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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.
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
3.
J Pharm Biomed Anal ; 177: 112888, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31563758

RESUMO

Metabolomics measurements of seminal plasma are widely used in diagnosis and finding of molecular mechanisms of male infertility. However, so far the limitation of metabolome coverage of analytical methods hinders comprehensive metabolite biomarker finding. Moreover, the widely used case-control comparison is not enough to unveil the detailed correlations of the metabolic changes with different sperm abnormalities. In this work, we aimed to have comprehensive metabolic profiling of seminal plasma to find the metabolomics difference between healthy controls and infertility case samples with different semen abnormities by liquid chromatography-mass spectrometry (LC-MS) detection with previously established new sample preparation procedure. Among 624 detected metabolite features, 63 potential biomarkers in various metabolite classes were found for infertility in seminal plasma by multivariate analysis. Interestingly, different infertility forms have different potential biomarkers with few in common, and most of potential biomarkers were found in oligo-astheno-teratospermia samples. To further find the association of the metabolomic changes with specific sperm abnormality, sperm parameters including sperm concentration, sperm deformity rate and sperm motility were also collected, and multivariate linear regression was used to find correlations between sperm parameters and potential biomarkers. Finally, levels of 17 metabolites were found to be significantly correlated with sperm parameters. Most of correlations agreed with previously reported mechanisms of infertility, such as correlation of acylcarnitines with sperm concentration and sperm deformity, and correlation of some antioxidants with sperm deformity rate and sperm motility. Some correlations were reported for the first time, such as negative correlations of isopentenyl pyrophosphate, 2-phosphoglyceric acid and γ-glutamyl-Se-methylselenocysteine with sperm deformity rate, and negative correlation of creatine riboside with sperm concentration. All the potential biomarkers were involved in 14 metabolic pathways playing important role in energy production, antioxidation, hormone regulation and sperm membrane. These results proved previously reported molecular mechanism (such as oxidative stress and energy production) and also gave new possible clues to the pathology of male infertility, which will benefit future etiology, diagnosis and treatment of male infertility.


Assuntos
Infertilidade Masculina/diagnóstico , Sêmen/metabolismo , Espermatozoides/patologia , Adulto , Biomarcadores/metabolismo , Estudos de Casos e Controles , Membrana Celular/patologia , Metabolismo Energético , Voluntários Saudáveis , Humanos , Infertilidade Masculina/patologia , Masculino , Metaboloma , Metabolômica/métodos , Estresse Oxidativo , Contagem de Espermatozoides , Motilidade Espermática , Espermatozoides/citologia , Espermatozoides/metabolismo , Adulto Jovem
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
6.
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
7.
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
8.
Ecotoxicol Environ Saf ; 186: 109764, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31610356

RESUMO

Crustaceans have been designated as internationally important model organisms in the development of environmental radioprotection measures. Despite the known sensitivity of sperm to ionizing radiation, the impacts of chronic radiation exposure on male fertility in crustaceans have not been studied. For the first time, the present study aimed to assess the impacts of chronic radiation exposure on male fertility, sperm DNA damage and concomitant impacts on breeding in two amphipod crustaceans. Echinogammarus marinus and Gammarus pulex (male fertility only) were exposed to phosphorus-32 at dose rates of 0, 0.1, 1 and 10 mGy/d and sperm parameters, DNA damage and knock-on impacts on breeding were assessed. Sperm quality parameters and DNA damage were assessed using a fluorescent staining method and single cell gel electrophoresis respectively. Concomitant effects of male exposure to radiation on fecundity were determined by pairing phosphorus-32 exposed males to unexposed sexually mature females. In E. marinus, a statistically significant reduction of 9 and 11% in the quality of sperm was recorded at dose rates of 1 and 10 mGy/d respectively, with no significant effects recorded on sperm counts. Conversely in the freshwater G. pulex, no significant impact of radiation on sperm quantity or quality was recorded. For E. marinus, a statistically significant increase in DNA damage was recorded at doses of 10 mGy/d. Reduced fecundity and an increase in the frequency of abnormal embryos was recorded in female E. marinus breeding with males exposed to radiation. These findings suggest sperm quality may be a sensitive indicator of radiation exposure in invertebrates with potential impacts on the unexposed embryo, though unclear dose-response and differences between two closely related species necessitate further study before robust conclusions can be drawn.


Assuntos
Anfípodes/efeitos da radiação , Dano ao DNA , Radiação Ionizante , Espermatozoides/efeitos da radiação , Anfípodes/genética , Anfípodes/crescimento & desenvolvimento , Animais , Feminino , Fertilidade/efeitos da radiação , Água Doce , Masculino , Água do Mar , Espermatozoides/patologia
9.
Chemosphere ; 226: 874-882, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31509916

RESUMO

The exposure and health effects of fluoride are an ongoing topic that has attracted worldwide attention. Fluoride exposure disturbs the testicular development, sexual hormone levels and spermatogenesis. However, as to whether fluoride interferes with acrosome formation which is essential for production of capable spermatozoa during spermatogenesis still remains unclear. The objective was to determine the effects of fluoride on the acrosome formation and to further elucidate the potential mechanism of impaired reproductive function. For this, forty adult rats were assigned into four groups. The control group received distilled water, while the other three groups were treated with 25, 50 and 100 mg NaF/L via drinking water for 56 d, respectively. Testes were processed for total RNA extraction and western blot analysis. Three samples of each group were fixed in 2.5% glutaraldehyde solution for transmission electron microscopy analysis. From the results, we first found that fluoride decreased the expression of mRNA and protein levels of Zpbp1, Spaca1 and Dpy19l2 of seven markers during acrosome biogenesis in testes. Furthermore, fluoride damaged not only the acrosome structure, but also the structure of the nuclear lamina which was observed to be discontinuous and partially missing by transmission electron microscopy. Moreover, the results indicated that the altered structure in nuclear lamina maybe due to reduced LMNB2 expression in testis induced by fluoride. In a nutshell, fluoride exposure could restrain acrosome biogenesis during spermatogenesis and contribute to the elucidation of the underlying mechanisms of fluoride-induced male reproductive toxicity.


Assuntos
Acrossomo/patologia , Fluoretos/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/patologia , Testículo/patologia , Acrossomo/efeitos dos fármacos , Acrossomo/metabolismo , Animais , Proteínas do Ovo/genética , Proteínas do Ovo/metabolismo , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas de Plasma Seminal/genética , Proteínas de Plasma Seminal/metabolismo , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo
10.
Environ Pollut ; 255(Pt 1): 113097, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31520908

RESUMO

Decabromodiphenyl ether (BDE-209) is commonly used as a flame retardant, usually in products that were utilized in electronic equipment, plastics, furniture and textiles. To identify the impacts of BDE-209 on the male reproductive system and the underlying toxicological mechanisms, 40 male ICR mice were randomly divided into four groups, which were then exposed to BDE-209 at 0, 7.5, 25 and 75 mg kg-1 d-1 for four weeks, respectively. With regard to the in vitro study, GC-2spd cells were treated with BDE-209 at 0, 2, 8 and 32 µg mL-1 for 24 h, respectively. The results from the in vivo experiments showed that BDE-209 resulted in damage to the testis structure, led to cell apoptosis in testis and decreased sperm number and motility, while sperm malformation rates were significantly increased. Moreover, BDE-209 could induce oxidative stress with decreased testosterone levels, result in DNA damage and activate DNA damage response signaling pathways (ATM/Chk2, ATR/Chk1 and DNA-PKcs/XRCC4/DNA ligase Ⅳ). The data from the in vitro experiments showed that BDE-209 led to cytotoxicity by reducing cell viability and increasing LDH release as well. BDE-209 also induced DNA strand breaks, cell cycle arrest at G1 phase and elevated reactive oxygen species (ROS) level in GC-2 cells. These results suggested that BDE-209 could lead to male reproductive toxicity by inducing DNA damage and failure of DNA damage repair which resulted in cell cycle arrest and apoptosis of spermatogenic cell. The present study provided new evidence to elucidate the potential mechanism of male reproductive toxicity induced by BDE-209.


Assuntos
Apoptose/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Retardadores de Chama/toxicidade , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Éteres Difenil Halogenados/toxicidade , Espermatozoides/patologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Reparo do DNA/genética , Masculino , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/citologia , Testículo/citologia , Testículo/patologia , Testosterona/sangue
11.
Environ Pollut ; 255(Pt 1): 113172, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31541822

RESUMO

Researches had shown that silica nanoparticles (SiNPs) could reduce the quantity and quality of sperms. However, chronic effects of SiNPs have not been well addressed. In this study, mice spermatocyte cells (GC-2spd cells) were continuously exposed to SiNPs (5 µg/mL) for 30 passages and then the changes of microRNA (miRNA) profile and mRNA profile were detected. The function of miRNAs was verified by inhibitors to explore the regulation role of miRNAs in reproductive toxicity induced by SiNPs. The results showed that SiNPs induced cytotoxicity, and activated autophagy in GC-2spd cells. SiNPs led to a total of 1604 mRNAs (697 up-regulated and 907 down-regulated) and 15 miRNAs (6 up-regulated such as miRNA-138 and miRNA-494 and 9 down-regulated) with different expression in GC-2spd cells. The combined miRNA profile and mRNA profile showed that 415 mRNAs with different expression in 5 µg/mL SiNPs group were regulated by miRNA. Furthermore, our study demonstrated that SiNPs decreased the expressions of AKT mRNAs. Moreover, SiNPs had an activation effect on the AMPK/TSC/mTOR pathway. However, inhibitor of miRNA-494 could attenuate the expression levels of AMPK, TSC, LC3Ⅱ and alleviate the decreased of AKT, mTOR, p-mTOR induced by SiNPs. The above results suggested that the low-dose SiNPs exposure could promote autophagy by miRNA-494 targeting AKT, thereby activating AMPK/TSC/mTOR pathway in GC-2spd cells. MiRNA-494 is an important regulator of autophagy by targeting AKT, which provides new evidence for the male reproductive toxicity mechanism of SiNPs.


Assuntos
Autofagia/efeitos dos fármacos , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Dióxido de Silício/toxicidade , Espermatozoides/patologia , Animais , Linhagem Celular , Regulação para Baixo , Masculino , Camundongos , Nanopartículas/toxicidade , Análise do Sêmen , Espermatócitos , Espermatozoides/efeitos dos fármacos , Regulação para Cima
12.
Molecules ; 24(18)2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31547465

RESUMO

The aim is to explore the mechanism of the apoptosis signal-regulating kinase-1 (ASK-1) signaling pathway and the involvement of the thioredoxin (Trx) system during testicular ischemia reperfusion injury (tIRI) by using ASK-1 specific inhibitor, NQDI-1. Male Sprague-Dawley rats (n = 36, 250-300 g) were equally divided into 3 groups: sham, tIRI, and tIRI + NQDI-1 (10 mg/kg, i.p, pre-reperfusion). For tIRI induction, the testicular cord and artery were occluded for 1 h followed by 4 h of reperfusion. Histological analyses, protein immunoexpression, biochemical assays, and real-time PCR were used to evaluate spermatogenesis, ASK-1/Trx axis expression, enzyme activities, and relative mRNA expression, respectively. During tIRI, ipsilateral testes underwent oxidative stress indicated by low levels of superoxide dismutase (SOD) and Glutathione (GSH), increased oxidative damage to lipids and DNA, and spermatogenic damage. This was associated with induced mRNA expression of pro-apoptosis genes, downregulation of antiapoptosis genes, increased caspase 3 activity and activation of the ASK-1/JNK/p38/survivin apoptosis pathway. In parallel, the expression of Trx, Trx reductase were significantly reduced, while the expression of Trx interacting protein (TXNIP) and the NADP+/ nicotinamide Adenine Dinucleotide phosphate (NADPH) ratio were increased. These modulations were attenuated by NQDI-1 treatment. In conclusion, the Trx system is regulated by the ASK-1/Trx/TXNIP axis to maintain cellular redox homeostasis and is linked to tIRI-induced germ cell apoptosis via the ASK-1/JNK/p38/survivin apoptosis pathway.


Assuntos
Aporfinas/farmacologia , MAP Quinase Quinase Quinase 5/metabolismo , Quinolinas/farmacologia , Traumatismo por Reperfusão/metabolismo , Espermatozoides/metabolismo , Tiorredoxinas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Proteínas de Ciclo Celular/metabolismo , MAP Quinase Quinase 4/metabolismo , MAP Quinase Quinase Quinase 5/antagonistas & inibidores , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Survivina/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
Med Sci Monit ; 25: 6727-6735, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31493333

RESUMO

BACKGROUND The aim of this study was to investigate the effect of Cuscuta chinensis Lam. on germ cell apoptosis in a rat model of unilateral cryptorchidism. MATERIAL AND METHODS Thirty male SD rats were randomly and equally divided into a control group, a model group, and a Cuscuta group (5.0 g/kg/d) (n=10). The rat model of unilateral cryptorchidism in the model and Cuscuta groups was established by removal of the right gubernaculum, while rats in the control group received no treatment. After modeling, rats in the Cuscuta chinensis group were intragastrically administered Cuscuta chinensis extract (5.0 g/kg/d), while rats in the control group and model group were administered an equal volume of normal saline. After 90 days, all the rats were sacrificed and the testicles were separated and weighed, followed by TUNEL staining to detect germ cell apoptosis, flow cytometry to measure JC-1, ROS, and MDA, and Western blot analysis to evaluate the expression of Bax, Bcl-2, and cleaved caspase3. RESULTS Ninety days after the operation, Cuscuta chinensis Lam significantly minimized the damage caused by modeling by increasing weight of testis, reducing the germ cell apoptosis, and enhancing the mitochondrial membrane potential of testicles, as shown by levels of JC-1, ROS, and MDA, as well as elevating the level of Bcl-2/Bax and reducing the level of cleaved caspase3 (P<0.05). CONCLUSIONS Treatment with Cuscuta chinensis Lam reduced the germ cell apoptosis in rats with unilateral cryptorchidism, which provides new insight for the development of cryptorchidism therapy in the future.


Assuntos
Criptorquidismo/tratamento farmacológico , Cuscuta/química , Extratos Vegetais/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Criptorquidismo/patologia , Modelos Animais de Doenças , Masculino , Malondialdeído/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Testículo/efeitos dos fármacos , Testículo/patologia , Proteína X Associada a bcl-2/metabolismo
14.
Artigo em Inglês | MEDLINE | ID: mdl-31394254

RESUMO

The present study aimed to evaluate the protective role of Selenium (Se) (0.1 ppm) on the male reproductive system of the catfish Clarias gariepinus exposed to sublethal doses of Mercury (Hg) (0.04 and 0.12 ppm) for 30 days. Indicators of seminal and gonadal hormone disruption (testosterone, estradiol and 11 keto testosterone), antioxidants (total antioxidant capacity (TAO), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)), oxidative stress biomarkers (lipid peroxidation (LPO), percentage of DNA fragmentation, carbonylated proteins (CP) and nitric oxide (NO)) and histopathological alterations in testicles of Clarias gariepinus were determined. The exposure to Hg resulted in a high accumulation of residues of this metal in testicular tissues. The results showed a significant decrease in sperm count, activity and motility and in all gonadal hormones in Hg exposed groups. Hg exposure also induced a decline in TAO, SOD, CAT and GPx, whereas LPO, DNA fragmentation, CP and NO significantly increased in testicles of C. gariepinus respect to the control group. Although exposure to Se did not reduce the degree of mercury bioconcentration in the testicles, the sperm quality parameters were recovered. Moreover, TAO levels and GPx activity significantly increased after fish exposure to Se, whereas CP levels decreased. LPO, NO, CAT and SOD were also partially normalized when compared with the groups exposed to only Hg. In conclusion, the results showed that Hg, even in the small doses is capable to induce reproductive toxicity in the male catfish. Se exposure partially restored the values of biochemical parameters and sperm quality in Hg-treated fish suggesting protective effects against Hg reproductive toxicity.


Assuntos
Peixes-Gato/metabolismo , Mercúrio/toxicidade , Selênio/farmacologia , Espermatozoides , Testículo , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Hormônios Gonadais/metabolismo , Masculino , Intoxicação por Mercúrio/tratamento farmacológico , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Testículo/efeitos dos fármacos , Testículo/patologia , Poluentes Químicos da Água/toxicidade
15.
Zygote ; 27(5): 263-271, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31412971

RESUMO

Infertility is an important reproductive health problem, and male infertility is especially important in more than half of infertility cases. Due to the importance of genetic factors in this condition, analysis of semen alone is not enough to recognize men with idiopathic infertility. A molecular non-invasive investigation is necessary to gain valuable information. Currently, microRNAs (miRNAs) are being used as non-invasive diagnostic biomarkers. miRNAs, single-stranded non-coding RNA molecules, act as post-transcriptional gene silencing regulators either by inhibition or repression of translation. Changes in the regulation of miRNAs have been investigated in several different types of male infertility, therefore the biological role of miRNA and gene targets has been defined. The purpose of this study was to review recent research on the altered expression of miRNA in semen, sperm, and testicular biopsy samples in infertile males with different types of unexplained infertility. Changes in miRNA regulation were investigated using microarray and the miRNA levels were confirmed by real-time qRT-PCR. This review explains why creating a non-invasive diagnostic method for male infertility is necessary and how changes in miRNA expression can be used as new diagnostic biomarkers in patients with differing spermatogenic and histopathologic injury.


Assuntos
Infertilidade Masculina/genética , MicroRNAs/genética , Espermatogênese/genética , Regulação da Expressão Gênica , Humanos , Infertilidade Masculina/diagnóstico , Masculino , Espermatozoides/patologia , Espermatozoides/fisiologia
16.
Nutrients ; 11(9)2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31450760

RESUMO

The objective was to determine effects of feed restriction and refeeding on reproductive development and energy balance in pre-pubertal male rats. Sprague Dawley rats (n = 32, 24 days old, ~65 g), were randomly allocated into four treatments (n = 8/treatment): (1) Control (CON, ad libitum feed; (2) Mild Restriction (MR, rats fed 75% of CON consumption); (3) Profound Restriction (PR, 50% of CON consumption); or (4) Refeeding (RF, 50% restriction for 14 days, and then ad libitum for 7 days). Feed restriction delayed reproductive development and decreased energy balance and tissue accretion, with degree of reproductive and metabolic dysfunctions related to restriction severity. In RF rats, refeeding largely restored testis weight, sperm production (per gram and total), plasma IGF-1, leptin and insulin concentrations and energy expenditure, although body composition did not completely recover. On Day 50, more CON and RF rats than PR rats were pubertal (5/6, 4/5 and 1/6, respectively; plasma testosterone >1 ng/mL) with the MR group (4/6) not different. Our hypothesis was supported: nutrient restriction of pre-pubertal rats delayed reproductive development, induced negative energy balance and decreased metabolic hormone concentrations (commensurate with restriction), whereas short-term refeeding after profound restriction largely restored reproductive end points and plasma hormone concentrations, but not body composition.


Assuntos
Restrição Calórica , Metabolismo Energético , Desenvolvimento Sexual , Testículo/crescimento & desenvolvimento , Fatores Etários , Animais , Biomarcadores/sangue , Composição Corporal , Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Leptina/sangue , Masculino , Estado Nutricional , Ratos Sprague-Dawley , Motilidade Espermática , Espermatozoides/metabolismo , Espermatozoides/patologia , Testículo/metabolismo
17.
Arch Ital Urol Androl ; 91(2)2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266282

RESUMO

OBJECTIVE: This exploratory retrospective study aimed to compare the level of Sperm DNA Fragmentation (SDF) and investigate its association with bulk semen parameters, for the first time in Bulgarian patients with varicocele, using a distinct methodology. MATERIAL AND METHODS: Standard semen analysis was performed according to the 2010 criteria of the European Society of Human Reproduction and Embryology - Nordic Association for Andrology (ESHRE-NAFA-2010) and DNA fragmentation was assessed using the Halosperm® kit. The total sample included 28 males: the control group consisted of men with normal genital examination and unknown fertility (n = 10), group one consisted of men with varicocele, normozoospermia and DNA fragmentation > 15% (n = 9) and group two consisted of men with varicocele, abnormal sperm parameters and DNA fragmentation > 15% (n = 9). RESULTS: DNA fragmentation was found to be higher in patients with abnormal sperm parameters (43.78 ± 30.78) compared to the normozoospermic group (21.22 ± 3.93) (p = 0.008). In normozoospermic patients, no statistically significant correlations were observed between SDF and bulk semen parameters. In patients with abnormal sperm parameters, DNA fragmentation exhibited significant very strong negative association with motility (a+b), vitality and typical morphology (p < 0.001). CONCLUSIONS: DNA integrity assays could be used for a better evaluation and management of male infertility, particularly in normozoospermic varicocele patients.


Assuntos
Fragmentação do DNA , Sêmen/metabolismo , Espermatozoides/metabolismo , Varicocele/complicações , Adulto , Bulgária , Humanos , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/etiologia , Masculino , Estudos Retrospectivos , Análise do Sêmen , Motilidade Espermática , Espermatozoides/patologia , Adulto Jovem
18.
Andrologia ; 51(9): e13362, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31321807

RESUMO

Formaldehyde is a common agent in our surrounding environment and can adversely affect the male reproductive system. In this study, the effectiveness of Matricaria chamomilla (MC) extract as an antioxidant was investigated in rats treated with formaldehyde. Thirty-two male Wistar rats were randomly divided into six groups: F (10 mg/kg formaldehyde), M200 (200 mg/kg MC extract), M500 (500 mg/kg MC extract), FM200 (10 mg/kg formaldehyde and 200 mg/kg MC extract), FM500 (10 mg/kg formaldehyde and 500 mg/kg MC extract) and control group (0.9% normal saline). Formaldehyde and MC extract were administered daily for 30 consecutive days via intraperitoneal injection. Hormonal status, sperm parameters, testis tissue histology, germinal cells apoptosis and stereological analyses of testis tissue were investigated. Testosterone and LH levels were significantly increased in FM200, FM500, F200 and F500 groups compared to F group (p ≤ 0.05). Sperm count, motility and viability were significantly enhanced in FM200, FM500, F200 and F500 groups compared to F group (p ≤ 0.05). A decrease in the number of apoptotic germ cells in FM200, FM500, M200 and M500 groups (p ≤ 0.05) was evident. In particular, the MC extract in dose 500 mg/kg is seen to reduce the adverse effects of formaldehyde on the reproductive system of male rats.


Assuntos
Antioxidantes/administração & dosagem , Formaldeído/toxicidade , Infertilidade Masculina/tratamento farmacológico , Matricaria/química , Extratos Vegetais/administração & dosagem , Animais , Antioxidantes/isolamento & purificação , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Etanol/química , Humanos , Infertilidade Masculina/induzido quimicamente , Masculino , Extratos Vegetais/isolamento & purificação , Ratos , Ratos Wistar , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Testículo/efeitos dos fármacos , Testículo/patologia , Água/química
19.
Adv Exp Med Biol ; 1166: 75-85, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31301047

RESUMO

Spermatozoa have the task to deliver an intact paternal genome to the oocyte and to support a successful embryo development. The high levels of sperm DNA fragmentation (sDF) found in sub-/infertile men threat human reproduction and health of the offspring. Strategies to prevent the onset of this type of sperm damage are extensively sought.sDF can be induced by factors like lifestyle-related habits, diseases, drugs, aging, infections and exposure to pollutants. At the cell level, all these factors induce sperm DNA breaks by three main mechanisms: apoptosis, impairment of sperm chromatin maturation and oxidative stress. Apoptosis and defects in maturation of sperm chromatin appear to act in the testis and account for DNA breaks found in dead ejaculated spermatozoa, whereas oxidative stress is likely inducing sDF during the transit through the male genital tracts and accounting for DNA breaks observed in viable spermatozoa of the ejaculate. Oxidative stress appears to be also the main mechanism responsible for induction of sDF after ejaculation, during in vitro manipulation of spermatozoa. Whether or not mature spermatozoa are able to trigger a cell death program is not yet clarified. In particular, it is not clear whether apoptotic nucleases or reactive oxygen species are responsible for producing DNA breaks in ejaculated mature spermatozoa. Knowledge of the mechanisms inducing sDF is a valuable starting point to define possible therapeutic options that however are still far to be established.


Assuntos
Fragmentação do DNA , Espermatozoides , Humanos , Masculino , Maturação do Esperma , Espermatozoides/patologia , Testículo
20.
Adv Exp Med Biol ; 1166: 87-105, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31301048

RESUMO

DNA fragmentation, or the accumulation of single- and double-strand DNA breaks, is a common property of sperm, and an increase in the level of sperm DNA fragmentation is known to influence natural reproduction. The effect of sperm DNA fragmentation on male infertility and assisted reproductive treatment (ART) outcomes remains controversial and is one of the most frequently debated topics of reproductive medicine. For the past 30 years, a number of assays have been developed to quantify the level of sperm DNA fragmentation. In this chapter, we review the causes of sperm DNA fragmentation, describe the commonly used tests to evaluate these abnormalities, and perform a systematic review of existing studies to determine the impact of sperm DNA fragmentation on male fertility and ART outcomes.


Assuntos
Fragmentação do DNA , Infertilidade Masculina , Reprodução , Espermatozoides , Feminino , Humanos , Masculino , Reprodução/genética , Técnicas de Reprodução Assistida , Espermatozoides/patologia , Resultado do Tratamento
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