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2.
Life Sci ; 242: 117250, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31899225

RESUMO

BACKGROUND: Endocrine disruptor such as cadmium has been widely reported to cause testicular toxicity, which contributes to recent decline in male fertility worldwide. Glutamine, the most abundant amino acid in the body has been demonstrated to exert protective effects in cellular toxicity. However, its role in testicular toxicity is unknown. The present study is therefore aimed at investigating the effects of glutamine supplementation on cadmium-induced testicular toxicity, and the possible involvement of glucose-6-phosphate dehydrogenase (G6PD) activity. MATERIALS AND METHOD: Male Wistar rats weighing 160-190 g were allotted into 4 groups (n = 5/group): The groups received vehicle (distilled water; p.o.), glutamine (1gkg-1; p.o.), cadmium chloride (5mgkg-1p.o.) and Cadmium chloride plus glutamine respectively, daily for 30 days. Biochemical and histological analyses were performed with appropriate method. RESULTS: Administration of cadmium significantly decreased body weight, sperm count, motility and viability, as well as altered sperm morphology and progressivity. Cadmium also caused atrophy of the seminiferous tubule in addition to disrupted testicular architecture, lumen, Sertoli cells and spermatogonia. Similarly, serum and testicular aspartate transaminase, and malondialdehyde significantly increased, and G6PD, glutathione, nicotinamide adenine dinucleotide phosphate and nitric oxide significantly decreased with corresponding decrease in follicle stimulating hormone, luteinizing hormone and testosterone in cadmium-treated animals compared with control groups. However, supplementation with glutamine attenuated these alterations. CONCLUSION: The present study demonstrates that cadmium induces testicular dysfunction that is attributable to defective G6PD and accompanied by increased lipid peroxidation and impaired NO-dependent endothelial function. Interestingly, glutamine supplementation ameliorates cadmium-induced testicular dysfunction through enhancement of G6PD activity.


Assuntos
Cloreto de Cádmio/toxicidade , Glucosefosfato Desidrogenase/metabolismo , Glutamina/farmacologia , Testículo/efeitos dos fármacos , Animais , Glucosefosfato Desidrogenase/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/ultraestrutura , Testículo/enzimologia
3.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(1): 7-12, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31950782

RESUMO

Objective: To study the effects of genistein (GEN) on reproductive system in prepubertal male rats. Methods: Thirty SPF-rated male SD rats were randomly divided into control group (Con group), low-dose group (G1 group) and high-dose group (G2 group), with 10 rats in each group. Corn oil, 150 mg/kg and 300 mg/kg GEN dissolved in corn oil of equal volume were respectively administered every day and weighed the next day. After 6 weeks, the rats were sacrificed, and the testis, epididymis and prostate were dissected, and organ coefficients were calculated. Histopathological changes of testis was observed. The number of sperm was counted and the rate of sperm malformation was calculated. The concentrations of serum testosterone and estradiol were detected by radioimmunoassay. The protein phosphatase 2, regulatory subunit B, gamma (PPP2R2C) protein expression in testicular tissue was detected by immunofluorescence assay. The mRNA and protein expression levels of PPP2R2C and cyclin dependent protein kinases 2 (CDK2) in rat testis were detected by real-time quantitative fluorescence PCR (RT-qPCR) and Western blot, respectively. The protein phosphatase 2A (PP2A) activity in testicular tissue was detected by immunoprecipitation. Results: There were no statistically significant differences in body mass, sperm number, serum estradiol and PP2A enzyme activity among the groups ( P>0.05). The pathological structure of testicular in G2 group was disordered. Sperm abnormality rate in G1 and G2 groups was higher than that in Con group ( P<0.05). Serum testosterone concentration in G2 group was lower than that in Con group ( P<0.05). The expression of PPP2R2C and CDK2 in G2 group was higher than that in Con group ( P<0.05), but the protein level was lower than that in Con group ( P<0.05). PPP2R2C protein was expressed in testicular tissue in each group. Conclusion: Long-term exposure to high dose (300 mg/kg) GEN during prepuberty may cause adverse effects on reproductive function in adult male rats. Further investigation is needed to determine whether PPP2R2C-PP2A-CDK2 phosphorylation pathway affects reproductive system in rats.


Assuntos
Genisteína , Genitália Masculina , Animais , Estradiol/sangue , Regulação da Expressão Gênica/efeitos dos fármacos , Genisteína/farmacologia , Genitália Masculina/efeitos dos fármacos , Masculino , Fitoestrógenos/farmacologia , Ratos , Ratos Sprague-Dawley , Contagem de Espermatozoides , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/enzimologia , Testosterona/sangue
4.
Toxicol Lett ; 318: 30-43, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31647946

RESUMO

Lead (Pb), a widespread heavy metal, may induce serious diseases, particularly male reproductive injury. However, the mechanisms by which Pb induces testicular injury remain unclear. In this paper, we established a mouse model of Pb-induced testicular injury via an intraperitoneal injection of lead chloride at a concentration of 1.5 mg/kg body weight. We confirmed that Pb could induce a series of injuries, including a low litter size, smaller testes, more weak offspring, direct injury, and aberrant spermiogenesis. Our study demonstrated that Pb could inhibit lysine acetylation (Kac) and succinylation (Ksuc) via western blot (WB) and immunofluorescence (IF) analyses. We subsequently separated different germ cells that contained Pre-meiotic spermatogonia (SPG), meiotic spermatocyte (SPC), and round spermatid (RS) into the Pb-treated and control groups and verified that Pb inhibited Kac in SPC, RS, and particularly, during meiosis. Furthermore, our results regarding the inhibition of pyruvate kinase and mitochondrial electron transport chain complex I and II in the Pb-treated groups suggested that Pb may restrain key enzymes to block the TCA cycle and that the low TCA cycle activity could reduce the contents of two important metabolites, acetyl-CoA and succinyl-CoA, to inhibit Kac and Ksuc. Moreover, we examined the influences of the inhibition of Kac and Ksuc on spermiogenesis, which indicated that decreased Kac and Ksuc could impede the replacement of transition proteins in elongating sperm and disorder the distribution of germ cells in the seminiferous tubule. Our research provides novel insights into the mechanisms of Pb reproductive toxicity with respect to lysine acetylation and succinylation.


Assuntos
Chumbo/toxicidade , Lisina/metabolismo , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Acetilação , Animais , Metabolismo Energético/efeitos dos fármacos , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/patologia , Testículo/metabolismo , Testículo/patologia
5.
Sci Total Environ ; 702: 134775, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31710847

RESUMO

Butylated hydroxyanisole (BHA), a synthetic phenolic antioxidant (SPA), has been used as a food additive. However, BHA acts as an environmental hormone, i.e., endocrine disruptor. Here, we investigated BHA-induced male reproductive dysfunction in mouse Leydig and Sertoli cells. We found that BHA suppressed proliferation and induced cell cycle arrest in TM3 and TM4 cells. Furthermore, we investigated mitochondrial permeabilization, expression profiles of pro-apoptotic and anti-apoptotic proteins, calcium influx, and endoplasmic reticulum (ER) stress in testicular cells after BHA treatment. The results indicated that BHA-mediated calcium dysregulation and ER stress downregulated steroidogenesis- and spermatogenesis-related genes in mouse testis cell lines. Additionally, proliferation of both TM3 and TM4 cells in response to BHA treatment was regulated via the Mapk and Akt signaling pathways. Therefore, constant BHA exposure may lead to testicular toxicity via mitochondrial dysfunction, ER stress, and abnormal calcium levels in the testis.


Assuntos
Hidroxianisol Butilado/toxicidade , Estresse do Retículo Endoplasmático/fisiologia , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Cálcio/metabolismo , Homeostase/efeitos dos fármacos , Masculino , Camundongos
6.
Ecotoxicol Environ Saf ; 187: 109824, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31654863

RESUMO

Microcystin-LR (MC-LR), a widespread environmental contaminant, has been shown to have potent acute testicular toxicity. However, magnitudes of toxic effects, induced by MCs, depend on route and magnitude of exposure to the toxin. In the present study, male mice were orally exposed 1, 10 or 100 µg/L MC-LR for 90 or 180 days, and pathological approach and the isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics were employed with testes. Proteomics revealed that a number of differentially altered proteins may be involved in MC-LR-induced chronic testicular toxicity. The biological process analysis indicated the altered proteins played an important role in biological adhesion, cellular process, response to stimulus or rhythmic process. The cellular component analysis revealed that most of the proteins with altered expression associated with cell part, extracellular region, extracellular region part, membrane, membrane part, organelle or organelle part. The molecular function showed that these proteins were critical in molecular transducer activity. Integrity analyses provide first compelling evidence that MC-LR significantly cause dysfunction of blood-testis barrier (BTB) through affecting tight junctions and gap junctions. Moreover, phosphatidylinositol 3-kinase (PI3K)/AKT eventually contributed to injury result from chronic low-level MC-LR treatment. Identification of proteins in testis responsive to MC-LR provides insights into molecular mechanisms of chronic toxicity of MCs.


Assuntos
Poluentes Ambientais/toxicidade , Microcistinas/toxicidade , Proteoma/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Barreira Hematotesticular/efeitos dos fármacos , Barreira Hematotesticular/fisiopatologia , Masculino , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Proteômica , Transdução de Sinais/efeitos dos fármacos , Testículo/metabolismo
7.
Sci Total Environ ; 701: 135077, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31733399

RESUMO

Aflatoxin B1 (AFB1) is an unavoidable environmental pollutants, which seriously endangers human and animal health. AFB1 has male reproductive toxicity, yet the underlying mechanisms remain inconclusive. Mitochondra are a kind of crucial organelle for maintaining spermatogenesis in testis. Thus, we hypothesized that AFB1 can impair mitochondria to aggravate testicular damage and spermatogenesis disorder. To verify this hypothesis, 48 male mice were intragastrically administered with 0, 0.375, 0.75 or 1.5 mg/kg body weight AFB1 for 30 days, respectively. In this study, we found AFB1 caused testicular histopathological lesions and spermatogenesis abnormalities, with the elevation of oxidative stress (increased H2O2, whereas decreased SOD and GSH). Significant mitochondria structure damage of germ cells and Leydig cells, MMP loss, ATP contents reduction, and inhibited activities of mitochondrial complexes I-IV in mice testis were found in AFB1 treatment groups. Besides, AFB1 inhibited mitochondrial biogenesis and mitochondrial dynamics, presenting as the decreased mRNA and protein expressions of PGC-1α, Nrf1, Tfam, Drp1, Fis1, Mfn1 and Opa1. The results revealed that the mitochondrial damage were involved in AFB1-induced testicular damage and spermatogenesis disorder, providing a considerable direction to clarify potential mechanisms of AFB1 reproductive toxicity.


Assuntos
Aflatoxina B1/toxicidade , Mitocôndrias/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Masculino , Camundongos , Espermatogênese/efeitos dos fármacos , Testes de Toxicidade
8.
Chemosphere ; 240: 124900, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31563099

RESUMO

Spirotetramat (SPT) is a new tetronic acid derivative insecticide used to control scales and aphids; the potential for endocrine disruptor effects in fish could not be finalized with the available data. In this study, zebrafish were selected to assess the endocrine-disrupting effects. Significant decrease of plasma estradiol (E2), testosterone (T) and 11-ketotestosterone (11-KT) were observed in both male and female following the spirotetramat exposure; the vitellogenin (VTG) level in females significantly decreased. The expression of the hypothalamic-pituitary-gonad (HPG) axis genes fshr, lhr and esr1 showed significant increase in the gonads, which expression in males is higher than in females. In addition, the activities of capspase-3 and caspase-9 significantly decreased in both males and females liver, while the capspase-3 and caspase-9 were increased in male testis, the mRNA expression levels of genes expression related to the apoptosis pathway were also significantly altered after the spirotetramat exposure. Additionally, we found the parental zebrafish exposed to spirotetramat induced the development delay of its offspring. Above all, the adverse effects induced by spirotetramat suggesting that spirotetramat is a potential exogenous hazardous agent.


Assuntos
Compostos Aza/toxicidade , Inseticidas/toxicidade , Compostos de Espiro/toxicidade , Animais , Apoptose , Disruptores Endócrinos/toxicidade , Estradiol/metabolismo , Estrogênios/farmacologia , Feminino , Expressão Gênica , Gônadas/efeitos dos fármacos , Fígado/metabolismo , Masculino , Testículo/efeitos dos fármacos , Testosterona/análogos & derivados , Vitelogeninas/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo
9.
BMC Complement Altern Med ; 19(1): 367, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31830971

RESUMO

BACKGROUND: ChondroT, a new herbal medication, consists of Angelica grosseserrata Maxim., Lonicera japonica Thunb., Angelica gigas Nakai, Clematis terniflora var. manshurica (Rupr.) Ohwi, and Phellodendron amurense Rupr. (6:4:4:4:3). Our previous studies have shown that ChondroT exhibits significant anti-arthritic and anti-inflammatory effects. In this study, we aimed to assess the toxicological safety assessment of ChondroT. METHODS: This study was designed to assess the safety of ChondroT after repeated oral administration. Male and female Sprague-Dawley rats were treated with ChondroT at oral doses of 0, 500, 1000, and 2000 mg/kg for 13 weeks. Mortality, clinical signs, body weight changes, food consumption, ophthalmological findings, urinalysis, hematological and blood-chemical parameters, necropsy findings, organ weights, and histological markers were recorded throughout the study period. Rats were also monitored for an additional 4 weeks to determine the recovery time. RESULTS: No death occurred and no significant changes in food consumption, ophthalmologic findings, and urinalysis were found. Although there were alterations in clinical signs, body weights, hematological parameters, blood-chemical parameters, necropsy findings, organ weights, and histological markers, they were not considered to be toxicologically significant. CONCLUSIONS: The results suggest that the no-observed adverse effects level (NOAEL) was 2000 mg/kg/day for the test substance. ChondroT, a new complex herbal medication composed of five plants, can therefore be used safely at the NOAEL.


Assuntos
Extratos Vegetais/toxicidade , Testes de Toxicidade Subcrônica , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Feminino , Masculino , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Próstata/efeitos dos fármacos , Próstata/patologia , Ratos , Ratos Sprague-Dawley , Glândula Submandibular/efeitos dos fármacos , Glândula Submandibular/patologia , Testículo/efeitos dos fármacos , Testículo/patologia
10.
BMC Complement Altern Med ; 19(1): 333, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771569

RESUMO

BACKGROUND: Monotropein, astragalin, and spiraeoside (MAS) are active compounds extracted from medicinal herbs; monotropein from Morinda officinalis How (Rubiaceae), astragalin (kaempferol 3-O-glucoside) from Cuscuta chinensis Lamark (Convolvulaceae) and spiraeoside from the outer scales of Allium cepa L. (Liliceae) in a ratio of 6.69:0.41:3.61. Monotropein, astragalin, and spiraeoside are well-known antioxidants, anti-inflammatory, and antinociceptive agents. The current investigation aims to study the molecular mechanism of varicocele-induced male infertility and the underlying pharmacological mechanisms of MAS. METHODS: Four groups were included: control (CTR), MAS 200 group (MAS 200 mg/kg), varicocele group (VC), and VC + MAS 200 group (MAS 200 mg/kg). Sprague-Dawley (SD) rats were treated with 200 mg/kg MAS or vehicle once daily for 28 days. The possible signaling mechanism and effects of MAS were measured via histological staining, immunohistochemistry, western blot, and biochemical assays. RESULTS: Parameters such as sperm motility and count, Johnsen's scores, spermatogenic cell density, serum testosterone, testicular superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and expression of the steroidogenic acute regulatory protein (StAR) improved significantly in the VC + MAS 200 group compared with the VC group. MAS treatment of varicocele-induced group significantly decreased the levels of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as testicular interleukin-6 (IL6), tumor necrosis factor-α (TNF-α), ROS/RNS, and malondialdehyde (MDA). It also decreased the apoptotic index and reduced the expression of endoplasmic reticulum (ER) protein levels (Grp78, p-IRE1α, and p-JNK) and apoptotic markers such as cleaved caspase-3 and Bax/Bcl2 ratio. CONCLUSION: This study suggests that the crosstalk between oxidative stress, ER stress, and mitochondrial pathway mediates varicocele-induced testicular germ cell apoptosis. MAS promotes spermatogenesis in varicocele-induced SD rat, probably by decreasing cytokines (IL-6, TNF-α) levels, regulating abnormal sex hormones, and decreasing oxidative stress, ER stress, and apoptosis.


Assuntos
Iridoides/farmacologia , Quempferóis/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Quercetina/análogos & derivados , Varicocele/metabolismo , Animais , Antioxidantes/farmacologia , Peso Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Masculino , Mitocôndrias/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Quercetina/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Testículo/química , Testículo/efeitos dos fármacos , Testículo/patologia , Varicocele/patologia
11.
Environ Health Prev Med ; 24(1): 62, 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31759394

RESUMO

BACKGROUND: Mercury has been documented as an industrial risk that posed a serious danger to human health. Mercury exposure results in oxidative stress that may lead to the pathogenesis of male reproductive dysfunction. The present study investigated the ameliorating potential of Chenopodium album L. and vitamin C against mercuric chloride-induced oxidative deterioration of reproductive functions in adult male rats. METHODS: Group 1 (control) received saline. Group 2 received Mercury (0.15 mg/kg b.w, i.p) dissolved in distilled water. Groups 3 and 4 were given oral gavage of vitamin C (200 mg/kg b.w) and the ethanolic extract of C. album (200 mg/kg b.w) respectively, along with Mercury (0.15 mg/kg b.w, i.p). Group 5 was treated only with C. album (200 mg/kg b.w). After 30 days of the treatment, the rats were dissected and their testicular tissue and the cauda epididymis were used for biochemical analysis while blood plasma was used for protein determination. RESULTS: The applied dose-treatment of Mercury-induced oxidative stress in the testis and cauda epididymis tissues of the rats was apparent by a noteworthy decrease in total protein, CAT, SOD, POD, and GST values while there was increase in ROS and TBARS levels. Furthermore, Mercury decreases daily sperm production and enhanced sperm DNA damage as noticeable by an increase in the head and tail length of comets and decrease in intact DNA. There was no significant effect on the body weight and the weight of the reproductive tissues. Treatment with C. album significantly ameliorated the total protein, ROS, and TBARS content. Similarly, the level of CAT, SOD, POD, and GST was significantly improved and the daily sperm production was significantly increased. Furthermore, C. album administration significantly protected Mercury-induced sperm DNA damage. The results of the extract treatment group were compared with those of vitamin C in detoxifying the oxidative stress and restoring the sperm parameters. CONCLUSION: C. album showed protection against Mercury-induced oxidative stress by ameliorating antioxidant enzyme activity, daily sperm production, and DNA damage in rat testes. This suggests that C. album could be beneficial against toxicity induced by an environmental toxicant.


Assuntos
Ácido Ascórbico/uso terapêutico , Chenopodium album/química , Cloreto de Mercúrio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Testículo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Ácido Ascórbico/administração & dosagem , Dano ao DNA/efeitos dos fármacos , Quimioterapia Combinada , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Espermatogênese/efeitos dos fármacos , Testículo/metabolismo , Testículo/fisiologia , Resultado do Tratamento
12.
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
13.
J Agric Food Chem ; 67(48): 13333-13343, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31703480

RESUMO

Fluoride (F) widely exists in the water and food. Recent studies reported that F induced testicular toxicity via inflammation reaction. This study was aimed to explore the mechanism of F-induced inflammation in testis. 100 healthy male mice (BALB/cJ strain) were randomly divided into five groups including: control, experimental autoimmune orchitis (EAO), and three F groups (25, 50, and 100 mg/L sodium fluoride (NaF)). After 150 d, the results showed a significant increase in testicular cytokines levels including of IL-17A, IL-6, IFN-γ, and TNF-α in NaF and EAO groups compared with control group. Interestingly, the presence of specific antisperm autoantibodies in antitesticular autoantibodies and the notable recruitment of immunocyte (T cells and dendritic cells) were also observed in NaF and EAO groups. In addition, findings showed that in NaF and EAO groups macrophages and T cells both significantly secreted IL-17A, and the protein and mRNA levels of cytokines (IL-6 and TGF-ß) were significantly increased. From these results, it can be concluded that autoimmune orchitis and IL-17A are implicated in F-induced testicular inflammation.


Assuntos
Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/imunologia , Fluoretos/efeitos adversos , Interleucina-17/imunologia , Orquite/imunologia , Testículo/imunologia , Animais , Doenças Autoimunes/genética , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Humanos , Interleucina-17/genética , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Orquite/induzido quimicamente , Orquite/genética , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Testículo/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
14.
Eur. j. anat ; 23(6): 393-403, nov. 2019. graf, ilus, tab
Artigo em Inglês | IBECS | ID: ibc-185082

RESUMO

Hepatitis C is a widely distributed problem all over the world, especially Egypt. Chronically infected people develop serious liver disease and now it is the most common cause for liver transplantation. Recently, a new regimen, sofosbuvir (sovaldi), alone or with combinations as sovaldi-ribavirin, was approved for treating this disease. There are limited studies that explore the effects of these drugs on the reproductive organs, and hence affection of male fertility while using these drugs. This study aims to throw more light on whether sovaldi or sovaldi-ribavirin causes testicular damaging effects in the adult male albino rats. We investigated the effect of this regimen in a dose equivalent to that used in the human (41 mg/kg once daily orally for sovaldi and 41 mg/kg twice daily orally for ribavirin) for consecutive 5 and 10 days. There was highly significant decrease in testosterone hormone level and marked degenerative changes in the seminiferous tubules and the testicular interstitium, with increase in collagen deposits in sovaldi treated rats, and in a more extensive manner in sovaldi-ribavirin treated rats. There was a significant increase of deoxyribonucleic acid (DNA) fragmentation in the treated groups after 10 days. However, there was a non-significant difference in DNA fragmentation in the treated groups after 5 days when compared with control. Immuno-histochemistry detection of caspase-3 showed significant increase in its expression in the treated groups after either 5 or 10 days. This denoted the specificity of caspase-3 immunohistochemistry technique in the detection of early apoptotic changes. It was concluded that sovaldi and sovaldi ribavirin induced gonado toxic effects through induction of DNA fragmentation via up regulation of caspase-3, and that the resulting damaging effects increased with longer duration of drug in take


No disponible


Assuntos
Animais , Ratos , Sofosbuvir/administração & dosagem , Hepatite C/induzido quimicamente , Hepatite C/veterinária , Testículo/efeitos dos fármacos , Ribavirina/administração & dosagem , Disruptores Endócrinos/administração & dosagem , Sofosbuvir/toxicidade , Imuno-Histoquímica , Projetos de Pesquisa , Eletroforese/métodos
15.
J Cancer Res Clin Oncol ; 145(12): 3037-3045, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31646373

RESUMO

INTRODUCTION: Because spermatocytic tumors of the testis are rare, only limited evidence exists regarding the malignant potential and the optimal management of localized and metastatic disease. MATERIALS AND METHODS: We performed a systematic review through MEDLINE, EMBASE, Scopus, Cochrane Database of Systematic Reviews and Web of Science to identify reports including patients with testicular spermatocytic tumors. RESULTS: From originally 7863 studies, we extracted data of 146 patients of which 99% were treated with radical orchiectomy. Metastases in patients with initially localised disease were diagnosed in 7% of patients and detected after a median follow-up of 5.5 months (range 2-21 months). Patients with aggressive histology (sarcoma or anaplastic subtype) were more likely to have metastatic disease (6/124 (5%) vs 9/22 (41%), p < 0.001). Patients with metastatic disease had larger primary tumors (92.5 vs 67.5 mm, p = 0.05). Life expectancy in patients with metastatic disease ranged from 1 to 25 months. CONCLUSION: The published literature does neither support the use of testis sparing surgery nor adjuvant therapy. Patients with aggressive variants or larger tumors were more likely to have metastases and develop recurrences within the first few years. Patients with metastatic disease have a limited life expectancy and metastatic spermatocytic tumors are not as responsive to chemotherapy as germ cell cancers.


Assuntos
Metástase Neoplásica/tratamento farmacológico , Espermatócitos/efeitos dos fármacos , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/cirurgia , Testículo/efeitos dos fármacos , Testículo/cirurgia , Humanos , Masculino , Neoplasias Primárias Múltiplas/tratamento farmacológico , Neoplasias Primárias Múltiplas/cirurgia , Resultado do Tratamento
16.
Environ Sci Pollut Res Int ; 26(33): 34575-34583, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31650475

RESUMO

The aim of the present study was to investigate whether curcumin (CUR) can ameliorate cadmium-induced reproductive toxicity and its mechanism. A total of 48 male mice were equally divided into 4 groups: control, CdCl2 (2 mg/kg, intraperitoneally inject) curcumin (50 mg/kg, intraperitoneally inject), co-treatment with curcumin (50 mg/kg), and CdCl2 (2 mg/kg) for 10 days. The results demonstrated that CdCl2 reduces sperm motility, decreases the sperm density and serum testosterone content, and significantly improves the rate of sperm deformity. CdCl2 increased the level of testicular total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px) activity, and glutathione (GSH), and CdCl2 declined the level of malondialdehyde (MDA). However, the semen quality of the mice in the curcumin intervention group was improved. Moreover, the testosterone content and antioxidant capacity were increased. In the Cd group mice, the expression of testicular Nrf2, as well as the mRNA and protein expressions of the downstream target molecules, glutathione peroxidase (GSH-Px), and γ-glutamylcysteine synthetase (γ-GCS) of Nrf2 declined, while the above genetic expressions elevated significantly in the curcumin intervention group. Our results suggested that curcumin could protect against Cd-induced testicular injury via activating the Nrf2/ARE signaling pathway.


Assuntos
Antioxidantes/farmacologia , Cádmio/toxicidade , Curcumina/farmacologia , Testículo/fisiologia , Animais , Antioxidantes/metabolismo , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Análise do Sêmen , Transdução de Sinais/efeitos dos fármacos , Motilidade Espermática/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testosterona/metabolismo
17.
Int Braz J Urol ; 45(5): 1043-1054, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31626524

RESUMO

OBJECTIVE: Anacyclus Pyrethrum (AP) and Tribulus Terrestris (TT) have been reported as male infertility treatment in several studies; however, in Iranian traditional medicine these two plants are prescribed simultaneously. In this study, we aimed to determine the effects of AP and TT extracts both separately and simultaneously on the male Wistar rat fertility parameters. MATERIALS AND METHODS: 32 male Wistar rats were divided into 4 groups: Control, TT, AP, and AT treated groups. Treatment continued for 25 days and rats were weighed daily. Their testes were dissected for histological studies. Sperm analysis including sperm count, viability and motility were performed. Serum was obtained to evaluate testosterone, LH and FSH levels. Histological studies were conducted to study Leydig, and Sertoli cells, spermatogonia and spermatid cell numbers, and to measure seminiferous diameter and epithelium thickness. RESULTS: Sperm count increased in all the treatment groups. Sperm viability and motility in AT and AP groups were elevated. TT and AT groups showed signifi cantly increased testosterone level compared to control group (P=004, P=0.000, respectively) and TT, AP and AT treatment groups showed increased LH level (P=0.002, P=0.03 and P=0.000, respectively) compared to control, while only AT group showed increased FSH (p=0.006) compared to control. Histological studies showed signifi cant increase of spermatogonia, Leydig and Sertoli cell numbers and epithelial thickness in AT group compared to other groups. All the treatment groups had higher number of Leydig, spermatogonia and spermatid cells. CONCLUSION: TT and AP improved sexual parameters; however, their simultaneous administration had higher improving effects on studied parameters.


Assuntos
Chrysanthemum cinerariifolium/química , Infertilidade Masculina/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Tribulus/química , Animais , Peso Corporal , Fertilidade/efeitos dos fármacos , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Masculino , Tamanho do Órgão , Extratos Vegetais/farmacologia , Ratos Wistar , Valores de Referência , Reprodutibilidade dos Testes , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testosterona/sangue , Resultado do Tratamento
18.
Ecotoxicol Environ Saf ; 186: 109697, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31629905

RESUMO

Although the acute and/or chronic exposure to AFB1 has been widely investigated, the study on the toxic effects resulted from the subchronic exposure of AFB1 which is more close to the real scenario in view of the regional and seasonal characters of aflatoxin-producing strains is still limited. To understand the subchronically toxic effects of AFB1, we studied the AFB1-induced oxidative damage, reproductive impairment as well as their potential correlations and mechanisms at the molecular level. Generally, our results showed that subchronic exposure of AFB1 gave rise to pathological and oxidative damages in mice, disrupted oxidation-reduction homeostasis, activated mitochondrial apoptotic and p53-regulated signaling pathways, induced DNA and chromosomal damages and increased the rate of sperm malformation. Importantly, reproductive toxic effects were detected in AFB1-treated mice under a subchronic exposure, which was evidenced by the ascended sperm malformation. Based on our pilot study, it's speculated that the partial mechanism of reproductive toxicity may be the oxidative damages, especially DNA damages directly induced by AFB1. In short, our study demonstrated that severe damages can be caused even by a subchronic exposure as well as hinted that reproductive toxicity also should be taken into consideration when conducting risk assessments of the subchronic exposure of AFB1.


Assuntos
Aflatoxina B1/toxicidade , Dano ao DNA/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Masculino , Camundongos , Oxirredução , Testículo/efeitos dos fármacos , Testes de Toxicidade Subcrônica
19.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3406-3414, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602902

RESUMO

This paper summarizes the research progress of reproductive toxicity of Tripterygium wilfordii from 1979,and the toxicity characterization,damage mechanism,and attenuated measures are summarized. It was found that,the reproductive toxicity caused by T. wilfordii is mainly distributed on components of Tripterygium glycosides,triptolide,tripchlorolide,and clinically preparations,such as Leigongteng Tablets and Tripterygium Glycosides Tablets. Adverse reactions to male reproductive system caused by Tripterygium preparations mainly include decreased sperm motility,oligospermia or spermatozoa,decreased fertility or infertility,etc. Long-term drug use may also lead to testicular atrophy and decreased sexual desire. Adverse reactions to women are mainly manifested as menstrual disorders,decreased menstrual volume or even amenorrhea,decreased sexual desire,infertility,etc. The reproductive toxicity of T. wilfordii is related to apoptosis of reproductive cells,disturbance of spermatogenesis or oogenesis,damage of testis and ovary in reproductive target tissues,and changes of internal environment in gonad tissues( hormones,hormone synthesis rate-limiting enzymes and energy metabolism). Drug compatibility,hormone replacement,medication duration and dosage form changes can help reduce the damage of T. wilfordii to the reproductive system. In addition,in view of the existing problems in the current study,the author proposes new directions in clinical studies,pharmacological metabolism mechanism,preparation quality standards and new therapeutic effects,etc.,to provide a basis for the safe and reasonable clinical application of T. wilfordii.


Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Genitália/efeitos dos fármacos , Tripterygium/toxicidade , Feminino , Humanos , Masculino , Ovário/efeitos dos fármacos , Testículo/efeitos dos fármacos
20.
Environ Pollut ; 255(Pt 2): 113316, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31610511

RESUMO

Paraquat is a fast and non-selective herbicide that is widely used in crop cultivation and conservation tillage systems. Animal experiments have shown that paraquat decreases sperm quality and testicular organ coefficient, but its effects on the development of Leydig cells remain unclear. The objective of the current study was to investigate the effects of paraquat exposure on the Leydig cell development in rats during puberty. Twenty-eight male 35-day-old Sprague-Dawley rats were divided into 4 groups: 0, 0.5, 2.0, and 8 mg kg-1 d-1 paraquat. Paraquat was gavaged for 10 d. Adult Leydig cells were isolated and treated with paraquat for 24 h. Paraquat in vivo significantly decreased body and testis weights at 8 mg kg-1 and lowered serum testosterone levels at 2 and 8 mg kg-1 without affecting the levels of serum luteinizing hormone and follicle-stimulating hormone. Paraquat did not alter Leydig cell number and PCNA labeling index. Real-time PCR showed that paraquat down-regulated the expression of Lhcgr, Scarb1, Cyp11a1, Cyp17a1, and Hsd17b3 genes and their proteins at 2 or 8 mg kg-1, while it up-regulated the expression of Srd5a1 at 8 mg kg-1. Paraquat increased ROS and decreased testosterone production by Leydig cells at 1 and 10 µM after in vitro 24-h exposure. Vitamin E (40 µg/ml) reversed paraquat-induced ROS and suppression of testosterone synthesis in vitro. In conclusion, paraquat directly delays Leydig cell differentiation to block testosterone synthesis via down-regulating the expression of critical testosterone synthesis-related genes and up-regulating the expression of testosterone metabolic enzyme (Srd5a1) gene and possibly via increasing ROS production.


Assuntos
Herbicidas/toxicidade , Células Intersticiais do Testículo/efeitos dos fármacos , Paraquat/toxicidade , Animais , Diferenciação Celular/efeitos dos fármacos , Regulação para Baixo , Hormônio Foliculoestimulante/sangue , Herbicidas/metabolismo , Hormônio Luteinizante/sangue , Masculino , Ratos , Ratos Sprague-Dawley , Maturidade Sexual , Esteroide 17-alfa-Hidroxilase/metabolismo , Testículo/efeitos dos fármacos , Testosterona/sangue , Regulação para Cima
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