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1.
Chemosphere ; 242: 125286, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31896186

RESUMO

Bisphenol-B (BPB), an analogue of bisphenol-A is used in the plastic industry. It has been found to leach from plastic containers leading to its contamination in canned food products. Moreover, it has also been detected in human samples such as sera and urine. BPB is recognized as a potential endocrine disrupting chemical owing to its estrogenic and anti-androgenic nature. Therefore, it was pertinent to study the effect of BPB exposure during the adolescence age (5-6 weeks old) in male mice. Weekly intraperitoneal injections of 5, 10 and 15% LD50 of BPB were given for 2 weeks to acute exposure groups and for 4 weeks to sub-acute exposure groups. BPB exposure induces change in enzymatic and non-enzymatic oxidative stress markers in sperm samples. DNA damage was also observed in sperm cells on acute and sub-acute exposures. Furthermore, BPB exposure led to a marked decline in sperm count and compromised sperm morphology. Computer assisted sperm analysis (CASA) revealed a significant decrease in sperm quality and progressive motility. Thus, both the acute and sub-acute exposures of adolescent male mice to BPB adversely affect the sperms' quality, functions and morphology.


Assuntos
Compostos Benzidrílicos/toxicidade , Dano ao DNA , Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Fenóis/toxicidade , Espermatozoides/efeitos dos fármacos , Fatores Etários , Animais , Humanos , Masculino , Camundongos , Oxirredução , Contagem de Espermatozoides , Espermatozoides/patologia , Testes de Toxicidade Aguda , Testes de Toxicidade Subaguda
2.
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
3.
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
4.
Chem Biol Interact ; 315: 108869, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31682803

RESUMO

Spermatogenic dysfunction is one of the major secondary complications of male diabetes. Salidroside (SAL) is the important active ingredients isolated from Herba Cistanche, which exhibits numerous pharmacological activities such as antioxidant, anti-diabetic, and anti-inflammatory effects. The present study was designed to determine whether SAL contributes to the recovery from spermatogenic dysfunction in streptozotocin (STZ) induced type-1 diabetic mice. SAL (25, 50, or 100 mg/kg) and Clomiphene citrate (CC, 5 mg/kg) were orally administered to male type-1 diabetic mice for 10 weeks. Testis tissues were collected for histopathological and biochemical analysis. Moreover, reproductive organ weight, sperm parameters, and testicular cell DNA damage were estimated. The results revealed that SAL significantly improved the weight of the reproductive organs, sperm parameters and testicular morphology to different degrees in type-1 diabetic mice. Furthermore, reactive oxygen species (ROS) and malondialdehyde (MDA) levels were significantly reduced, and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), markedly increased in the testicular tissue after SAL treatment. In addition, our data also showed a marked downregulation the fluorescence expressions of p38 MAPK phosphorylation and upregulation the protein expressions of ZO-1, Occludin, Claudin-11 and N-cadherin after SAL administration (100 mg/kg) compared with the type-1 diabetic group. In conclusion, these results demonstrated that SAL exerts protective effects on type-1 diabetes-induced male spermatogenic dysfunction, which is likely mediated by inhibiting oxidative stress-mediated blood testis barrier damage.


Assuntos
Barreira Hematotesticular/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glucosídeos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fenóis/farmacologia , Substâncias Protetoras/farmacologia , Espermatogênese/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Barreira Hematotesticular/metabolismo , Catalase/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/metabolismo , Glutationa/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Contagem de Espermatozoides/métodos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Estreptozocina/farmacologia , Superóxido Dismutase/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo
5.
Zoo Biol ; 39(1): 23-28, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31617256

RESUMO

The objective of this study was to investigate variation in sperm quality metrics (motility, velocity, and concentration) in the critically endangered Mississippi gopher frog (Lithobates sevosus) over three sampling time points after a luteinizing hormone-releasing hormone analog (LHRHa) induction injection. Sperm was repeatedly collected from 11 individuals over three sampling times (30, 60, and 120 min) after injection. Variation in sperm quality was investigated using a repeated-measures mixed model approach. Repeated measures analyses of variance showed a significant effect of sampling time for percent motility and velocity. Concentration was found to be marginally related to sampling time, while progressive motility was not significantly related to time after injection. Our findings are important for optimizing assisted reproduction-related fertilization success and increasing the successful propagation of endangered species of imperiled frogs in captive breeding programs.


Assuntos
Hormônio Liberador de Gonadotropina/farmacologia , Ranidae/fisiologia , Espermatozoides/efeitos dos fármacos , Animais , Espécies em Perigo de Extinção , Hormônio Liberador de Gonadotropina/administração & dosagem , Masculino , Espermatozoides/fisiologia
6.
Cell Mol Life Sci ; 77(1): 93-113, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31377843

RESUMO

Infertility is a global health problem involving about 15% of couples. Approximately half of the infertility cases are related to male factors. The oxidative stress, which refers to an imbalance in levels of reactive oxygen species (ROS) and antioxidants, is one of the main causes of infertility in men. A small amount of ROS is necessary for the physiological function of sperm including the capacitation, hyperactivation and acrosomal reaction. However, high levels of ROS can cause infertility through not only by lipid peroxidation or DNA damage but inactivation of enzymes and oxidation of proteins in spermatozoa. Oxidative stress (OS) is mainly caused by factors associated with lifestyle. Besides, immature spermatozoa, inflammatory factors, genetic mutations and altering levels of sex hormones are other main source of ROS. Since OS occurs due to the lack of antioxidants and its side effects in semen, lifestyle changes and antioxidant regimens can be helpful therapeutic approaches to overcome this problem. The present study aimed to describe physiological ROS production, roles of genetic and epigenetic factors on the OS and male infertility with various mechanisms such as lipid peroxidation, DNA damage, and disorder of male hormone profile, inflammation, and varicocele. Finally, the roles of oral antioxidants and herbs were explained in coping with OS in male infertility.


Assuntos
Antioxidantes/uso terapêutico , Infertilidade Masculina/tratamento farmacológico , Infertilidade Masculina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Gerenciamento Clínico , Humanos , Infertilidade Masculina/fisiopatologia , Masculino , Espécies Reativas de Oxigênio/metabolismo , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/patologia
7.
Environ Pollut ; 256: 112957, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31672375

RESUMO

Parabens are class of preservatives used in vast majority of commercial products, and a potential Endocrine Disrupting Chemical (EDC). The present study was undertaken to delineate the effects of n-butylparaben on F1 male progeny exposed maternally through gestation and lactation via subcutaneous route. The F0 dams were given subcutaneous injections of n-butylparaben from gestation day (GD) 6 to postnatal day (PND) 21 with doses of 10, 100, 1000 mg/kg Bw/day in corn oil. The F1 male rats were monitored for pubertal development and sexual maturation; these were sacrificed on PND 30, 45 and 75. On PND 75, these F1 male rats were subjected for fertility assessment with unexposed female rats. A delayed testicular descent at 100 and 1000 mg/kg Bw dose and delayed preputial separation at 10 mg/kg Bw dose was observed in exposed F1 male rats. Decreased sperm count, motility and Daily Sperm Production was observed at 100 mg/kg Bw dose at PND 75. Interestingly, the sperm transit time in the epididymis was accelerated at this dose. Significant perturbed testicular expression of steroid receptors (ERα and ß, AR), INSL3 and StAR genes with increased T and LH levels indicates direct effect on spermatogenesis and steroidogenesis. These F1 generation adult rats were sub-fertile with increased (%) pre- and post-implantation loss at 100 and 1000 mg/kg Bw/day dose. This is the first report on n-butylparaben highlighting the involvement of testicular leydig cells with accelerated sperm transit time leading to reduced fertility in the maternally exposed F1 male rats through estrogenic/anti-androgenic action.


Assuntos
Disruptores Endócrinos/toxicidade , Fertilidade/efeitos dos fármacos , Parabenos/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Receptores de Esteroides/metabolismo , Espermatogênese/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Lactação , Células Intersticiais do Testículo/efeitos dos fármacos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Receptores de Esteroides/genética , Maturidade Sexual/efeitos dos fármacos , Contagem de Espermatozoides , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/embriologia , Testículo/crescimento & desenvolvimento
8.
J Ethnopharmacol ; 246: 112240, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31526861

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: You-Gui-Yin (YGY) is a famous Chinese traditional medicine compound that has been used to treat renal function diseases for more than 300 years. It is recorded in Jing Yue Quanshu, which was written by a famous medical scientist named Jiebing Zhang in the Ming Dynasty. AIM OF THE STUDY: Reproductive dysfunction is one of the most serious complications of chronic kidney disease (CKD). The aim of this study was to observe the effect of You-Gui-Yin (YGY) on reproductive dysfunction of male rats with adenine-induced CKD and to determine if any effects occurred via regulation of the HIF1α-STAT5 pathway. MATERIALS AND METHODS: UPLC-Q-TOF-MS was used to detect the main medicinal components and conduct quality control of YGY. A total of 60 rats were randomly divided into 2 groups: the NC group (10 rats) and the CKD model group (50 rats). The CKD model rats was established by administration of adenine 150 mg kg-1 orally for 14 days. After that, the CKD rats were randomly divided into 5 groups: the CKD group, YGY (10 g kg-1 group, 20 g kg-1 group, 40 g kg-1 group) and the GUI-LU-ER-XIAN-JIAO (GL) 10 g kg-1 group with 10 rats in each group. From the 15th day to the 45th day rats were given 150 mg kg-1 adenine orally every other day to maintain the model (except in the NC group). The YGY groups and the GL group were orally administered the relevant drug once per day for 30 days. The NC group and the CKD group were orally administered an equal volume of normal saline for 30 days. On the 45th day, the rats' sexual behavior index was tested. On the 46th day, the rats were sacrificed. Biochemical indexes, histopathological changes of the kidneys and testes, sperm morphology, sperm abnormality rate, and key proteins in the HIF1α-STAT5 pathway in the kidney and testis were detected. RESULTS: Thirteen components in the YGY extract were identified by UPLC-Q-TOF-MS for quality control of the YGY extract. The results of the biochemical and physiological tests validated the success of inducing CKD accompanied by reproductive dysfunction in rats. YGY significantly retarded the CKD progression and improved the hormone levels of male CKD rats. Sexual behavior tests showed YGY can significantly improve CKD rats' sexual function. In addition, the pathological changes of the kidney and testis, sperm abnormality rate and sperm morphological abnormalities of the CKD rats were reduced by YGY. Furthermore, decreased expression of HIF1α and EPO, and increased expression of p-EPOR (Tyr368), p-JAK2 (Tyr570) and p-STAT5 (Ser725) were observed in the kidney and the testis of the CKD rats. The YGY extract dramatically increased the expression of HIF1α and EPO, and decreased the expression of p-EPOR (Tyr368), p-JAK2 (Tyr570) and p-STAT5 (Ser725) to regulate key proteins in the HIF1α-STAT5 pathway of the kidney and testis. CONCLUSIONS: YGY has obvious reversal effects on the abnormal symptoms of adenine-induced CKD and the abnormal symptoms of rats with hypothyroidism and male reproductive hypotension. Its mechanism is related to its ability to regulate the HIF1α-STAT5 pathway.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Fator de Transcrição STAT5/metabolismo , Comportamento Sexual Animal/efeitos dos fármacos , Animais , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Masculino , Medicina Tradicional Chinesa , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT5/genética , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos
9.
J Ethnopharmacol ; 247: 112269, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31610261

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cisplatin (CP) is the classical chemotherapeutic drug for various cancer, but it also accompanies reproductive toxicity and genotoxicity. Liuwei Dihuang Pill (LW) is the traditional Chinese medicine prescription for treating Kidney-Yin deficiency syndrome, which has been reported to prevent and treat various diseases. However, the protective effect of LW on CP-induced reproductive toxicity and genotoxicity has not been reported. AIM OF THE STUDY: To investigate the potential protective effect and mechanism of LW on CP-induced reproductive toxicity and genotoxicity in male mice. MATERIALS AND METHODS: Mice were given LW (0.4, 1.2 and 3.6 g/kg) or Vitamin C (0.1 g/kg) once daily by oral gavage for thirteen consecutive days. Then, CP (3.00 mg/kg) was given intraperitoneal injection once daily for five consecutive days starting on the ninth day. The protective effects of LW against CP-induced reproductive toxicity and genotoxicity were evaluated by body weight, testis ratio, sperm count, sperm viability, sperm abnormal morphology type, micronuclei test, testicular histopathology, serum malondialdehyde (MDA), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) level. RESULTS: The results demonstrated that LW could significantly increase CP-induced the reduction of sperm count and sperm viability, then decrease abnormal sperm type rate and micronucleus rate. Moreover, LW also could improve testicular abnormal histopathologic morphology induced by CP exposure. Meanwhile, LW decreased serum MDA level and increased T-SOD, GSH-Px and CAT level compared to CP group. CONCLUSION: our findings show that LW has protective effects on CP-induced reproductive toxicity and genotoxicity. LW decreases serum MDA level and increases T-SOD, GSH-Px and CAT level, which indicates that antioxidant activity may be the potential mechanism of LW to resist reproductive toxicity and genotoxicity.


Assuntos
Antioxidantes/farmacologia , Cisplatino/efeitos adversos , Medicamentos de Ervas Chinesas/farmacologia , Substâncias Protetoras/farmacologia , Animais , Dano ao DNA/efeitos dos fármacos , Humanos , Infertilidade/induzido quimicamente , Infertilidade/prevenção & controle , Masculino , Camundongos , Testes para Micronúcleos , Modelos Animais , Estresse Oxidativo/efeitos dos fármacos , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Testículo/efeitos dos fármacos , Testículo/patologia
10.
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
11.
Ecotoxicol Environ Saf ; 187: 109827, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31655413

RESUMO

Earthworms and their biomarkers are considered good indicators for assessing the effects of toxic chemicals. Therefore, in this study, we exposed Eisenia fetida to lethal and sub-lethal concentrations of Cd and Pb nitrate in artificial soil for 14 and 28 days to evaluate the impact on subcellular partitioning, lethal toxicity (LC50), growth, sperm count, morphology and apoptosis (using TUNEL assay). The soluble internal pools of both metals were good predictors of the responses of biomarkers. We found sperm deformation, TUNEL positive sperms and weight loss positively and sperm count negatively correlated with the concentrations of Cd and Pb in the total internal and cytosolic fraction (p < 0.01) and to a lesser extent with Pb concentrations in the granular fraction (p < 0.05). Fourteen days LC50 for Cd and Pb were 2169 ±â€¯322 and 6387 ±â€¯904 µg/g, respectively. Cadmium and Pb caused a significant depression in sperm count after 14 (Cd: up to 46.9%; Pb: up to 36.24%) and 28 (Cd: up to 72.47%; Pb: up to 43.12%) days of exposure relative to the control (p < 0.05). Cadmium induced higher abnormality in sperm heads than Pb. For both metals, TUNEL positive sperms significantly increased after 14 (Cd: up to 14.17%; Pb: up to 16.33%) and 28 (Cd: up to 16.33%; Pb: up to 11.67%) days of exposure compared with the control (p < 0.05). The findings of this study, illustrate the importance of considering sperm parameters as a rapid, easy and sensitive biomarker for the evaluation of metal toxicity.


Assuntos
Cádmio/toxicidade , Chumbo/toxicidade , Oligoquetos/fisiologia , Poluentes do Solo/toxicidade , Espermatozoides/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Cádmio/metabolismo , Biomarcadores Ambientais/efeitos dos fármacos , Chumbo/metabolismo , Masculino , Oligoquetos/metabolismo , Poluentes do Solo/metabolismo , Espermatozoides/patologia , Frações Subcelulares/metabolismo
12.
Ecotoxicol Environ Saf ; 188: 109908, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31706243

RESUMO

Pesticides have been extensively produced and used to help the agricultural production which leads to the contamination of the environment, soil, groundwater sources, and even foodstuffs. Fungicides carbendazim (CBZ) and chlorothalonil (Chl) are widely applied in agriculture and other aspects. CBZ or Chl have been reported to disrupt spermatogenesis and decrease semen quality. However, it is not understood the effects of pubertal exposure to low doses of CBZ and Chl together, and the underlying mechanisms. Therefore, the aim of current investigation was to explore the negative impacts of pubertal exposure to low doses of CBZ and Chl together on spermatogenesis and the role of epigenetic modifications in the process. We demonstrated that CBZ and Chl together synergize to decrease sperm motility in vitro (CBZ 1.0 + Chl 0.1, CBZ 10.0 + CHl 1.0, CBZ 100.0 + Chl 10 µM in incubation medium for 24 h) and sperm concentration and motility in vivo with ICR mice (CBZ 0.1 + Chl 0.1, CBZ 1.0 + CHl 1.0, CBZ 10.0 + Chl 10 mg/kg body weight; oral gavage for five weeks). CBZ + Chl significantly increase reactive oxygen species (ROS) and apoptosis by the increase in the protein level of caspase 8 in vitro. Moreover, CBZ + Chl synergized to disrupt mouse spermatogenesis with the disturbance in sperm production proteins and sperm proteins (VASA, A-Myb, STK31, AR, Acrosin). CBZ + Chl synergized to decrease the protein level of estrogen receptor alpha and the protein level of DNA methylation marker 5 mC in Leydig cells, and to increase the protein levels of histone methylation marker H3K9 and the methylation enzyme G9a in germ cells. Therefore, greater attention should be paid to the use of CBZ and Chl as pesticides to minimise their adverse impacts on spermatogenesis.


Assuntos
Benzimidazóis/toxicidade , Carbamatos/toxicidade , Epigênese Genética/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Nitrilos/toxicidade , Espermatogênese/efeitos dos fármacos , Animais , Sinergismo Farmacológico , Receptor alfa de Estrogênio/metabolismo , Masculino , Metilação/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Transdução de Sinais/efeitos dos fármacos , Espermatogênese/genética , Espermatozoides/efeitos dos fármacos
13.
Ecotoxicol Environ Saf ; 188: 109847, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31732268

RESUMO

Chlorothalonil is a fungicide present in antifouling paints and other formulations used in agriculture, although studies have shown this chemical to be toxic to fish species. To clarify the deleterious effects of chlorothalonil for these non-target organisms, the present study evaluated the toxic effects of this biocide for the estuarine guppy Poecilia vivipara in terms of an acute mortality test (96 h) and the analysis of biomarkers of oxidative stress, genotoxicity, and sperm quality. The LC50 calculated for P. vivipara was 40.8 µg/L of chlorothalonil. For the analysis of biomarkers, fish were exposed (96 h) to 1 and 10 µg/L of chlorothalonil. It was observed that chlorothalonil alters the levels of pro- and antioxidants towards oxidative stress. In the gills, a negative effect on total antioxidant capacity (ACAP) was detected, while there was a reduction in the activity of glutathione S-transferase (GST) in the liver. However, levels of glutathione (GSH) and the activity and glutamate-cysteine-ligase (GCL) increased in both tissues, as a possible detoxification response. Following chlorothalonil exposure, oxidative damage measured by lipoperoxidation (LPO) significantly increased at the cellular level only (red blood cells (RBCs) and sperm cells). An increase in fluidity of membranes, reactive oxygen species concentration and micronuclei (MNs) incidence were also seen in RBCs. In sperm cells, LPO increased, while membrane and mitochondrial functionality as well as sperm motility decreased. Based on these results, chlorothalonil can be considered as a toxic compound for fish, causing genotoxicity and affecting the RBCs physiology and the fertility of males of P. vivipara.


Assuntos
Biomarcadores/análise , Nitrilos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Poecilia/fisiologia , Espermatozoides/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Dano ao DNA , Desinfetantes/toxicidade , Fungicidas Industriais/toxicidade , Dose Letal Mediana , Masculino , Poecilia/metabolismo , Espermatozoides/fisiologia
14.
PLoS Biol ; 17(12): e3000559, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31877125

RESUMO

The global rise in obesity and steady decline in sperm quality are two alarming trends that have emerged during recent decades. In parallel, evidence from model organisms shows that paternal diet can affect offspring metabolic health in a process involving sperm tRNA-derived small RNA (tsRNA). Here, we report that human sperm are acutely sensitive to nutrient flux, both in terms of sperm motility and changes in sperm tsRNA. Over the course of a 2-week diet intervention, in which we first introduced a healthy diet followed by a diet rich in sugar, sperm motility increased and stabilized at high levels. Small RNA-seq on repeatedly sampled sperm from the same individuals revealed that tsRNAs were up-regulated by eating a high-sugar diet for just 1 week. Unsupervised clustering identified two independent pathways for the biogenesis of these tsRNAs: one involving a novel class of fragments with specific cleavage in the T-loop of mature nuclear tRNAs and the other exclusively involving mitochondrial tsRNAs. Mitochondrial involvement was further supported by a similar up-regulation of mitochondrial rRNA-derived small RNA (rsRNA). Notably, the changes in sugar-sensitive tsRNA were positively associated with simultaneous changes in sperm motility and negatively associated with obesity in an independent clinical cohort. This rapid response to a dietary intervention on tsRNA in human sperm is attuned with the paternal intergenerational metabolic responses found in model organisms. More importantly, our findings suggest shared diet-sensitive mechanisms between sperm motility and the biogenesis of tsRNA, which provide novel insights about the interplay between nutrition and male reproductive health.


Assuntos
Dieta/métodos , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Adulto , Humanos , Masculino , Obesidade/metabolismo , RNA/efeitos dos fármacos , RNA/genética , RNA de Transferência/efeitos dos fármacos , RNA de Transferência/genética , Motilidade Espermática/fisiologia , Espermatozoides/metabolismo , Espermatozoides/fisiologia
15.
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
16.
Life Sci ; 239: 117012, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31678279

RESUMO

BACKGROUND AND PURPOSE: Reduced male fertility has been regarded as a serious complication of rheumatoid arthritis. Phytochemicals have been described as protective agents against rheumatoid arthritis-linked testicular impairment. The current study aimed to investigate the potential protective effects of ellagic acid on rheumatoid arthritis-evoked testicular dysfunction vis-à-vis the reference anti-inflammatory celecoxib. EXPERIMENTAL APPROACH: Ellagic acid (50 mg/kg/day) and celecoxib (5 mg/kg/day) were administered orally for 20 days in adjuvant-induced arthritic rats. KEY FINDINGS: Current data revealed that ellagic acid counteracted rheumatoid arthritis-evoked testicular histopathologic changes, disrupted sperm characteristics and low gonadosomatic index with comparable efficacy to celecoxib. Ellagic acid also enhanced the testicular steroidogenesis via upregulating the gene expression of 3ß-hydroxysteroid dehydrogenase, 17ß-hydroxysteroid dehydrogenase and steroidogenic acute regulatory protein with consequent boosting of serum testosterone. Notably, ellagic acid attenuated the testicular inflammatory responses through suppression of myeloperoxidase, tumor necrosis factor-α and cyclo-oxygenase-2 protein expression together with enhancing the anti-inflammatory signal interleukin 10. Ellagic acid also curbed the redox alterations via lowering the production of lipid peroxides and nitric oxide and elevation of the anti-oxidant reduced glutathione. In support of cell survival, ellagic acid combated testicular apoptosis through downregulating caspase-3 protein expression. SIGNIFICANCE: The present work accentuates the beneficial actions of ellagic acid in rheumatoid arthritis-incurred testicular impairment and disrupted spermatogenesis via combating the inflammatory, oxidative and apoptotic aberrations.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Apoptose/efeitos dos fármacos , Artrite Reumatoide/complicações , Ácido Elágico/farmacologia , Ácido Elágico/uso terapêutico , Doenças Testiculares/tratamento farmacológico , Doenças Testiculares/etiologia , Animais , Caspase 3/efeitos dos fármacos , Celecoxib/farmacologia , Celecoxib/uso terapêutico , Regulação para Baixo/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espermatozoides/efeitos dos fármacos , Esteroides/biossíntese , Testosterona/sangue
17.
Environ Sci Pollut Res Int ; 26(34): 34953-34963, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31664666

RESUMO

The present study evaluated the effects of low doses of atrazine administered during gestation and breastfeeding on sperm characteristics of the wild rodent Calomys laucha. Adult females were divided into groups of 10 and administered different doses of atrazine through gavage, during gestational or breastfeeding period. At 3 months of age, the F1 adult male progeny of these females was evaluated. We observed a drastic reduction in the total and progressive motility of male sperm cells at all doses and during both the exposure periods. Moreover, the plasma membrane integrity of adult male sperm cells decreased at all doses of atrazine administered during the breastfeeding, whereas the membrane fluidity of these cells increased at all tested doses. Atrazine led to a decrease in the sperm mitochondrial functionality at all doses and during both exposure periods. The damage to the sperm DNA was higher in males exposed to the highest dose (1.0 mg/kg) during the gestation period, and in animals exposed to the lowest dose of atrazine (0.1 mg/kg) during breastfeeding period. Furthermore, the highest dose (1.0 mg/kg) of atrazine reduced the sperm concentration. Furthermore, the reduced levels of reactive oxygen species (ROS) were observed at all evaluated doses in males exposed during the gestation period. These results suggest that the administration of low doses of atrazine at critical periods of development may permanently reduce the sperm quality in C. laucha.


Assuntos
Atrazina/toxicidade , Aleitamento Materno , Herbicidas/toxicidade , Espermatozoides/efeitos dos fármacos , Animais , Atrazina/metabolismo , Feminino , Masculino , Fluidez de Membrana , Camundongos , Mitocôndrias , Espécies Reativas de Oxigênio/metabolismo
18.
Arch Ital Urol Androl ; 91(3)2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31577104

RESUMO

OBJECTIVE: The aim of this non controlled trial was to assess whether a therapy with an antioxidant supplement may improve spermatozoa quality in terms of number, motility, morphology and a higher number of successful conceptions in patients with oligoasthenoteratozoospermia undergoing cycles of medically assisted reproduction by intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: 32 patients registered at A.G.I. Medica (Siena) medically assisted reproduction centre affected by fertility problems associated with oligoasthenoteratozoospermia were included in the study. Semen analysis were evaluated according to World Health Organization 2010, before and after treatment. Moreover, we used colorimetric tests to assess oxidative stress. After evaluating oocyte fertilisation rate and the quality of embryos obtained, data were statistically analysed. RESULT: Microscopy examination after the therapy, showed a general improvement in sperm parameters (number of sperms, progressive motility, viability and normal morphology) in both baseline and capacitated; also the levels of oxidative stress was notably lower after the treatment. Morever we evaluated the outcome of the IVF treatment, the percentage of fertilization and the number of embryos obtained, all the parameters was significantly higher in the N1 group. CONCLUSIONS: The outcomes of this trial seem to suggest that the administration of our food supplement improve semen parameters and that the evaluation of oxidative stress levels may become a diagnostic tool to assess male infertility in patients undergoing ART cycle.


Assuntos
Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Oligospermia/tratamento farmacológico , Injeções de Esperma Intracitoplásmicas , Espermatozoides/efeitos dos fármacos , Humanos , Masculino
19.
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
20.
Endocr Regul ; 53(2): 93-99, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31517623

RESUMO

OBJECTIVE: Stem cell therapy, specifically, pre-induction of mesenchymal stem cells toward male germ-like cells may be useful in patients with azoospermia. The aim of this study was to evaluate in vitro differentiation of mouse bone marrow-derived mesenchymal stem cells (BMSCs) into male germ-like cells by indirect co-culture with testicular cells in the presence of bone morphogenetic protein 4 (BMP4). METHODS: Experimental groups included: control (mouse BMSCs), treatment group-1 (BMSCs treated with BMP4), treatment group-2 (indirect co-culture of BMSCs with mouse testicular cells in the presence of BMP4) and treatment group-3 (indirect co-culture of BMSCs with testicular cells). BMSCs-derived male germ-like cells were evaluated by the expression of Dazl, and Stra8 using RT-qPCR. RESULTS: Stra8 gene expression was significantly increased in the treatment group-2 and Dazl gene was significantly increased in the treatment group-1 compared to other groups. In conclusion, indirect co-culturing of BMSCs with testicular cells and BMP4 leads to the differentiation of BMSCs into male germ-like cells which express specific male germ-like genes. Testicular cells released factors that contributed to the differentiation of BMSCs into male germ progenitor cells. CONCLUSION: This study suggests that mesenchymal stem cells may be differentiated into male germ-like cells and therefore, may be a novel treatment option for men with azoospermia.


Assuntos
Proteína Morfogenética Óssea 4/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/citologia , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/fisiologia , Células Cultivadas , Técnicas de Cocultura/métodos , Células Germinativas/efeitos dos fármacos , Células Germinativas/fisiologia , Humanos , Masculino , Células-Tronco Mesenquimais/fisiologia , Camundongos , Espermatozoides/fisiologia
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