 111714, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33396045

RESUMEN

Studies on the effects of unintentional intake of pyrethroid pesticides that are akin to actual human exposure settings are very rare. Such an exposure is primarily by consuming the food products as routine diet that contain residual levels of pyrethroids. In this study, rats were orally administered for 15 months with a mixture of pyrethroids at a dose that is one-fifth (high dose; HD) or one-twenty fifth (low dose; LD) of the residual levels commonly present in the average amount of rice and vegetables consumed by Indian population. Lipid profile, kidney and liver function were assessed. Lipid peroxidation, nitric oxide, antioxidant enzyme activities and histopathological changes were analyzed in the liver, lung, kidney, pancreas, testes, caput, cauda and prostate. The effect on the male reproductive system as a function of sperm count, enzyme activity of 3ß-HSD and 17ß-HSD and the expression profile of genes involved in spermatogenesis, steroidogenesis, genetic reprogramming and apoptosis of male gametes were evaluated. Significant increase in the relative organ weight, perturbations in the activities of antioxidant enzymes, lipid profile and liver function were observed in both LD and HD groups. Damage to the anatomical architecture was evident in all the tissues due to pyrethroid toxicity. Exposure to LD and HD of pyrethroid mixture resulted in decreased sperm count, activities of 3ß-HSD and 17ß-HSD, impaired capacitation and acrosome reaction and perturbations in the expression of genes that govern male gamete production. Results of our study indicate that exposure to pyrethroids for longer durations even at doses that are far below the residual levels present in the food consumed will result in severe damage to general physiological processes as well as reproductive function.


Asunto(s)
Exposición Dietética/efectos adversos , Plaguicidas/toxicidad , Piretrinas/toxicidad , Animales , Antioxidantes/metabolismo , Fertilización/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Tamaño de los Órganos/efectos de los fármacos , Residuos de Plaguicidas/toxicidad , Ratas , Espermatogénesis/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Espermatozoides/metabolismo , Espermatozoides/patología , Testículo/efectos de los fármacos , Testículo/metabolismo , Testículo/patología
4.
Biomed Pharmacother ; 133: 111086, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33378987

RESUMEN

Testicular torsion is an acute urological emergency condition that occurs due to obstruction of blood flow to the testicles which may result in ischemia and loss of testicular functions. This study examined the protective effects of Proxeed Plus (PP), a dietary supplement on testicular ischemia/reperfusion (I/R) injured rats using oxidative stress markers, hormonal levels, apoptotic parameters, histological and immunohistochemistry analysis at 4 h and after 7 days of reperfusion. The protective treatment of the I/R injured rats with PP at 1000 and 5000 mg/kg body weight (bw) resulted in significant increases in the serum and tissue antioxidative defense capacities (superoxide dismutase, reduced glutathione, catalase, glutathione-s-transferase, and glutathione peroxidase), sex hormones (luteinizing hormone, follicle-stimulating hormone, and testosterone), also reduce pro-oxidative markers (malondialdehyde and hydrogen peroxide), serum iNOS and apoptotic parameters (Caspase -3 and Caspase -9) in comparison to the results detected in the I/R untreated rats. It was also observed that PP ameliorated histological changes of I/R injured rats; increased spermatogenetic activity, seminiferous tubular diameter, Leydig cell mass, and reduced expressions of testicular inducible nitric oxide synthase (iNOS). Therefore, the therapeutic use of Proxeed Plus could be considered a promising approach in averting testicular damage against I/R injury.


Asunto(s)
Antioxidantes/farmacología , Suplementos Dietéticos , Inhibidores Enzimáticos/farmacología , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Estrés Oxidativo/efectos de los fármacos , Daño por Reperfusión/prevención & control , Torsión del Cordón Espermático/tratamiento farmacológico , Testículo/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Biomarcadores/sangre , Modelos Animales de Enfermedad , Masculino , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ratas , Ratas Wistar , Daño por Reperfusión/enzimología , Daño por Reperfusión/patología , Transducción de Señal , Torsión del Cordón Espermático/enzimología , Torsión del Cordón Espermático/patología , Espermatogénesis/efectos de los fármacos , Testículo/enzimología , Testículo/patología
5.
Ecotoxicol Environ Saf ; 207: 111537, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33254399

RESUMEN

Despite being an essential trace element with great importance for vital metabolic activities, the manganese (Mn) can also cause damage to organ systems. However, data on the effect of this metal on the male reproductive system are limited, especially using relevant doses to human exposure. The present study aimed to evaluate and compare the effects of Mn exposure on the testicular structure of mice. Three experiments were conducted: (I) direct exposure to realistic doses (0.013, 0.13, and 1.3 mg/kg/day of MnCl2); (II) parental and direct exposure to realistic doses (as in experiment I), where the animals were exposed during intrauterine development and from lactation until reproductive maturity; (III) direct exposure to high doses (15, 30, and 60 mg/kg/day of MnCl2). Biometric, histopathological, histomorphometric and stereological parameters of the testis were evaluated, in addition to sperm morphology. Bioinformatic analyses were performed to identify potential Mn binding sites in 3ß-HSD and P450ssc, as well as their protein-protein interaction network. The results obtained were compared using the integrated biomarker response index (IBR). There was an increase of seminiferous tubules pathologies in all experimental conditions tested, with effects on tubular volume, as well as a reduction in tubular diameter. The IBR analyses showed that parental and direct exposure had a significant negative effect on the testicular structure due to the exposure of this metal to sensitive periods of animal development. This study suggests that Mn has the potential to alter the morphological parameters of the testes, affecting the spermatogenesis in mice.


Asunto(s)
Contaminantes Ambientales/toxicidad , Manganeso/toxicidad , Testículo/anatomía & histología , Animales , Femenino , Lactancia/efectos de los fármacos , Masculino , Ratones , Espermatogénesis/efectos de los fármacos , Testículo/efectos de los fármacos , Pruebas de Toxicidad
6.
Ecotoxicol Environ Saf ; 207: 111563, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33254417

RESUMEN

Exposure to endocrine-disrupting chemicals (EDCs) has been hypothesized as a cause of declining sheep reproductive efficiency. Understanding the long-term effects of EDCs such as heavy metals on reproductive health requires investigation in 'real life' of sheep that are reared in industrial areas. The aim of this study was to evaluate the effect of long-term exposure of Kermani rams to high levels of environmental heavy metals probably emitted from a copper smelter at KhatoonAbad in ShahreBabak, Kerman province. Testicular characteristics were determined in randomly-selected rams (3-4 years old) at 4 directions (south, north, east, and west) and 4 distances (10, 20, 30, and 40 km) from the smelter. Testicular trace element contents, size, serum testosterone, histological attributes and seminal characteristics, except semen volume, were affected by both the direction and the distance from the smelter (P < 0.05). Testicular contents of Pb, Cd, Cr, and Ni, and sperm abnormalities were higher at 10 km south from the smelter and lower at 40 km west. Other parameters were higher at 40 km west and lower at 10 km south. Interestingly, the testicular contents of Cu at 10 km south were lower and associated with higher sperm abnormalities in the rams reared closer to the smelter. The highest weight, length and circumference of the testis were found at 40 km west. The lowest concentration of testosterone was observed at 10 km south, being 92.6% lower than the highest values obtained at 40 km west. The diameter of seminiferous tubules and epithelial height at 10 km south were 8.9% and 27.5% lower than the highest values obtained at 40 km west. A positive correlation between Pb, Cd, Cr and Ni contents in the testis with sperm abnormalities, and a negative correlation between these elements with the other parameters were found. It was concluded that long-term exposure to heavy metals might have been a cause of decreased fertility in rams and probably other living species in this region.


Asunto(s)
Contaminantes Ambientales/toxicidad , Metales Pesados/toxicidad , Testículo/efectos de los fármacos , Animales , Cobre/toxicidad , Masculino , Reproducción , Análisis de Semen/veterinaria , Ovinos , Espermatozoides/efectos de los fármacos , Espermatozoides/fisiología , Testículo/fisiología , Testosterona/sangre , Pruebas de Toxicidad Crónica , Oligoelementos/metabolismo
7.
Chemosphere ; 262: 127880, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32777607

RESUMEN

BACKGROUND: Bisphenol A (BPA) is a well-known endocrine disruptor that affects male fertility. However, the main biological events through which BPA affects spermatogenesis remain to be identified. METHODS: Adult male mice were treated by feeding with drinking water containing BPA (0.2 µg/ml, 20 µg/ml, 200 µg/ml, respectively) for two months. Testes were collected for protein extraction or for immunohistochemical analysis. Epididymal spermatozoa were collected for sperm quality evaluation and male fertility assay by in vitro fertility (IVF). Serums were collected for detection of testosterone levels. Proteins associated with germ cell proliferation, meiosis, blood-testis barrier, and steroidogenesis production were examined in BPA-treated and control mice testes. CCK8 assay was used to detect the effect of BPA on the proliferation of GC-1 and GC-2 cells. RESULTS: The BPA-treated mice were characterized by decreased sperm quality, serum testosterone levels and, sub-fertile phenotype characterizing with low pregnancy rates and reduced fertilization efficiency. In lower BPA (0.2 µg/ml) treatment, PCNA and PLZF were down-expressed that indicated impaired germ cell proliferation. SYCP3 was down-expressed in BPA-treated mice, but expressions of other proteins associated with meiosis and blood-testis barrier were not significantly altered. CYP11A1 and HSD3B1 were down-expressed in BPA-treated mice that demonstrated reduced steroidogenesis activity. BPA has a concentration-dependent inhibition effect on the proliferation of GC-1 and GC-2 cells. Conclusively, low doses BPA exposure reduced mice sperm quality mainly by impairing germ cell proliferation, leading to reduced male fertility. The study would provide relevant information for investigation on molecular mechanisms and protective strategy on male production.


Asunto(s)
Compuestos de Bencidrilo/toxicidad , Disruptores Endocrinos/toxicidad , Fenoles/toxicidad , Espermatozoides/fisiología , Animales , Proliferación Celular/efectos de los fármacos , Disruptores Endocrinos/metabolismo , Epidídimo/efectos de los fármacos , Femenino , Fertilidad/efectos de los fármacos , Masculino , Ratones , Embarazo , Espermatogénesis/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Testículo/efectos de los fármacos , Pruebas de Toxicidad Crónica
8.
Chemosphere ; 262: 127792, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32805656

RESUMEN

Tebuconazole is a triazole fungicide, used in agriculture to treat phytopathogenic fungi, and as a biocide, has been reported to be related to reproductive and developmental toxicity. The purpose of this study was to investigate the effect of tebuconazole exposure on rat fetal Leydig cells and fetal testis during pregnancy. Pregnant Sprague-Dawley rats were randomly divided into 4 groups, daily gavaged with corn oil (as a control), 25, 50, and 100 mg/kg body weight tebuconazole for 10 days (from the 12th day of pregnancy). Tebuconazole increased fetal serum testosterone and progesterone levels at a dose of 100 mg/kg. Exposure to 100 mg/kg tebuconazole significantly caused an increase in the number of fetal Leydig cells per testis without inducing cell aggregation. Tebuconazole up-regulated the expression of Star, Cyp11a1, Hsd17b3, and Fshr and their proteins. Further investigation found that tebuconazole caused increased phosphorylation of AKT1, ERK1/2, and mTOR, the level of BCL2, as well as the decrease of Beclin1, LC3B, and BAX, which may contribute to the fetal Leydig cell autophagy and proliferation. In conclusion, in utero exposure of tebuconazole causes the proliferation of fetal Leydig cells.


Asunto(s)
Fungicidas Industriales/toxicidad , Células Intersticiales del Testículo/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Reproducción/efectos de los fármacos , Triazoles/toxicidad , Animales , Femenino , Células Intersticiales del Testículo/metabolismo , Masculino , Fosfoproteínas/genética , Fosforilación , Embarazo , Efectos Tardíos de la Exposición Prenatal/patología , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Testículo/efectos de los fármacos , Testículo/embriología , Testículo/patología , Testosterona/sangre , Regulación hacia Arriba
9.
Aquat Toxicol ; 231: 105722, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33360311

RESUMEN

The current study investigated the effect of environmentally relevant mixtures of estrogens at levels representative of receiving waters on the metabolome of the Sydney rock oyster, Saccostrea glomerata. Oysters were exposed to a "low" and a "high" mixture of (xeno) estrogens (representative of Australian and global receiving waters respectively) for 7 days and digestive gland, gill, and gonad tissue were sampled for quantification of polar metabolites by 1H NMR spectroscopy. Exposure to both mixtures lowered body mass and altered the metabolite profile in the digestive glands. Comparatively, gills, and ovaries demonstrated lesser sensitivity to the mixtures, with significant metabolomic alterations observed only for the high mixture. The male gonad did not respond to either estrogenic exposure. In the responsive tissues, major metabolites including amino acids, carbohydrates, intermediates of the tricarboxylic acid cycle and ATP were all down-regulated and exhibited tissue-specific patterns of down-regulation with the greatest proportion of metabolites down-regulated due to estrogenic exposure in the digestive gland. Exposure to (xeno) estrogen mixtures representative of concentrations reported in receiving waters in Australia and globally can impact the metabolome and associated energy metabolism, especially in the digestive gland, translating to lower pools of available ATP energy for potential cellular homeostasis, somatic maintenance and growth, reproduction and fitness.


Asunto(s)
Exposición a Riesgos Ambientales , Estrógenos/toxicidad , Metaboloma/efectos de los fármacos , Especificidad de Órganos , Ostreidae/metabolismo , Animales , Australia , Peso Corporal/efectos de los fármacos , Ciclo del Ácido Cítrico/efectos de los fármacos , Femenino , Glucólisis/efectos de los fármacos , Masculino , Metabolómica , Ostreidae/efectos de los fármacos , Ovario/efectos de los fármacos , Ovario/metabolismo , Razón de Masculinidad , Testículo/efectos de los fármacos , Testículo/metabolismo , Contaminantes Químicos del Agua/toxicidad
10.
Ecotoxicol Environ Saf ; 209: 111798, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33360214

RESUMEN

Di-(2-ethylhexyl) phthalate (DEHP), one of the most commonly used endocrine-disrupting chemicals, has been shown to cause reproductive dysfunction in humans and animal models. However, very few studies have investigated the impact of DEHP at the post-transcriptional level in mouse testes, and the underlying mechanisms remain unclear. In the present research, TM3 Leydig cells were treated with 200 µM phthalic acid mono-2-ethylhexyl ester (MEHP, bio-metabolite of DEHP), and then the mRNA and lncRNA sequencing of TM3 Leydig cells was performed. Mice were exposed prepubertally to 0 or 500 mg DEHP/kg/day. RNA sequencing of mouse testes was performed to verify the RNA-seq results in vitro. The expression patterns of relevant genes and proteins were verified using real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. DEHP and MEHP exposure led to testicular damage and accelerated cell aging via ROS accumulation. RNA sequencing analyses indicated that FOXO signaling and longevity regulation pathways were activated in resistance to ROS accumulation. FOXO signaling and longevity regulation pathway-related genes and proteins were also activated. By constructing a competing endogenous RNA (ceRNA) network, we observed that the ceRNA network might play a role in regulating FOXO signaling and longevity regulation pathways in response to excessive ROS accumulation and cell aging. In summary, our data here suggests that the ceRNA network may play a role in regulating FOXO signaling and longevity pathways in response to DEHP exposure in mouse testes.


Asunto(s)
Dietilhexil Ftalato/toxicidad , Disruptores Endocrinos/toxicidad , ARN Largo no Codificante/metabolismo , Envejecimiento , Animales , Dietilhexil Ftalato/metabolismo , Disruptores Endocrinos/metabolismo , Regulación de la Expresión Génica , Humanos , Células Intersticiales del Testículo/efectos de los fármacos , Células Intersticiales del Testículo/metabolismo , Longevidad , Masculino , Ratones , Ácidos Ftálicos , Testículo/efectos de los fármacos , Transcriptoma
11.
Ecotoxicol Environ Saf ; 209: 111783, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33383340

RESUMEN

Decabromodiphenyl ether (BDE-209) is widely used as a flame retardant in many products like electronic equipments, plastics, furniture and textiles. BDE-209, a thyroid hormones (THs)-disrupting chemical, affects male reproductive health through altered THs status in mouse model. The present study was designed in continuation to our earlier work to elucidate whether early life exposure to BDE-209 has a long term potential risk to male reproductive health. This study, therefore, aimed to evaluate the effect of maternal BDE-209 exposure during lactation and to elucidate possible mechanism(s) of its action on male reproduction in adult Parkes mice offspring. Lactating female Parkes mice were orally gavaged with 500, and 700 mg/kg body weight of BDE-209 in corn oil from postnatal day (PND) 1 to PND 28 along with 6-propyl-2-thiouracil (PTU)-treated positive controls and vehicle-treated controls. Male pups of lactating dams were euthanized at PND 75. Maternal BDE-209 exposure during lactation markedly affected histoarchitecture of testis and testosterone production with concomitant down-regulation in the expression of various steroidogenic markers in adult offspring. Maternal exposure to BDE-209 during lactation also interfered with germ cell dynamics and oxidative status in testes of adult mice offspring. A decreased expression of connexin 43 and androgen receptor was also evident in testes of these mice offspring; further, number, motility and viability of spermatozoa were also adversely affected in these mice. The results thus provide evidences that maternal exposure to BDE-209 during lactation causes reproductive toxicity in adult mice offspring.


Asunto(s)
Retardadores de Llama/toxicidad , Éteres Difenilos Halogenados/toxicidad , Espermatogénesis/efectos de los fármacos , Animales , Conexina 43/metabolismo , Femenino , Células Germinativas/efectos de los fármacos , Lactancia/efectos de los fármacos , Masculino , Exposición Materna , Ratones , Receptores Androgénicos/metabolismo , Espermatozoides/efectos de los fármacos , Esteroides/metabolismo , Testículo/efectos de los fármacos , Testosterona/metabolismo , Hormonas Tiroideas/metabolismo
12.
Zhonghua Nan Ke Xue ; 26(2): 111-117, 2020 Feb.
Artículo en Chino | MEDLINE | ID: mdl-33346412

RESUMEN

Objective: To study the effect of different levels of autophagy in the testis on the apoptosis of spermatogenic cells in the rat model of varicocele (VC). METHODS: We randomly divided 54 SD male rats into six groups, blank control (n = 6), rapamycin control (n = 6), chloroquine control (n = 6), VC model control (n = 12), VC + rapamycin (n = 12), and VC + chloroquine (n = 12). We observed the histomorphological changes of the testis and epididymis by HE staining, obtained the scores on spermatogenesis in the testis and epididymis, calculated the apoptosis index (AI) of the testicular spermatogenic cells by TUNEL, and determined the expressions of LC3-Ⅱ, LC3-Ⅰ, p62, Bax and Bcl-2 proteins in the testis tissue by Western blot. RESULTS: There were no significant morphological changes in the testis and epididymis of the rats in the blank control, rapamycin control and chloroquine control groups, or significant differences in the scores on testicular and epididymal spermatogenesis and AI of the testicular spermatogenic cells (P>0.05). The animals in the VC model control group exhibited significant pathological damage in the testicular and epididymal tissues, with remarkably decreased scores on spermatogenesis (P<0.01) and increased AI (P<0.01), which were markedly improved in the VC + rapamycin group and slightly aggravated in the VC + chloroquine group compared with the VC model controls. In comparison with the rats in the blank control group, those in the VC model control group showed significantly up-regulated expressions of the autophagy-related protein LC3 (including the LC3-Ⅱ/LC3-Ⅰ ratio) and the pro-apoptotic protein Bax in testicular tissue (P<0.01) but down-regulated expression of the anti-apoptotic protein Bcl-2 (P<0.01). The expressions of LC3 and Bcl-2 in the testis tissue were significantly higher in the VC + rapamycin (P<0.01) but lower in the VC + chloroquine group (P<0.01), while those of p62 and Bax remarkably lower in the VC + rapamycin (P<0.01) but higher in the VC + chloroquine group than in the VC model controls (P<0.01). CONCLUSIONS: Varicocele induces autophagy in the testis and apoptosis of spermatogenic cells in rats. Up-regulating autophagy can inhibit while blocking autophagy can promote the apoptosis of spermatogenic cells.


Asunto(s)
Autofagia , Células Germinativas/citología , Espermatogénesis , Testículo/citología , Varicocele/fisiopatología , Animales , Apoptosis , Masculino , Ratas , Ratas Sprague-Dawley , Testículo/efectos de los fármacos
13.
Zhonghua Nan Ke Xue ; 26(2): 160-166, 2020 Feb.
Artículo en Chino | MEDLINE | ID: mdl-33346421

RESUMEN

Objective: To investigate the protective effect of Jinkui Shenqi Pills (JSP) against cyclophosphamide-induced testis injury (TI) and its anti-oxidation mechanism in mice. METHODS: Thirty male mice were equally divided into a blank control, a TI model control and a JSP treatment group. The mice in the JSP treatment group were treated intragastrically with JSP and the blank controls with normal saline at 1.2 g/kg qd for 7 days, and then the animals in both the TI model control and JSP treatment groups were injected intraperitoneally with cyclophosphamide at 50 mg/kg, once a week, for 35 days, to induce testis injury. After modeling, all the mice were weighed and sacrificed, followed by detection of the serum T content, measurement of the testis weight, examination of semen parameters in the caudad epididymis, and determination of the levels of super oxide dismutase (SOD) and malondialdehyde (MDA) in the testis tissue and the expressions of relevant genes by qRT-PCR. RESULTS: The mice of the TI model control group, compared with the blank controls, showed significant decreases in the body weight (ï¼»34.63 ± 1.92ï¼½ vs ï¼»48.32 ± 1.64ï¼½ g, P<0.05), testis weight (ï¼»80.00 ± 3.90ï¼½ vs ï¼»140.00 ± 6.10ï¼½ mg, P<0.05), testicular organ coefficient (ï¼»0.22 ± 0.01ï¼½ vs ï¼»0.31 ±0.03ï¼½%, P<0.05), sperm motility (ï¼»48.66 ± 8.08ï¼½% vs ï¼»89.33 ± 4.04ï¼½%, P<0.05), sperm concentration (ï¼»28.42 ± 5.26ï¼½ vs ï¼»77.67 ± 8.73ï¼½ ×106/ml, P<0.05), and levels of serum T (ï¼»8.75 ± 0.96ï¼½ vs ï¼»21.75 ± 1.71ï¼½ pg/ml, P<0.05) and SOD (ï¼»140.82 ± 10.08ï¼½ vs ï¼»358.52 ± 40.41ï¼½ U/mg prot, P<0.05), but remarkable increases in the sperm deformity rate (ï¼»37.33 ± 2.08ï¼½ vs ï¼»15.33±1.53ï¼½%, P<0.05) and MDA level (ï¼»54.89±6.09ï¼½ vs ï¼»30.21±2.17ï¼½ nmol/ng prot, P<0.05). The mice of the JSP treatment group, in comparison with the TI model controls, exhibited markedly increased body weight (ï¼»39.80±2.89ï¼½ vs ï¼»34.63±1.92ï¼½g, P<0.05), testis weight (ï¼»130.00 ± 11.00ï¼½ vs ï¼»80.00 ± 3.90ï¼½ mg, P<0.05), testicular organ coefficient (ï¼»0.28 ± 0.01ï¼½ vs ï¼»0.22 ± 0.01ï¼½%, P<0.05), sperm motility (ï¼»76.00 ± 5.29ï¼½% vs ï¼»48.66 ± 8.08ï¼½%, P<0.05), sperm concentration (ï¼»56.08 ± 4.29ï¼½ vs ï¼»28.42 ± 5.26ï¼½ ×106/ml, P<0.05), and levels of serum T (ï¼»15.50 ± 1.29ï¼½ vs ï¼»8.75 ± 0.96ï¼½ pg/ml, P<0.05) and SOD (ï¼»206.59 ± 16.38ï¼½ vs ï¼»140.82 ± 10.08ï¼½ U/mg prot, P<0.05), but decreased sperm deformity rate (ï¼»25.01 ± 2.99ï¼½% vs ï¼»37.33 ± 2.08ï¼½%, P<0.05) and MDA level (ï¼»35.84 ± 3.61ï¼½ vs ï¼»54.89 ± 6.09ï¼½ nmol/ng prot, P<0.05). The mRNA expressions of NOQ-1, Nrf2 and HO-1 in the testis tissue were significantly lower and that of Caspase-3 remarkably higher in the TI model control than in the blank control group (P<0.05), while those of Nrf2 and HO-1 significantly higher and that of Caspase-3 markedly lower in the JSP treatment group than in the TI model controls (P<0.05). Histopathological images displayed reduced layers of spermatogenic cells in the seminiferous tubules, complete exfoliation of the spermatogenic cells in some of the tubules and decreased number of sperm cells in the TI model controls, which were all found normal in the JSP treatment group. CONCLUSIONS: Jinkui Shenqi Pills can effectively inhibit cyclophosphamide-induced testis injury, which may be related to its effect of regulating the gene expression of the Nrf2 signaling pathway and enhancing the activity of antioxidant enzymes.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Motilidad Espermática , Testículo/metabolismo , Animales , Ciclofosfamida , Expresión Génica , Masculino , Ratones , Factor 2 Relacionado con NF-E2/genética , Transducción de Señal , Recuento de Espermatozoides , Espermatozoides , Testículo/efectos de los fármacos
14.
Zhonghua Nan Ke Xue ; 26(3): 237-241, 2020 Mar.
Artículo en Chino | MEDLINE | ID: mdl-33346963

RESUMEN

Objective: To investigate the effect of Jiarong Tablets (JRT) on the testicular morphology and function of rats with late-onset hypogonadism (LOH). METHODS: LOH models were established in 8 eighteen-month-old male SD rats, treated intragastrically with distilled water (the model control group, n = 4) or JRT at 0.375 g/kg/d, qd (the JRT group, n = 4), and another 5 two-month-old normal male SD rats were also given distilled water by gavage (normal control group), all for 28 days. Then all the rats were weighed and sacrificed for measurement of the serum T level and pathological and electron microscopic examination of the testis tissue. RESULTS: Compared with the normal controls, the LOH models showed significantly decreased testis coefficient (P < 0.05) and serum T level (ï¼»3.40 ± 0.06ï¼½ vs ï¼»5.88 ± 0.46ï¼½ ng /ml, P < 0.05). No statistically significant differences were observed in the model control and JRT groups in the body weight and testis coefficient (P > 0.05), but the serum T level (ï¼»4.50 ± 0.78ï¼½ ng/ml) was remarkably decreased in the latter (P < 0.05). In comparison with the model controls, the rats treated with JRT exhibited increases in the sperm count in the seminiferous tubules and the amount of testicular interstitial cells. Electron microscopy revealed a markedly increased number of mitochondria in the JRT-treated animals, with some mitochondrial sheaths and cristae but no obvious mitochondrial edema. CONCLUSIONS: Jiarong Tablets can elevate the serum T level and improve the testicular morphology and ultrastructure of LOH rats.


Asunto(s)
Medicamentos Herbarios Chinos , Hipogonadismo , Testículo/efectos de los fármacos , Animales , Medicamentos Herbarios Chinos/farmacología , Hipogonadismo/tratamiento farmacológico , Masculino , Ratas , Ratas Sprague-Dawley , Recuento de Espermatozoides , Comprimidos , Testículo/anatomía & histología , Testosterona/sangre
15.
Zhonghua Nan Ke Xue ; 26(5): 457-463, 2020 May.
Artículo en Chino | MEDLINE | ID: mdl-33354957

RESUMEN

Objective: To investigate the improving effect of Duzhong Butiansu Capsules (DBC) on the fertility of male mice. METHODS: Forty-eight 4-week-old SPF male Kunming mice weighing 12-16 g were randomly divided into four groups of equal number, distilled water (DW) control, Shengjing Capsules (SJC), low-dose DBC and high-dose DBC, treated intragastrically with distilled water, SJC at 0.8 g/kg/d, DBC at 0.694 g/kg/d and DBC at 1.388 g/kg/d, respectively, all for 3 weeks. After 2 weeks of treatment, the male mice were mated with female ones at a 2∶1 ratio for 1 week. Then, all the male animals were sacrificed for observation of the morphological changes in the testis and epididymis by HE staining, detection of the sperm count and motility, coefficients of different organs and expression of the androgen receptor (AR) in the testis, measurement of the levels of E2, LH, FSH and T by ELISA, and determination of the concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (Cr) and urea nitrogen (BUN) in the serum. At 1 week after mating, the female mice were executed and the number of pregnancies recorded. RESULTS: The pregnancy rate was significantly higher in the low- and high-dose DBC groups (70% and 75%) than in the DW control (54%). The weight-bearing swimming time was markedly longer in the low-dose DBC than in the DW control group (ï¼»394 ± 51ï¼½ vs ï¼»173 ± 17ï¼½ s, P < 0.01) but exhibited no statistically significant difference between the high-dose DBC (ï¼»266 ± 42ï¼½ s) and the latter groups (P > 0.05). Remarkable increases were observed in the low-dose DBC group, compared with the DW control group, in the counts of spermatogonia (77.8 ± 5.0 vs 25.7 ± 5.3, P < 0.01), spermatocytes (132.4 ± 8.9 vs 92.5 ± 10.7, P < 0.01) and mature sperm (734 ± 67 vs 481 ± 56, P < 0.01), as well as in both the low- and high-dose DBC groups in the AR expression (P < 0.01). The AST concentration was markedly higher in the high-dose DBC than in the DW control group (ï¼»44.2 ± 11.0ï¼½ vs ï¼»30.5 ± 13.7ï¼½ U/L, P < 0.05), but there were no statistically significant differences between the DW control and the low- or high-dose DBC groups in the levels of serum T, FSH, LH, E2, Cr and BUN (P > 0.05). CONCLUSIONS: Duzhong Butiansu Capsules could improve the fertility of male mice, which has provided some experimental evidence for the clinical application of the medicine.


Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Epidídimo , Fertilidad/efectos de los fármacos , Motilidad Espermática , Testículo , Animales , Cápsulas , Epidídimo/efectos de los fármacos , Femenino , Masculino , Ratones , Embarazo , Distribución Aleatoria , Recuento de Espermatozoides , Espermatozoides , Testículo/efectos de los fármacos
16.
PLoS One ; 15(12): e0242218, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33370316

RESUMEN

Improvements in survival rates with gonad-sparing protocols for childhood and adolescence cancer have increased the optimism of survivors to become parents after treatment. Findings in rodents indicate that chromosomal aberrations can be induced in male germ cells by genotoxic exposures and transmitted to offspring and future generations with effects on development, fertility and health. Thus, there is a need for effective technologies to identify human sperm carrying chromosomal aberrations to assess the germ-line risks, especially for cancer survivors who have received genotoxic therapies. The time-dependent changes in the burden of sperm carrying structural chromosomal aberrations were assessed for the first time in a cancer setting, using the AM8 sperm FISH protocol which simultaneously detects abnormalities in chromosomal structure and number in sperm. Nine Hodgkin lymphoma (HL) patients provided 20 semen samples before, during, and after NOVP therapy (Novantrone, Oncovin, Velban and Prednisone) and radiation therapy that produced scattered gonadal doses from <0.05 to 0.6 Gy. Late meiosis was found to be the most sensitive to NOVP treatment for the production of sperm with chromosomal abnormalities, both in structure and number. Earlier stages of spermatogenesis were less sensitive and there was no evidence that therapy-exposed stem cells resulted in increased frequencies of sperm with abnormalities in chromosomal structure or number. This indicates that NOVP therapy may increase the risks for paternal transmission of chromosomal structural aberrations for sperm produced 32 to 45 days after a treatment with these drugs and implies that there are no excess risks for pregnancies conceived more than 6 months after this therapy. This clinical evaluation of the AM8 sperm FISH protocol indicates that it is a promising tool for assessing an individual's burden of sperm carrying chromosomal structural aberrations as well as aneuploidies after cancer therapy, with broad applications in other clinical and environmental situations that may pose aneugenic or clastogenic risks to human spermatogenesis.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Aberraciones Cromosómicas/efectos de los fármacos , Enfermedad de Hodgkin/terapia , Meiosis/efectos de los fármacos , Análisis de Semen/métodos , Espermatozoides/efectos de los fármacos , Adulto , Células Madre Germinales Adultas/efectos de los fármacos , Células Madre Germinales Adultas/efectos de la radiación , Supervivientes de Cáncer , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Aberraciones Cromosómicas/efectos de la radiación , Estudios de Cohortes , Preservación de la Fertilidad , Humanos , Hibridación Fluorescente in Situ/métodos , Masculino , Meiosis/efectos de la radiación , Mitoxantrona/efectos adversos , Mutagénesis/efectos de los fármacos , Mutagénesis/efectos de la radiación , Tratamientos Conservadores del Órgano/efectos adversos , Tratamientos Conservadores del Órgano/métodos , Órganos en Riesgo/efectos de la radiación , Prednisona/efectos adversos , Dosificación Radioterapéutica , Espermatogénesis/efectos de los fármacos , Espermatogénesis/efectos de la radiación , Espermatozoides/fisiología , Espermatozoides/efectos de la radiación , Testículo/efectos de los fármacos , Testículo/efectos de la radiación , Factores de Tiempo , Vinblastina/efectos adversos , Vincristina/efectos adversos
17.
Zhonghua Nan Ke Xue ; 26(9): 777-782, 2020 Sep.
Artículo en Chino | MEDLINE | ID: mdl-33377698

RESUMEN

Objective: To study the effect of taurine on the reproductive toxicity damage induced by formaldehyde (FM) in adult male rats. METHODS: Forty-eight SD adult male rats were equally randomized into a normal control, an FM poisoning (FMP), a taurine intervention (TI), and an TI+FMP group. The control rats were given normal diet and gavage of saline, the rats of the FMP group treated intraperitoneally with FM at 10 mg/kg qd alt, those of the TI group intragastrically with taurine at 100 mg/kg qd, and those of the TI+FMP group with both FM and taurine at the above doses. After 30 days of treatment, the blood of the abdominal cardinal vein of the rats was extracted for measurement of the levels of serum hormones, the body weight, testis weight and testicular coefficient obtained, the testis tissue subjected to HE staining, and the expressions of Bcl-2 and Bax determined by Western blot. RESULTS: There were no statistically significant differences among the four groups of rats in the body weight, testis weight or testicular coefficient (P > 0.05). The rats in the FMP group showed obviously decreased testicular spermatogenic cells and disordered layers and loose structure of seminiferous tubules, which were basically restored to normal after taurine intervention. Compared with the normal controls, the animals of the TI group exhibited no significant abnormality, but those of the FMP group presented markedly reduced levels of serum T, LH and FSH (P < 0.05), and dramatically increased level of Gonadotropin-releasing hormone (GnRH) (P < 0.01). The levels of serum hormones were all significantly improved (P < 0.05) and that of the apoptotic protein Bax basically returned to normal (P < 0.05) after taurine intervention. CONCLUSIONS: Taurine has a certain protective effect against male reproductive toxicity caused by formaldehyde.


Asunto(s)
Formaldehído/toxicidad , Taurina/uso terapéutico , Testículo/efectos de los fármacos , Animales , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Túbulos Seminíferos/efectos de los fármacos , Túbulos Seminíferos/patología , Testículo/patología
18.
Zhonghua Nan Ke Xue ; 26(9): 826-831, 2020 Sep.
Artículo en Chino | MEDLINE | ID: mdl-33377708

RESUMEN

Objective: To investigate the effect of Bushen Huoxue Recipe (BHR) on cyclophosphamide-induced apoptosis of testicular spermatogenic cells in mice and its possible action mechanisms. METHODS: Fifty male Babl/c mice aged 8-9 weeks were randomly divided into five groups of an equal number: blank control, model control, low-dose BHR, medium-dose BHR and high-dose BHR. The animals in the blank control group were intraperitoneally injected with normal saline, while those in the other four groups with cyclophosphamide at 50 mg/kg/d, all for 7 days. After modeling, the mice in the blank and model control groups were given distilled water via gavage once a day, and those in the low-, medium- and high-dose BHR groups treated intragastrically with BHR at 7.5, 15 and 30 g/kg/d qd for 30 successive days. Then, the apoptosis index of the testicular spermatogenic cells was obtained by TUNEL and the expressions of Bax and Bcl-2 mRNA and proteins determined by RT-PCR and Western blot, respectively. RESULTS: Compared with the mice in the blank control group, the BHR model controls showed dramatically increased apoptosis of testicular spermatogenic cells and up-regulated mRNA and protein expressions of Bax and Bcl-2 in the testis tissue (P < 0.01). In comparison with the model controls, the mice in the BHR treatment groups exhibited significantly reduced apoptosis of testicular spermatogenic cells and down-regulated mRNA and protein expressions of Bax and Bcl-2 in the testis tissue (P < 0.01). CONCLUSIONS: Bushen Huoxue Recipe can reduce cyclophosphamide-induced apoptosis of testicular spermatogenic cells in mice, which may be associated with its ability of regulating the expressions of Bax and Bcl-2 mRNA and proteins in the testis tissue.


Asunto(s)
Apoptosis , Medicamentos Herbarios Chinos/farmacología , Testículo/efectos de los fármacos , Animales , Ciclofosfamida/toxicidad , Masculino , Ratones , Ratones Endogámicos BALB C , Distribución Aleatoria , Testículo/patología
19.
Zhonghua Nan Ke Xue ; 26(10): 926-933, 2020 Nov.
Artículo en Chino | MEDLINE | ID: mdl-33382226

RESUMEN

Objective: To investigate the relationship of electromagnetic radiation (EMR) from 900 MHz cellphone frequency with testicular oxidative damage and its influence on the Prdx2 protein expression in the rat testis, and to explore the mechanism of Guilingji Capsules (GC) alleviating oxidative damage to the testis tissue. METHODS: Fifty healthy SD male rats were randomly divided into five groups of equal number, sham-EMR, 4-h EMR, 8-h EMR, 4-h EMR+GC and 8-h EMR+GC and exposed to 900 MHz EMR (370 µW/cm2) for 0, 4 or 8 hours daily for 15 successive days. The rats of the latter two groups were treated intragastrically with GC suspension and those of the first three groups with pure water after exposure to EMR each day. After 15 days of exposure and treatment, all the rats were sacrificed and their testis tissue collected for observation of the histomorphological and ultrastructural changes by HE staining and transmission electron microscopy, measurement of the levels of serum glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) with thiobarbiuric acid and determination of the Prdx2 protein expression by immunohistochemistry and Western blot. RESULTS: Compared with the rats in the sham-EMR group, those in the 4-h and 8-h EMR groups showed different degrees of histomorphological and ultrastructural changes in the testis tissue, significantly decreased levels of GSH (ï¼»80.62 ± 10.99ï¼½ vs ï¼»69.58 ± 4.18ï¼½ and ï¼»66.17 ± 8.45ï¼½ mg/L, P < 0.05) and SOD (ï¼»172.29 ± 10.98ï¼½ vs ï¼»158.92 ± 6.46ï¼½ and ï¼»148.91 ± 8.60ï¼½ U/ml, P < 0.05) and increased level of MDA (ï¼»7.51 ± 1.73ï¼½ vs ï¼»9.84 ± 1.03ï¼½ and ï¼»11.22 ± 2.13ï¼½ umol/ml, P < 0.05), even more significantly in the 8-h than in the 4-h EMR group (P < 0.05). In comparison with the sham-EMR group, the expression of the Prdx2 protein was markedly downregulated in the 4-h and 8-h EMR groups (0.56 ± 0.03 vs 0.49 ± 0.03, 0.21 ± 0.01, P < 0.05), but again upregulated in the 4-h and 8-h EMR+GC groups (0.55±0.03 and 0.37±0.04) (P < 0.05). CONCLUSIONS: Electromagnetic radiation from cellphones can cause ultrastructural damage to the testis tissue of male rats, while Guilingji Capsules can alleviate it, presumably by upregulating the Prdx2 protein expression in the testis tissue and reducing testicular oxidative damage.


Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Radiación Electromagnética , Estrés Oxidativo , Peroxirredoxinas/metabolismo , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Testículo , Animales , Cápsulas , Teléfono Celular , Glutatión/sangre , Masculino , Malondialdehído/sangre , Microscopía Electrónica de Transmisión , Ratas , Superóxido Dismutasa/sangre , Testículo/efectos de los fármacos , Testículo/metabolismo , Testículo/patología , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis
20.
Zhonghua Nan Ke Xue ; 26(7): 639-644, 2020 Jul.
Artículo en Chino | MEDLINE | ID: mdl-33377721

RESUMEN

Objective: To investigate the effect of Cuscuta chinensis flavonoids (CCF) on the expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) in the testis of the rat with oligozoospermia (OZ). METHODS: Thirty SD male rats were randomly divided into three groups of equal number, blank control, OZ model control and CCF intervention. The OZ model was established in the latter two groups by intraperitoneal injection of cyclophosphamide at 30 mg/kg qd for 5 successive days. From the 6th day, the rats in the CCF intervention group were treated intragastrically with mixed suspension of CCF at 5 mL/kg and those in the other two groups with normal saline, all for 4 weeks. The epididymal sperm concentration and motility and the testicular morphology were examined and the expression of GM-CSF in the testis tissue detected with the SELDI Protein Chip. RESULTS: Compared with the rats in the blank control and CCF intervention groups, the OZ model controls showed dramatically decreased epididymal sperm concentration and motility (both P < 0.01) and significant morphological changes in the testis with deformed seminiferous tubules and reduced number and disordered arrangement of spermatogenic cells. Normal testicular morphology was observed in the CCF intervention group and there were no statistically significant differences in sperm concentration and motility between the CCF intervention and blank control groups (P > 0.05). The expression of GM-CSF was significantly up-regulated in the testis tissue of the OZ model controls but lower than the minimum value obtained with the SELDI Protein Chip in the blank control and CCF intervention groups. CONCLUSIONS: Cuscuta chinensis flavonoids can significantly down-regulate the expression of GM-CSF in the testis of the rats with cyclophosphamide-induced oligozoospermia.


Asunto(s)
Cuscuta/química , Flavonoides/farmacología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Oligospermia , Testículo/efectos de los fármacos , Animales , Masculino , Oligospermia/inducido químicamente , Oligospermia/tratamiento farmacológico , Fitoquímicos/farmacología , Ratas , Ratas Sprague-Dawley , Espermatozoides , Testículo/metabolismo
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