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1.
Int J Mol Sci ; 22(5)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802611

RESUMO

The objective of this work has been to characterize the estrogenic activity of bisphenol-A (BPA) and the adverse effects on the endocannabinoid system (ECS) in modulating germ cell progression. Male offspring exposed to BPA during the foetal-perinatal period at doses below the no-observed-adverse-effect-level were used to investigate the exposure effects in adulthood. Results showed that BPA accumulates specifically in epididymal fat rather than in abdominal fat and targets testicular expression of 3ß-hydroxysteroid dehydrogenase and cytochrome P450 aromatase, thus promoting sustained increase of estrogens and a decrease of testosterone. The exposure to BPA affects the expression levels of some ECS components, namely type-1 (CB1) and type-2 cannabinoid (CB2) receptor and monoacylglycerol-lipase (MAGL). Furthermore, it affects the temporal progression of germ cells reported to be responsive to ECS and promotes epithelial germ cell exfoliation. In particular, it increases the germ cell content (i.e., spermatogonia while reducing spermatocytes and spermatids), accelerates progression of spermatocytes and spermatids, promotes epithelial detachment of round and condensed spermatids and interferes with expression of cell-cell junction genes (i.e., zonula occcludens protein-1, vimentin and ß-catenin). Altogether, our study provides evidence that early exposure to BPA produces in adulthood sustained and site-specific BPA accumulation in epididymal fat, becoming a risk factor for the reproductive endocrine pathways associated to ECS.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/metabolismo , Endocanabinoides/metabolismo , Epididimo/efeitos dos fármacos , Estrogênios/metabolismo , Células Germinativas/efeitos dos fármacos , Fenóis/efeitos adversos , Fenóis/metabolismo , Tecido Adiposo/metabolismo , Animais , Sistema Endócrino/efeitos dos fármacos , Sistema Endócrino/metabolismo , Epididimo/metabolismo , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Células Germinativas/metabolismo , Junções Intercelulares/efeitos dos fármacos , Junções Intercelulares/metabolismo , Masculino , Camundongos , Fatores de Risco , Testosterona/metabolismo
2.
Methods Mol Biol ; 2240: 65-76, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33423227

RESUMO

Contraction of cauda epididymal duct (CE) smooth muscle is one of the very first events of the seminal emission phase of ejaculation. The contraction of CE smooth muscle is governed by a complex interaction of hormones, autacoids, and by the neurotransmitters released from the epididymal intramural nerve endings, and any impairment in the CE smooth muscle contraction has the potential to impair male fertility. Apart the obvious pathophysiological and toxicological importance of CE smooth muscle contraction, modulation of CE contraction has pharmaceutical interest offering a druggable target to development of drugs to improve/impair male fertility. The in vitro contraction experiments constitute a valuable approach to an in-depth evaluation of functional and molecular changes resulting from pathologies or drug exposure. Therefore, this chapter consists in a description of in vitro pharmacological reactivity contractility of the epididymal duct in a controlled medium, maintained at 30 °C of temperature and continuously bubbled with 95% O2 and 5% CO2 to obtain cumulative concentration-response curves that has been fundamental to some of our investigations on epididymal physiology, toxicology, and pharmacology.


Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Epididimo/efeitos dos fármacos , Fármacos para a Fertilidade Masculina/farmacologia , Contração Muscular , Animais , Avaliação Pré-Clínica de Medicamentos/instrumentação , Epididimo/fisiologia , Masculino , Músculo Liso/fisiologia , Ratos
3.
Chemosphere ; 262: 127880, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32777607

RESUMO

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.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Fenóis/toxicidade , Espermatozoides/fisiologia , Animais , Proliferação de Células/efeitos dos fármacos , Disruptores Endócrinos/metabolismo , Epididimo/efeitos dos fármacos , Feminino , Fertilidade/efeitos dos fármacos , Masculino , Camundongos , Gravidez , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testes de Toxicidade Crônica
4.
Gene ; 766: 145155, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32950634

RESUMO

Expression of browning genes are lower in both humans and animals with type 2 diabetes (T2D). This study aims at determining effects of long-term nitrate administration on protein and mRNA levels of uncoupling protein 1 (UCP1), peroxisome proliferator activated receptor gamma (PPAR-γ), and PPAR-γ coactivator 1 alpha (PGC1-α) in epididymal adipose tissue (eAT) of rats with T2D. Male Wistar rats were divided into 4 groups (n = 6/group): Control, diabetes, control + nitrate (CN), and diabetes + nitrate (DN). T2D was induced using high fat diet combined with a low-dose of streptozotocin (30 mg/kg body weight). Sodium nitrate was administrated at a dose of 100 mg/L for 6 months in nitrate-treated rats. Fasting serum glucose and insulin concentrations were measured at months 0 (i.e. at start of the protocol), 3, and 6. At month 6, protein and mRNA levels of UCP1, PPAR-γ, and PGC1-α were measured in eAT samples. In addition, tissue concentration of cyclic guanosine monophosphate (cGMP) was measured and histological analyses were done at month 6. In rats with T2D, 6-month administration of nitrate decreased serum glucose and insulin concentrations by 13% and 23%, respectively and increased cGMP level by 85%. Rats with T2D had lower mRNA and protein levels of PPAR-γ (62%, P < 0.0001 and 18%, P = 0.0472), PGC1-α (49%, P = 0.0019 and 21%, P = 0.0482), and UCP1 (35%, P = 0.0613 and 30%, P = 0.0031) in eAT; 6-month nitrate administration restored these decreased levels to near control values. In addition, nitrate increased adipocyte density by 193% and decreased adipocyte area by 53% in rats with T2D. In conclusion, long-term low-dose nitrate administration increased mRNA and protein expressions of browning genes in white adipose tissue of male rats with T2D; these findings partly explain favorable metabolic effects of nitrate administration in diabetes.


Assuntos
Adipócitos Marrons/efeitos dos fármacos , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/genética , Epididimo/efeitos dos fármacos , Nitratos/administração & dosagem , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos Marrons/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Epididimo/metabolismo , Glucose/metabolismo , Insulina/sangue , Masculino , PPAR gama/genética , PPAR gama/metabolismo , RNA Mensageiro/genética , Ratos , Ratos Wistar , Estreptozocina/farmacologia
5.
Zhonghua Nan Ke Xue ; 26(5): 446-451, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-33354955

RESUMO

Objective: To explore the possible mechanism of Huanshao Capsules (HSC) protecting the reproductive function in rats with ornidazole-induced asthenozoospermia (AZS). METHODS: Forty SD male rats were randomly divided into four groups of equal number, blank control, AZS model control, HSC and L-carnitine (LC) intervention. The AZS model was established in the latter three groups of rats by intragastrical administration of ornidazole at 400 mg/kg/d for 28 days, and meanwhile the animals in the HSC and LC groups were treated by gavage of HSC at 0.31 g/kg/d and LC at 100 mg/kg/d, respectively. Then, all the rats were killed for examination of the LC content, sperm concentration, sperm motility and expression of OCTN2 mRNA in the epididymis and observation of the histopathological changes in the testis tissue. RESULTS: Compared with the AZS model controls, the rats in the HSC and LC groups showed significantly increased LC content (2 880.3 vs 6 366.5 and 6 934.7 mg/L, P < 0.01), sperm concentration (ï¼»34.58 ± 10.25ï¼½ vs ï¼»46.19 ± 14.23ï¼½ and ï¼»42.25 ± 6.11ï¼½ ×106/ml, P < 0.01), sperm motility (ï¼»42.59 ± 7.54ï¼½% vs ï¼»61.34 ± 7.98ï¼½% and ï¼»61.34 ± 7.98ï¼½%, P < 0.01) and expression of OCTN2 mRNA in the epididymis (26.07% vs 27.26% and 27.15%, P < 0.01). The animals of the HSC group exhibited a higher comparability than those of the LC group to the blank controls in the morphology, arrangement and activity of spermatogenic cells. CONCLUSIONS: HSC can protect the reproductive function and improve sperm concentration and motility in the model rats with ornidazole-induced AZS, which may be associated with its abilities of up-regulating the expression of OCTN2 mRNA and increasing the LC content in the epididymis.


Assuntos
Astenozoospermia , Medicamentos de Ervas Chinesas/uso terapêutico , Ornidazol , Animais , Astenozoospermia/induzido quimicamente , Astenozoospermia/tratamento farmacológico , Cápsulas , Carnitina/metabolismo , Epididimo/efeitos dos fármacos , Epididimo/metabolismo , Masculino , Ornidazol/toxicidade , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Membro 5 da Família 22 de Carreadores de Soluto/metabolismo , Contagem de Espermatozoides , Motilidade Espermática , Espermatozoides
6.
Zhonghua Nan Ke Xue ; 26(5): 457-463, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-33354957

RESUMO

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.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Epididimo , Fertilidade/efeitos dos fármacos , Motilidade Espermática , Testículo , Animais , Cápsulas , Epididimo/efeitos dos fármacos , Feminino , Masculino , Camundongos , Gravidez , Distribuição Aleatória , Contagem de Espermatozoides , Espermatozoides , Testículo/efeitos dos fármacos
7.
Life Sci ; 258: 118192, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32781062

RESUMO

The present study was conducted to identify possible health - promoting effects of wogonin (Wog) on testicular dysfunction in rats caused by cadmium. Pre-treatment of cadmium chloride (Cd: 5 mg/kg b.wt.) administered rats with wogonin (10 mg/kg b.wt) resulted in significant improvement in Cd-induced decrease in body and organ (testes and epididymides) weights. Wogonin treatment significantly improved Cd-induced reduction in sperm quality and quantity, steroidogenic gene (SFI, StAR, CYP11A1, 3ß-HSD, CYP17A1 and 17ß-HSD) and protein (SF1, StAR and CYP17A1) expressions and serum testosterone levels. Wogonin treatment provided significant protection to Cd-induced aggression in testicular oxidative (elevated levels of MDA) and anti-oxidative (diminished activities of SOD, CAT and GPx) status. Wog significantly up-regulated mRNA levels of Nrf2, NQO1 and HO-1 and down-regulation of Keap1 in cadmium treated testes. Wogonin administration significantly suppressed Cd-stimulated increase in inflammatory reactions (increase in NF-κB p65 DNA, p-IKKß, TNF-α levels and decrease in IL-10 levels). Wogonin prevented apoptotic damage by enhanced protein distribution of caspase-9, caspase-3, and Bax due to Cd exposure. Furthermore, Wogonin presented significant protection to histo-morphometric changes resulted after Cd administration. Taken together, the findings of this study provided clear evidence of the therapeutic potential of Cd-induced testicular toxicity at least partly due to its antioxidant, anti-inflammatory and anti-apoptotic properties.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Cádmio/toxicidade , Flavanonas/farmacologia , Substâncias Protetoras/farmacologia , Transdução de Sinais , Testículo/patologia , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Ingestão de Líquidos/efeitos dos fármacos , Epididimo/efeitos dos fármacos , Epididimo/patologia , Comportamento Alimentar/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônios/sangue , Inflamação/patologia , Masculino , Oxirredução , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Esteroides/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo
8.
Nanotoxicology ; 14(7): 893-907, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32529924

RESUMO

This study aimed to evaluate the effects of an intratesticular injection of silver nanoparticles (AgNPs) on reproductive parameters and health of rats, and to evaluate the AgNPs biodistribution in order to develop a nanotechnological contraceptive agent for male animals. Treated animals received 220 µL of AgNPs solution (0.46 µg-Ag/ml) in each testicle and were euthanized: seven, 14, 28, and 56 days after injection. A significant decrease (p < 0.05) in the percentage of motile sperm in D7 (8.8%) was observed, comparing to the control (73.3%), D14 (86.0%), D28 (68.2%), and D56 (90.0%) groups. D7 group also presented a decrease (p < 0.05) in the percentage of normal spermatozoa. Additionally, D7 group showed an increase (p < 0.05) in abnormal midpiece and sperm head morphology compared to the Control group. Seminiferous tubules presented all germline cell types and spermatozoa for all groups. However, D7 group did not present spermatozoa in the epididymis, whereas some spermatozoa and cellular debris were visible in D14 and D28 groups. All animals presented hematological parameters, creatinine, and alanine aminotransferase values within the normal limits for Wistar rats. The percentage of silver found in the liver was always higher than in the other organs analyzed. A pioneering mathematical model is proposed, from which the half-life time of silver in the liver (17 days), spleen (23 days), lungs (30 days), and kidneys (35 days) was extracted. In conclusion, some acute and severe toxic effects were observed in sperm cells following intratesticular injection of AgNPs, although these effects were reversible. No adverse effects to general animal health were observed.


Assuntos
Nanopartículas Metálicas/toxicidade , Reprodução/efeitos dos fármacos , Prata/toxicidade , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Alanina Transaminase/metabolismo , Animais , Epididimo/efeitos dos fármacos , Epididimo/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Nanopartículas Metálicas/administração & dosagem , Ratos , Ratos Wistar , Prata/administração & dosagem , Prata/farmacocinética , Espermatozoides/metabolismo , Baço/efeitos dos fármacos , Baço/metabolismo , Testículo/metabolismo , Distribuição Tecidual
9.
Chemosphere ; 256: 127001, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32447106

RESUMO

N, N-Dimethylacetamide is an FDA approved solvent widely used in pharmaceutical industry to facilitate the solubility of lipophilic, high molecular weight drugs with poor water solubility. However, the cytotoxic effects of DMA raises the concern about its use in clinical applications. In the present study, we address the effect of DMA on spermatogenesis. Male Sprague Dawley rats were injected intra-peritoneally for 8 weeks, once a week at a dose of 862 mg/kg. Analysis of reproductive parameters revealed that DMA treated animals exhibit spermatid formation defects within the testis describing the characteristics of oligozoospermia. A subsequent decrease in epididymal sperm concentration along with distortion of sperm morphology was observed. The mitochondrial and microtubule organization in the sperm is considerably modified by DMA. This disrupts the sperm kinetics thus decreasing the total and progressive sperm motility. Finally, DMA treatment resulted in loss of fertility. Our results indicate that exposure to DMA has a negative impact on spermatogenesis and leads to infertility in male rats by inhibiting the post meiotic stages of sperm development. Therefore, the use of DMA in humans must be closely monitored.


Assuntos
Acetamidas/toxicidade , Excipientes/toxicidade , Espermatogênese/efeitos dos fármacos , Animais , Epididimo/efeitos dos fármacos , Fertilidade/efeitos dos fármacos , Humanos , Infertilidade , Masculino , Ratos , Ratos Sprague-Dawley , Reprodução , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos
10.
Ecotoxicol Environ Saf ; 196: 110512, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32244115

RESUMO

Although there are numerous studies on bisphenol A (BPA) on the testis and spermatozoa, the effect of BPA on the physiological link between the testis and maturation of spermatozoa has not been studied. To provide an optimal environment (acidic pH) for sperm maturation in the epididymis, clear cells secrete protons and principal cells reabsorb bicarbonate and the secreted proton. Because of its crucial role in sperm maturation and fertility, functional changes in the epididymis following BPA exposure must be considered to fully understand the mechanisms of BPA on male fertility. Here, we identified the adverse effects of BPA exposure during puberty in male mice. CD-1 male mice were gavaged daily with vehicle (corn oil) and 50 mg BPA/kg-BW for 6 weeks. We determined the changes in epididymis, functional sperm parameters including motility, capacitation status, tyrosine phosphorylation, and fertility-related protein expression and in vitro and in vivo fertility rate following BPA exposure. Expression of vacuolar-type H + -ATPase is necessary for the secretion of protons by clear cells of the caput epididymis and was directly down-regulated following BPA exposure, while there were no changes in the other epithelial cell types in the epididymis. Also, pERK 1/2 signaling pathway was increased significantly in the caput epididymis following BPA exposure. Consequently, the luminal pH slightly increased, resulting in premature capacitation of spermatozoa. Moreover, there was a significant loss of the acrosomal membrane following an increase of protein tyrosine phosphorylation, while PKA activity decreased during sperm capacitation. Fertility-related proteins also showed aberrant expression upon BPA exposure. These modifications resulted in decreased male fertility in vitro and in vivo.


Assuntos
Compostos Benzidrílicos/toxicidade , Poluentes Ambientais/toxicidade , Fertilidade/efeitos dos fármacos , Fenóis/toxicidade , Maturação do Esperma/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Animais , Bicarbonatos/metabolismo , Epididimo/efeitos dos fármacos , Masculino , Camundongos , Fosforilação , Transdução de Sinais , Capacitação Espermática/efeitos dos fármacos , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/metabolismo , Testículo/efeitos dos fármacos
11.
Andrologia ; 52(1): e13454, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31721272

RESUMO

Tramadol is widely abused in Nigeria and has been reported to cause fertility decline via testicular oxidative stress. This study investigated the effect of vitamin E, an antioxidant on some reproductive parameters in male Wistar rats administered tramadol. Twenty male Wistar rats (180-200 g) were randomly assigned into four groups (n = 5) thus: Control (0.2 ml vehicle: olive oil), tramadol-treated (20 mg/kg of tramadol), vitamin E-treated (100 mg/kg of vitamin E) and tramadol + vitamin E-treated (received tramadol and vitamin E) groups. Drugs were administered orally and daily for 28 days. Sperm count, Johnsen's score, germinal epithelial height and serum testosterone, follicle-stimulating hormone (FSH) and luteinising hormone (LH) concentrations were significantly (p < .05) decreased in tramadol-treated and tramadol + vitamin E compared with control and vitamin E-treated groups. Sperm motility, morphology, viability, seminiferous tubular diameter, Leydig cell count, Sertoli cell count and malondialdehyde, superoxide dismutase, glutathione peroxidase and catalase concentrations were not significantly different among the groups. Histology of testis and epididymis in all groups showed no toxicity but decreased sperm population in tramadol-treated and tramadol + vitamin E-treated groups. Tramadol did not cause testicular oxidative stress but impaired testicular function by suppressing testosterone, FSH and LH secretion. Vitamin E administration could not attenuate this impairment in testicular function.


Assuntos
Infertilidade Masculina/tratamento farmacológico , Espermatozoides/efeitos dos fármacos , Transtornos Relacionados ao Uso de Substâncias/complicações , Tramadol/efeitos adversos , Vitamina E/administração & dosagem , Administração Oral , Animais , Modelos Animais de Doenças , Ejaculação/efeitos dos fármacos , Epididimo/efeitos dos fármacos , Epididimo/patologia , Humanos , Infertilidade Masculina/etiologia , Infertilidade Masculina/patologia , Masculino , Nigéria , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/patologia , Testículo/efeitos dos fármacos , Testículo/patologia
12.
Biotech Histochem ; 95(1): 18-26, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31482760

RESUMO

Consumption of fructose-rich food and exposure to endocrine disrupting chemicals continue to increase. High fructose consumption is associated with increased incidence of dyslipidemia, hypertension, hyperuricemia and insulin resistance. Bisphenol A (BPA) is an environmental contaminant that exhibits estrogen-like activity; it impairs reproductive organs, sperm production, spermatogenesis and fertility. We investigated the possible ameliorative effects of melatonin on rat epididymis and sperm characteristics following exposure to fructose and BPA. We used 42 adult male Sprague-Dawley rats divided into seven groups. Group 1, control group, was treated with 25 mg/kg sesame oil + 25 mg/kg 0.1% ethanol. Group 2 was treated with 10% aqueous fructose. Group 3 was treated with 25 mg/kg BPA. Group 4 was treated with 10% fructose and 25 mg/kg BPA. Group 5 was treated with 10% fructose and 20 mg/kg melatonin. Group 6 was treated with 25 mg/kg BPA and 20 mg/kg melatonin. Group 7 was treated with 10% fructose, 25 mg/kg BPA and 20 mg/kg melatonin. After 60 days, epididymal tissue was removed and analyzed using histochemistry and immunohistochemistry. Sperm were counted, and sperm motility and viability were investigated. Administration of BPA caused significant damage to both epididymal tissue and sperm quality; melatonin reduced the damage, but did not prevent it completely.


Assuntos
Compostos Benzidrílicos/farmacologia , Epididimo/efeitos dos fármacos , Frutose/farmacologia , Melatonina/farmacologia , Fenóis/farmacologia , Espermatozoides/efeitos dos fármacos , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Compostos Benzidrílicos/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Claudina-1/genética , Claudina-1/metabolismo , Epididimo/metabolismo , Estrogênios não Esteroides/administração & dosagem , Estrogênios não Esteroides/farmacologia , Frutose/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Melatonina/administração & dosagem , Ocludina/genética , Ocludina/metabolismo , Fenóis/administração & dosagem , Ratos , Ratos Sprague-Dawley , Edulcorantes/administração & dosagem , Edulcorantes/farmacologia , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo
13.
Sci China Life Sci ; 63(1): 116-124, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31102177

RESUMO

Several potential oxidative agents have damaging effects on mammalian reproductive systems. This study was conducted to investigate the effects of glutamate (Glu) and aspartate (Asp) supplementation on antioxidant enzymes and immune defense systems in the outer scrotum of boars injected with H2O2. A total of 24 healthy boars were randomly divided into 4 treatment groups: control (basal diet, saline-treated), H2O2 (basal diet, H2O2-challenged outer scrotum (1 mL kg-1 BW)), Glu (basal diet +2% Glu, H2O2-challenged), and Asp (basal diet+2% Asp, H2O2-challenged). Our results showed that both Glu and Asp supplementation improved testicular morphology and decreased the genital index in the H2O2-treated boars. Glu and Asp administration increased the antioxidant enzyme activities and affected the testicular inflammatory cytokine secretion but had no effect on sex hormone levels. Furthermore, the mRNA expression of CAT, CuZnSOD, and GPx4 was altered in the testes and epididymis of boars treated with Asp and Glu. Glu and Asp supplementation also modulated the expression of TGF-ß1, IL-10, TNF-α, IL-6 and IL-1ß in the testis and epididymis. These results indicate that dietary Glu and Asp supplementation might enhance antioxidant capacity and regulate the secretion and expression of inflammatory cytokines to protect the testes and epididymis of boars against oxidative stress.


Assuntos
Ácido Aspártico/metabolismo , Epididimo/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Testículo/efeitos dos fármacos , Ração Animal , Animais , Antioxidantes/metabolismo , Peso Corporal , Citocinas/metabolismo , Dieta , Epididimo/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Sistema Imunitário/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/metabolismo , Suínos , Testículo/metabolismo
14.
Asian J Androl ; 22(1): 112-117, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31115365

RESUMO

The aim of this work was to study effects of ketotifen fumarate (KF) on prevention of tissue damage in testes of rats with experimental autoimmune orchitis (EAO) and on the contralateral testis in a model of prolonged testicular cord torsion (TCT). Rats with EAO or TCT were injected intraperitoneally once daily with KF or saline solution (vehicle group). Incidence and severity of testicular damage were evaluated by histopathology using an EAO score or a Johnsen score. Mast cells (MC) were identified by histochemistry and quantified. In EAO model, KF significantly reduced severity of histopathological testicular damage compared to rats in the vehicle group. KF also reduced the number of testicular MC compared to vehicle group. Similarly, in TCT model, multifocal damage of the contralateral testis was observed 30 days after testicular torsion characterized by sloughing of the germinal epithelium, seminiferous tubule atrophy, and interstitial edema. Focal signs of inflammation and fibrosis of seminiferous tubular walls were also observed. In contrast, sections of contralateral testis of rats injected with KF and killed 30 days after surgery showed normal histological features. A significant decrease in the number of MC was observed in rats treated with KF compared to untreated animals. In conclusion, we demonstrated that treatment with KF reduced testicular inflammatory process and MC infiltrates in both EAO and TCT models. The results suggest a promising treatment for infertile male patients with testicular pathologies associated with inflammation and germ cell loss.


Assuntos
Doenças Autoimunes/patologia , Epididimite/patologia , Antagonistas dos Receptores Histamínicos H1/farmacologia , Cetotifeno/farmacologia , Mastócitos/efeitos dos fármacos , Orquite/patologia , Torção do Cordão Espermático/patologia , Testículo/efeitos dos fármacos , Animais , Doenças Autoimunes/imunologia , Contagem de Células , Epididimo/efeitos dos fármacos , Epididimo/imunologia , Epididimo/patologia , Epididimite/imunologia , Hipersensibilidade Tardia , Imunidade Celular/efeitos dos fármacos , Masculino , Mastócitos/imunologia , Mastócitos/patologia , Orquite/imunologia , Ratos , Índice de Gravidade de Doença , Torção do Cordão Espermático/imunologia , Testículo/imunologia , Testículo/patologia , Vacinação
15.
Environ Geochem Health ; 42(6): 1715-1724, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31278585

RESUMO

As a new type of nanomaterials, nickel nanoparticles (Ni NPs) have been widely used by human beings, whose exposure probability was greatly increasing. Many studies have shown that Ni NPs can induce apoptosis, oxidative stress and DNA damage. Nowadays, male reproductive health is an important public health problem, which is a hot topic in toxicological research. In the present study, to protect reproductive health, the effect of Ni NPs exposure on spermatogenesis injury was assessed, understanding the toxicity and safety of Ni NPs. Sixty ICR male mice with 20 ± 2 g were randomly divided into five groups. The experimental groups were treated with 5 mg/kg, 15 mg/kg and 45 mg/kg Ni NPs. The reproductive toxicity of Ni NPs on male mice was evaluated by the indexes of testicular organ coefficient, testicular marker enzyme, sperm motility and histopathology. As a result, the somatic index of testis and epididymis increased in each group. Compared with the control group, the activity of testicular markers increased and the sperm motility index decreased in the low-, middle- and high-dose groups. Pathological results indicated that various cell apoptosis and disordered arrangement of cells occurred in the seminiferous tubules of the exposed groups. In conclusion, the findings of this study suggest that Ni NPs have certain damage to spermatogenesis in mice.


Assuntos
Níquel/toxicidade , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Epididimo/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Nanopartículas , Estresse Oxidativo/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/patologia , Testículo/patologia
16.
Environ Toxicol ; 35(2): 268-276, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31696645

RESUMO

Testicular damage is the anomaly that will often accompany diabetes mellitus. Thus, this study aimed to investigate the role that total flavonoids of Epimedium (TFE) played against streptozotocin (STZ)-induced diabetic testicular dysfunction and to elucidate the mechanism of action. The diabetic rat model was induced by vein injection of STZ in healthy rats. Thirty male healthy Spraque-Dawley rats were randomly divided into following groups: the control group, the diabetic group, and the diabetic + TFE group. Gastrointestinal administration begins at fifth week of TFE for 6 weeks. After TFE administration, all animals were euthanized. Testicular tissue samples and blood samples of rats were collected for histopathological examination and for determination of levels of various biomarkers including blood glucose, testosterone, testicular enzymes, and oxidative stress indicators. All testes were weighted to calculate the testicular organ index. Hematoxylin-eosin staining was used for observing the testis and epididymis pathological changes. Protein expression (monocyte chemoattractant protein-1, transforming growth factor-beta-1, interleukin-6, and 3-beta-hydroxysteroid dehydrogenase) was detected by immunohistochemistry and western blot techniques. There was a significant difference in the changes between the diabetes group and the control group. As a result of treat with TFE, the blood glucose decreased but there was no significant difference, and other indicators showed significant improvement. TFE may protect against STZ-induced testicular injury by suppressing inflammation and oxidative stress.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Epimedium/química , Flavonoides/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Biomarcadores/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/imunologia , Epididimo/efeitos dos fármacos , Epididimo/imunologia , Epididimo/patologia , Flavonoides/isolamento & purificação , Inflamação , Masculino , Estresse Oxidativo/imunologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Estreptozocina , Testículo/imunologia , Testículo/patologia
17.
Biomed Res Int ; 2019: 9430964, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781654

RESUMO

The present study was carried out to assess the contraceptive efficacy of sperm agglutinating factor (SAF) isolated from Serratia marcescens, in male Balb/c mice. Mice were administered via an intratesticular route with different concentrations of SAF, viz., 10, 50, 100, 200, or 400 µg, in the right testis only which served as a test while the left side served as control except otherwise stated. Mice were sacrificed on day 3, 7, 14, 21, 30, 45, 60, and 90 after administration, and results in terms of change in body weight, seminal parameters, tissue somatic indices (TSI), hematological parameters, serum level of testosterone, lipid peroxidation, and histology were studied. The body weight and TSI remained unaffected in all the experimental groups. In case of seminal parameters, the right testis treated with 10 µg, 50 µg, 100 µg, 200 µg, or 400 µg of SAF showed azoospermia up to day 7, 14, 21, 45, and 90, respectively. The hematological indices, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were found to be unaltered when the group receiving SAF (test) was compared with the groups receiving phosphate buffer saline (control) in the right testis; however, the treatment had a negative effect on the serum level of testosterone. It also affected the oxidative status of the right testis. Furthermore, histological studies revealed hypospermatogenesis and alterations in the seminiferous tubules which included intraepithelial vacuolation and exfoliation in the right side as compared to the left side. Thus, the results suggest that SAF (400 µg) causes suppression of spermatogenesis, without causing apparent toxic effects.


Assuntos
Anticoncepcionais Masculinos/farmacologia , Serratia marcescens/metabolismo , Aglutinação Espermática/efeitos dos fármacos , Aglutinação Espermática/fisiologia , Espermatozoides/fisiologia , Alanina Transaminase , Animais , Azoospermia , Anticoncepcionais Masculinos/isolamento & purificação , Modelos Animais de Doenças , Epididimo/efeitos dos fármacos , Epididimo/patologia , Rim/patologia , Peroxidação de Lipídeos , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Oligospermia , Túbulos Seminíferos , Baço/patologia , Testículo/efeitos dos fármacos , Testículo/patologia , Testosterona/sangue , Bexiga Urinária/patologia
18.
Toxicol Ind Health ; 35(10): 660-669, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31771500

RESUMO

Arsenic poisoning is well-known for its innumerable toxic and carcinogenic effects. In vivo data on reproductive toxicity are also known but in vitro data are scant. Presently, we evaluated the in vitro toxic effects of sodium arsenite (NaAsO2) on adult mice testes and epididymal tissues using organ cultures. Testicular and epididymal fragments were incubated at 37°C and 33°C, respectively, with 1, 10, 50, and 100 µM concentrations of NaAsO2. Cultures were allowed to incubate for 2 and 24 h. Levels of oxidative stress markers, the reactive oxygen species (ROS) and thiobarbituric acid reactive substance assay (TBARS), antioxidant enzymes, testosterone concentrations, and the extent of sperm DNA damage, were estimated. Results were analyzed statistically at p < 0.05. Results demonstrated both time- and dose-dependent alterations whereby, following 24-h incubation with NaAsO2, substantial increases were noticeable in ROS and TBARS levels and sperm DNA damage (p < 0.001), while decreases (p < 0.001) occurred in catalase, peroxidase, and superoxide dismutase levels at 10, 50, and 100 µM concentrations. Incubations for 2 h revealed similar but relatively less toxic effects. Testosterone concentrations decreased significantly only after 24 h of incubation with 50 (1.95 vs. 2.93 ng g-1; p < 0.01) and 100 µM (1.32 vs. 2.93 ng g-1; p < 0.001) NaAsO2 concentrations. The study concluded that exposure of testicular and epididymal tissue fragments to arsenic under in vitro conditions induces rapid and immediate metabolic and genotoxic damage at higher concentrations.


Assuntos
Arsenitos/farmacologia , Dano ao DNA/efeitos dos fármacos , Epididimo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Compostos de Sódio/farmacologia , Testículo/efeitos dos fármacos , Testosterona/metabolismo , Animais , Relação Dose-Resposta a Droga , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Técnicas de Cultura de Órgãos , Espermatozoides/efeitos dos fármacos
19.
Environ Sci Pollut Res Int ; 26(34): 35253-35265, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31701422

RESUMO

Difenoconazole is a fungicide extensively used in agriculture. The aim of this study was to evaluate the effects of difenoconazole fungicide on the sperm quality of rats. Wistar rats were divided into four groups: control and exposed to 5 (D5), 10 (D10), or 50 mg-1 kg bw-1day (D50) of difenoconazole for 30 days, by gavage. Classical sperm parameters and surface-enhanced Raman scattering (SERS) were performed. Progressive motility, acrosomal integrity, and percentage of morphologically normal spermatozoa were reduced in the D10 and D50 groups in comparison with the control group. Sperm viability was reduced only in the D50 group. Sperm number in the testis and caput/corpus epididymis and daily sperm production were reduced in the three exposed groups. SERS measurements showed changes in the spectra of spermatozoa from D50 group, suggesting DNA damage. In addition, machine learning (ML) methods were used to evaluate the performance of three classification algorithms (artificial neural network-ANN, K-nearest neighbors-K-NN, and support vector machine-SVM) in the identification task of the groups exposed to difenoconazole. The results obtained by ML algorithms were very promising with accuracy ≥ 90% and validated the hypothesis of the exposure to difenoconazole reduces sperm quality. In conclusion, exposure of rats to different doses of the fungicide difenoconazole may impair sperm quality, with a recognizable classification pattern of exposure groups.


Assuntos
Dioxolanos/toxicidade , Fungicidas Industriais/toxicidade , Aprendizado de Máquina , Espermatozoides/efeitos dos fármacos , Triazóis/toxicidade , Animais , Dano ao DNA , Epididimo/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Análise Espectral Raman , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Máquina de Vetores de Suporte , Testículo/efeitos dos fármacos , Testes de Toxicidade
20.
Eur J Pharmacol ; 865: 172774, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31697932

RESUMO

Fluoxetine and sertraline are antidepressants drugs capable to impair male fertility by decreasing the number of sperm cells in the ejaculate. However, the mechanism underlying these effects is still not fully understood. It is also reported that alterations in epididymis contraction induced by different drugs affect the number of sperm cells, leading to male fertility alterations. Therefore, this study aimed to investigate if both fluoxetine and sertraline could affect the rat epididymis contraction, altering the sperm transit and/or sperm count trough rat epididymis. In vitro effects of fluoxetine and sertraline (1, 3 and 10 µM) were evaluated in isolated distal cauda epididymis of rats by pharmacological experiments. The effects of long-term treatment with fluoxetine and sertraline (20 mg/kg, i.p., 21 days) were also checked on distal cauda epididymis contractions, serum testosterone levels, sperm production, sperm reserves and sperm transit time trough rat epididymis. In vitro fluoxetine and sertraline (>3 µM) impaired the contractions induced by KCl, phenylephrine or carbachol although fluoxetine 1 µM potentiate the phenylephrine-induced contractions. Long-term in vivo treatment with fluoxetine and sertraline promoted: (a) an enhancement of rat distal cauda spontaneous contractions; (b) a potentiation of phenylephrine-induced contractions; (c) a decreased in serum testosterone levels; and (d) a diminished daily sperm production, sperm reserves trough epididymis and sperm transit time in rat cauda epididymis. In conclusion, the alteration in the motor activity of epididymis could be associated to the low sperm count in this organ and accelerated transit time trough epididymal cauda of rats.


Assuntos
Antidepressivos/farmacologia , Epididimo/efeitos dos fármacos , Fluoxetina/farmacologia , Sertralina/farmacologia , Espermatozoides/efeitos dos fármacos , Animais , Epididimo/fisiologia , Masculino , Ratos Wistar , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/fisiologia
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