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1.
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
2.
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
3.
Chemosphere ; 238: 124650, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31472347

RESUMO

Arsenic (As) has become a major problem in maintaining the environment and human health due to its wide application in the production of agriculture and industry. Many studies indicate that As can affect spermatogenesis process and lower sperm quality. However, the undergoing molecular mechanism is unclear. For this, forty-eight 8-week old adult male mice were divided into four groups of twelve each, which were administrated to 0, 0.2, 2, 20 ppm As2O3 in their drinking water respectively for six months. The results showed that As treatment reduced sperm counts and increased the sperm malformation ratio of mice. Interestingly, both the amounts of round and elongated spermatids, and the ratios of spermatids elongation were decreased significantly by As exposure. Furthermore, the structure of Chromatoid Body (CB) which presents a typical nebulous shape in round spermatids after spermatogenesis arrested, and the mRNA expression levels of gene TDRD1, TDRD6 and TDRD7 related to CB were changed by arsenic. Again, the mRNA and protein expression levels of the markers DDX25 and CRM1 in haploid periods of spermatogenesis and the associated proteins HMG2, PGK2, and H4 with DDX25 regulation were declined significantly with As treatment. Taken together; it reveals that As interferes with spermatogenesis by disorganizing the elongation of spermatids. H4, HMG2 and PGK2 are regulated by DDX25 which interacts with CRM1 and may play a vital role in spermatogenesis disorder induced by As exposure, which maybe provides one of the underlying mechanisms for As-induced male reproductive toxicity.


Assuntos
Arsênico/toxicidade , Espermátides/patologia , Espermatogênese/efeitos dos fármacos , Envelhecimento , Animais , Proteínas de Ciclo Celular/genética , RNA Helicases DEAD-box/genética , Perfilação da Expressão Gênica , Masculino , Camundongos , RNA Mensageiro/metabolismo , Espermátides/efeitos dos fármacos , Espermatozoides/metabolismo
4.
Gene ; 725: 144161, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31639432

RESUMO

Bivalve species with doubly uniparental inheritance of mitochondria have been shown to contain additional mtDNA-encoded proteins suspected to be involved in sex-specific transmission of the female (F) and male (M) mitochondrial genomes. This is true for freshwater mussels and marine clams but was still unclear for marine mussel Mytilus spp. Here we present evidence that a F mtDNA-specific open reading frame (ORF) identified in the control region of M. edulis codes for a protein. The protein was detected, using western blots, in both female and male mantle tissues, which contain the gonads. The protein was also localized, using immunochemistry, in sperm mitochondria.


Assuntos
DNA Mitocondrial/genética , Mytilus/genética , Animais , Bivalves/genética , Feminino , Genoma Mitocondrial/genética , Masculino , Mitocôndrias/genética , Fases de Leitura Aberta/genética , Fatores Sexuais , Espermatozoides/metabolismo
5.
BMC Evol Biol ; 19(1): 214, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771505

RESUMO

BACKGROUND: The buffalo, despite its superior milk-producing ability, suffers from reproductive limitations that constrain its lifetime productivity. Male sub-fertility, manifested as low conception rates (CRs), is a major concern in buffaloes. The epididymal sperm surface-binding proteins which participate in the sperm surface remodelling (SSR) events affect the survival and performance of the spermatozoa in the female reproductive tract (FRT). A mutation in an epididymal secreted protein, beta-defensin 126 (DEFB-126/BD-126), a class-A beta-defensin (CA-BD), resulted in decreased CRs in human cohorts across the globe. To better understand the role of CA-BDs in buffalo reproduction, this study aimed to identify the BD genes for characterization of the selection pressure(s) acting on them, and to identify the most abundant CA-BD transcript in the buffalo male reproductive tract (MRT) for predicting its reproductive functional significance. RESULTS: Despite the low protein sequence homology with their orthologs, the CA-BDs have maintained the molecular framework and the structural core vital to their biological functions. Their coding-sequences in ruminants revealed evidence of pervasive purifying and episodic diversifying selection pressures. The buffalo CA-BD genes were expressed in the major reproductive and non-reproductive tissues exhibiting spatial variations. The Buffalo BD-129 (BuBD-129) was the most abundant and the longest CA-BD in the distal-MRT segments and was predicted to be heavily O-glycosylated. CONCLUSIONS: The maintenance of the structural core, despite the sequence divergence, indicated the conservation of the molecular functions of the CA-BDs. The expression of the buffalo CA-BDs in both the distal-MRT segments and non-reproductive tissues indicate the retention the primordial microbicidal activity, which was also predicted by in silico sequence analyses. However, the observed spatial variations in their expression across the MRT hint at their region-specific roles. Their comparison across mammalian species revealed a pattern in which the various CA-BDs appeared to follow dissimilar evolutionary paths. This pattern appears to maintain only the highly efficacious CA-BD alleles and diversify their functional repertoire in the ruminants. Our preliminary results and analyses indicated that BuBD-129 could be the functional ortholog of the primate DEFB-126. Further studies are warranted to assess its molecular functions to elucidate its role in immunity, reproduction and fertility.


Assuntos
Búfalos/genética , Búfalos/fisiologia , beta-Defensinas/genética , Animais , Simulação por Computador , Feminino , Fertilidade , Humanos , Masculino , Modelos Moleculares , Filogenia , Reprodução , Seleção Genética , Espermatozoides/metabolismo , beta-Defensinas/química , beta-Defensinas/metabolismo
6.
Photochem Photobiol Sci ; 18(12): 2893-2900, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31681924

RESUMO

Photo-modulation with visible light has been used to induce gains in the motility of the sperms of rabbits, boars, buffalo, bulls, fish, and humans. Although different hypotheses have been proposed to explain such an effect, the origin and mechanisms by which visible light affects sperm motility are still far from being completely understood. Several groups have observed changes in the intracellular Ca2+ concentration and significant differences in the production of ROS, which are attributed to specific photosensitizers. Also, it has been reported that blue light induces nitric oxide production in sperm cells, which plays a vital role in acrosome reaction and capacitation leading to an augmentation in the fertilisation probability. In the present work, we study the effects of green light (490-540 nm) on the sperm motility of mice. Firstly, we carried out experiments at 37 °C to confirm what previous researchers have observed before using red and blue light: that the overall sperm motility increases. Secondly, we studied the effects of green light at 10 °C and found that the motility drastically diminishes. In order to understand this opposing outcome, we carried out fluorescence measurements to evaluate reactive oxygen species production induced by green light at both temperatures. Our results suggest that the balance between the use and generation of ROS at 37 °C is favorable to the cells, while at 10 °C it is harmful.


Assuntos
Luz , Motilidade Espermática/efeitos da radiação , Espermatozoides/metabolismo , Animais , Masculino , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Espermatozoides/efeitos da radiação , Temperatura Ambiente
7.
Nat Commun ; 10(1): 4705, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31624244

RESUMO

DNA methylation, repressive histone marks, and PIWI-interacting RNA (piRNA) are essential for the control of retrotransposon silencing in the mammalian germline. However, it remains unknown how these repressive epigenetic pathways crosstalk to ensure retrotransposon silencing in the male germline. Here, we show that UHRF1 is responsible for retrotransposon silencing and cooperates with repressive epigenetic pathways in male germ cells. Conditional loss of UHRF1 in postnatal germ cells causes DNA hypomethylation, upregulation of retrotransposons, the activation of a DNA damage response, and switches in the global chromatin status, leading to complete male sterility. Furthermore, we show that UHRF1 interacts with PRMT5, an arginine methyltransferase, to regulate the repressive histone arginine modifications (H4R3me2s and H3R2me2s), and cooperates with the PIWI pathway during spermatogenesis. Collectively, UHRF1 regulates retrotransposon silencing in male germ cells and provides a molecular link between DNA methylation, histone modification, and the PIWI pathway in the germline.


Assuntos
Proteínas Argonauta/genética , Proteínas Estimuladoras de Ligação a CCAAT/genética , Metilação de DNA , Proteína-Arginina N-Metiltransferases/genética , Retroelementos/genética , Espermatozoides/metabolismo , Ubiquitina-Proteína Ligases/genética , Animais , Proteínas Argonauta/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Feminino , Inativação Gênica , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Ligação Proteica , Proteína-Arginina N-Metiltransferases/metabolismo , Espermatogênese/genética , Ubiquitina-Proteína Ligases/metabolismo
8.
Environ Pollut ; 255(Pt 2): 113317, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31610502

RESUMO

Aflatoxin B1 (AFB1) is a hazard environmental pollutants and the most toxic one of all the aflatoxins. AFB1 can cause a serious impairment to testicular development and spermatogenesis, yet the underlying mechanisms remain inconclusive. Oxidative stress acts as a master mechanism of AFB1 toxicity, and can promote autophagy. Abnormal autophagy resulted in testicular damage and spermatogenesis disorders. The objective of this study was to explore the effect of AFB1 on autophagy in mice testis and its potential mechanisms. In this study, male mice were intragastrically administered with 0, 0.375, 0.75 or 1.5 mg/kg body weight AFB1 for 30 days. We found that AFB1 induced testicular damage, reduced serum testosterone level and impaired sperm quality accompanied with the elevation of oxidative stress and germ cell apoptosis. Interestingly, we observed increasing numbers of autophagosomes in AFB1-exposed mice testis. Meanwhile, AFB1 caused testis abnormal autophagy with the characterization of increased expressions of LC3, Beclin-1, Atg5 and p62. Furthermore, AFB1 downregulated the expressions of PI3K, p-AKT and p-mTOR in mice testis. Taken together, our data indicated AFB1 induced testicular damage and promoted autophagy, which were associated with oxidative stress-related PI3K/AKT/mTOR signaling pathway in mice testis.


Assuntos
Aflatoxina B1/toxicidade , Autofagia/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Testículo/patologia , Animais , Apoptose/efeitos dos fármacos , Autofagossomos/efeitos dos fármacos , Proteína Beclina-1/metabolismo , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Espermatogênese/fisiologia , Espermatozoides/metabolismo , Testículo/embriologia , Testosterona/sangue
9.
Nat Commun ; 10(1): 4456, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31575859

RESUMO

Fertilization is essential for species survival. Although Izumo1 and Juno are critical for initial interaction between gametes, additional molecules necessary for sperm:egg fusion on both the sperm and the oocyte remain to be defined. Here, we show that phosphatidylserine (PtdSer) is exposed on the head region of viable and motile sperm, with PtdSer exposure progressively increasing during sperm transit through the epididymis. Functionally, masking phosphatidylserine on sperm via three different approaches inhibits fertilization. On the oocyte, phosphatidylserine recognition receptors BAI1, CD36, Tim-4, and Mer-TK contribute to fertilization. Further, oocytes lacking the cytoplasmic ELMO1, or functional disruption of RAC1 (both of which signal downstream of BAI1/BAI3), also affect sperm entry into oocytes. Intriguingly, mammalian sperm could fuse with skeletal myoblasts, requiring PtdSer on sperm and BAI1/3, ELMO2, RAC1 in myoblasts. Collectively, these data identify phosphatidylserine on viable sperm and PtdSer recognition receptors on oocytes as key players in sperm:egg fusion.


Assuntos
Oócitos/metabolismo , Fagócitos/metabolismo , Fosfatidilserinas/metabolismo , Interações Espermatozoide-Óvulo/fisiologia , Espermatozoides/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Angiogênicas/metabolismo , Animais , Antígenos CD36/metabolismo , Proteínas do Citoesqueleto/metabolismo , Epididimo , Feminino , Humanos , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Mioblastos Esqueléticos , Proteínas do Tecido Nervoso/metabolismo , Neuropeptídeos/metabolismo , Fosfatidilserinas/genética , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , c-Mer Tirosina Quinase/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo
10.
Medicine (Baltimore) ; 98(41): e17494, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593115

RESUMO

BACKGROUND: Infertility has troubled the world's 186 million people, and male infertility accounts for more than half. The literature of physical exercise related to semen quality has shown inconsistent results, and there is currently no systematic review to evaluate the effects of exercise on reproductive outcomes in male infertility patients. This study aims to assessing the effects of exercise interventions based on randomized controlled trials (RCTs) on semen quality and reproductive outcomes in male infertility. METHODS: English and Chinese literature about physical exercise treatment for male infertility published before July 31, 2019 will be systematic searched in PubMed, Embase, Web of Science, Cochrane Library, Open Grey, Clinicaltrials.gov, Chinese Clinical Trial Registry, WANFANG, VIP Chinese Science and Technology Journal Database, CNKI, Chinese biomedical document service system (SinoMed). Only RCTs of patients with male infertility will be included. Literature screening, data extraction, and the assessment of risk of bias will be independently conducted by 2 reviewers, and the 3rd reviewer will be consulted if any different opinions existed. Live-birth rate, pregnancy rate, adverse events (including miscarriage), sperm concentration, progressive motility, sperm morphology, and sperm DNA fragmentation will be evaluated. Systematic review and meta-analysis will be produced by RevMan 5.3 and Stata 14.0. This protocol reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) statement, and we will report the systematic review by following the PRISMA statement. CONCLUSION AND DISSEMINATION: We will assess the efficacy and safety of physical exercise on semen quality and reproductive outcomes in infertile men. The findings will be published in a peer-reviewed journal to provide evidence-based medical evidence for clinical decision making and the patient's lifestyle guidance. REGISTRATION INFORMATION: PROSPERO CRD42019140294.


Assuntos
Exercício/fisiologia , Infertilidade Masculina/epidemiologia , Reprodução/fisiologia , Espermatozoides/citologia , Adolescente , Adulto , Fragmentação do DNA , Feminino , Humanos , Nascimento Vivo/epidemiologia , Masculino , Pessoa de Meia-Idade , Gravidez , Taxa de Gravidez/tendências , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise do Sêmen/estatística & dados numéricos , Contagem de Espermatozoides/estatística & dados numéricos , Espermatozoides/metabolismo , Adulto Jovem
11.
Toxicol Lett ; 316: 60-72, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520699

RESUMO

Cholestasis is a significant decrease in bile flow. The liver is the primary organ affected by cholestasis. Chronic cholestasis could entail to tissue fibrotic changes and liver cirrhosis. Other organs, including heart, kidneys, nervous system, skeletal muscles, as well as the reproductive system, might also be affected during cholestasis. Although the cholestasis-associated pathological and biochemical alterations in organs such as liver have been widely investigated, there is little information about complications such as cholestasis-induced reproductive toxicity. The current study aimed to evaluate the pathologic effects of cholestasis on reproductive organs in both male and female animals. Rats underwent bile duct ligation (BDL) surgery. Markers of reproductive toxicity, including serum hormonal changes, tissue histopathological alterations, biomarkers of oxidative stress, and markers of mitochondrial impairment, were evaluated. Increased serum markers of liver injury and elevated level of cytotoxic molecules such as bile acids and bilirubin were evident in BDL animals. On the other hand, the serum level of hormones such as testosterone was suppressed in BDL rats. Significant histopathological alterations were also evident in the testis and ovary of BDL animals. A significant increase in oxidative stress markers, including ROS formation, lipid peroxidation, protein carbonylation, and depleted glutathione and antioxidant reservoirs were also detected in BDL rats. Moreover, mitochondrial depolarization decreased dehydrogenases activity, and depleted ATP content was detected in sperm isolated from the BDL group. These data indicate that cholestasis-associated reproductive toxicity in male and female rats is restrictedly coupled with severe oxidative stress and mitochondrial impairment.


Assuntos
Colestase/metabolismo , Mitocôndrias/metabolismo , Ovário/metabolismo , Estresse Oxidativo , Reprodução , Espermatozoides/metabolismo , Testículo/metabolismo , Animais , Colestase/etiologia , Colestase/fisiopatologia , Ducto Colédoco/cirurgia , Modelos Animais de Doenças , Feminino , Ligadura , Peroxidação de Lipídeos , Masculino , Mitocôndrias/patologia , Ovário/patologia , Ovário/fisiopatologia , Carbonilação Proteica , Ratos Sprague-Dawley , Medição de Risco , Testículo/patologia , Testículo/fisiopatologia
12.
Reprod Domest Anim ; 54 Suppl 3: 22-28, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31512320

RESUMO

The biological nature of age-related declines in fertility in males of any species, including stallions, has been elusive. In horses, the economic costs to the breeding industry are frequently extensive. Mitochondrial function in ejaculated sperm, which is essential for sperm motility, is reflected by adenosine triphosphate production, mitochondrial oxidative efficiency and production of reactive oxygen species, and that this balance may become compromised in ageing stallions and during the process of cryopreservation. This presentation will focus on mitochondrial integrity and function as an avenue for understanding the pathophysiology of sperm when undergoing cryopreservation and male ageing. We discuss the importance of understanding the differences and similarities of sperm mitochondria to that of somatic cells regarding structure and mitochondrial biochemistry relating to sperm function. The roles of oxidative phosphorylation and glycolysis in sperm mitochondria are outlined as is the method of determining oxygen consumption and calcium homoeostasis in sperm mitochondria. Further, we outline the role of oxidative stress and reactive oxygen species.


Assuntos
Cavalos/fisiologia , Mitocôndrias/fisiologia , Espermatozoides/fisiologia , Envelhecimento/fisiologia , Animais , Criopreservação/veterinária , Fertilidade/fisiologia , Glicólise , Masculino , Mitocôndrias/metabolismo , Fosforilação Oxidativa , Técnicas de Reprodução Assistida/veterinária , Motilidade Espermática/fisiologia , Espermatozoides/citologia , Espermatozoides/metabolismo
13.
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
14.
BMC Genomics ; 20(1): 714, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533629

RESUMO

BACKGROUND: Subfertility decreases the efficiency of the cattle industry because artificial insemination employs spermatozoa from a single bull to inseminate thousands of cows. Variation in bull fertility has been demonstrated even among those animals exhibiting normal sperm numbers, motility, and morphology. Despite advances in research, molecular and cellular mechanisms underlying the causes of low fertility in some bulls have not been fully elucidated. In this study, we investigated the metabolic profile of bull spermatozoa using non-targeted metabolomics. Statistical analysis and bioinformatic tools were employed to evaluate the metabolic profiles high and low fertility groups. Metabolic pathways associated with the sperm metabolome were also reported. RESULTS: A total of 22 distinct metabolites were detected in spermatozoa from bulls with high fertility (HF) or low fertility (LF) phenotype. The major metabolite classes of bovine sperm were organic acids/derivatives and fatty acids/conjugates. We demonstrated that the abundance ratios of five sperm metabolites were statistically different between HF and LF groups including gamma-aminobutyric acid (GABA), carbamate, benzoic acid, lactic acid, and palmitic acid. Metabolites with different abundances in HF and LF bulls had also VIP scores of greater than 1.5 and AUC- ROC curves of more than 80%. In addition, four metabolic pathways associated with differential metabolites namely alanine, aspartate and glutamate metabolism, ß-alanine metabolism, glycolysis or gluconeogenesis, and pyruvate metabolism were also explored. CONCLUSIONS: This is the first study aimed at ascertaining the metabolome of spermatozoa from bulls with different fertility phenotype using gas chromatography-mass spectrometry. We identified five metabolites in the two groups of sires and such molecules can be used, in the future, as key indicators of bull fertility.


Assuntos
Fertilidade , Metaboloma , Espermatozoides/metabolismo , Animais , Biomarcadores/metabolismo , Bovinos , Indústria de Laticínios , Masculino , Espermatozoides/citologia , Espermatozoides/fisiologia
15.
Chemosphere ; 234: 909-916, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31519099

RESUMO

T-2 toxin could impair male reproductive function. But, the toxicity mechanism is still unclear. In this study, male Kunming mice were orally administrated with T-2 toxin at the doses of 0, 0.5, 1 or 2 mg/kg body weight for 28 days. The fertility, body weight, reproductive organs volume, daily sperm production (DSP), and sperm malformation rate were detected. The expressions of testosterone (T) biosynthetic enzymes, luteinizing hormone (LH)-receptor, follicle stimulating hormone (FSH)-receptor and androgen binding protein (ABP) in testis were detected. The serum hormone level of gonadotropin-releasing hormone (GnRH), FSH, LH, T and progesterone (P), and the mRNA expression of GnRH, GnRH-receptor, LH and FSH were measured. These results demonstrated that T-2 toxin decreased body weight, reproductive organs volume and DSP, increased sperm malformation rate. T-2 toxin impaired fertility by decreasing the mating index, fertility index, numbers of implantation sites and viable fetuses, and increasing the number of animal with resorptions. Meantime, T-2 suppressed testicular function by inhibiting T biosynthesis and decreasing FSHR, LHR and ABP expression. Furthermore, the serum reproductive hormone contents and key factors expression of hypothalamic-pituitary-testis (HPT) axis were decreased by T-2 toxin. In summary, T-2 toxin impaired the male fertility by disrupting HPT axis and impairing testicular function.


Assuntos
Toxina T-2/toxicidade , Testículo/efeitos dos fármacos , Animais , Fertilidade , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Luteinizante/sangue , Masculino , Camundongos , Receptores do FSH/metabolismo , Receptores LHRH/metabolismo , Reprodução , Espermatozoides/metabolismo , Testículo/metabolismo , Testosterona/sangue
16.
Dev Genes Evol ; 229(5-6): 161-181, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31486889

RESUMO

KIF3A and KIF3B are homologous motor subunits of the Kinesin II protein family. KIF3A, KIF3B, and KAP3 form a heterotrimeric complex and play a significant role in spermatogenesis. Here, we first cloned full-length kif3a/3b cDNAs from Larimichthys polyactis. Lp-kif3a/3b are highly related to their homologs in other animals. The proteins are composed of three domains, an N-terminal head domain, a central stalk domain, and a C-terminus tail domain. Lp-kif3a/3b mRNAs were found to be ubiquitously expressed in the examined tissues, with high expression in the testis. Fluorescence in situ hybridization (FISH) was used to analyze the expression of Lp-kif3a/3b mRNAs during spermiogenesis. The results showed that Lp-kif3a/3b mRNAs had similar expression pattern and were continuously expressed during spermiogenesis. From middle spermatid to mature sperm, Lp-kif3a/3b mRNAs gradually localized to the side of the spermatid where the midpiece and tail form. In addition, we used immunofluorescence (IF) to observe that Lp-KIF3A protein co-localizes with tubulin during spermiogenesis. In early spermatid, Lp-KIF3A protein and microtubule signals were randomly distributed in the cytoplasm. In middle spermatid, however, the protein was detected primarily around the nucleus. In late spermatid, the protein migrated primarily to one side of the nucleus where the tail forms. In mature sperm, Lp-KIF3A and microtubules accumulated in the midpiece. Moreover, Lp-KIF3A co-localized with the mitochondria. In mature sperm, Lp-KIF3A and mitochondria were present in the midpiece. Therefore, Lp-KIF3A/KIF3B may be involved in spermiogenesis in L. polyactis, particularly during nuclear reshaping and tail formation.


Assuntos
Proteínas de Peixes/metabolismo , Peixes/fisiologia , Cinesina/metabolismo , Espermatogênese , Espermatozoides/citologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Núcleo Celular/metabolismo , Clonagem Molecular , Proteínas de Peixes/química , Proteínas de Peixes/genética , Humanos , Cinesina/química , Cinesina/genética , Masculino , Filogenia , Alinhamento de Sequência , Espermatozoides/metabolismo
17.
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
18.
Int J Mol Sci ; 20(18)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31514311

RESUMO

Hypogonadism and oxidative stress are occurring commonly in men with diabetes and associated male infertility. This study aimed to investigate the capability of anti-oxidative and anti-inflammatory properties of fucoxanthin as well as to evaluate its protective effects on male reproduction in diabetic rats. The RAW 264.7 macrophage cells were used to evaluate the anti-oxidative and anti-inflammatory activity. Thirty male Sprague-Dawley rats were induced by streptozotocin-nicotinamide for a diabetes model and fed either with three different doses of fucoxanthin (13, 26, and 65 mg/kg) or rosiglitazone (0.571 mg/kg) for four weeks. The fucoxanthin significantly inhibited nitric oxide production and reduced reactive oxygen species level in lipopolysaccharide-induced RAW 264.7 cells. In the animal study, fucoxanthin administration improved insulin resistance, restored sperm motility, decreased abnormal sperm number, and inhibited lipid peroxidation. Moreover, it restored GPR54 and SOCS-3 mRNA expression in the hypothalamus and recovered luteinizing hormone level, as well as the testosterone level. In conclusion, fucoxanthin not only possessed antioxidant and anti-inflammatory properties but also decreased the diabetes signs and symptoms as well as improved spermatogenesis and male reproductive function.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/fisiopatologia , Feófitas/química , Reprodução/efeitos dos fármacos , Xantofilas/uso terapêutico , Animais , Antioxidantes/metabolismo , Glicemia/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/induzido quimicamente , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Insulina/sangue , Resistência à Insulina , Kisspeptinas/genética , Kisspeptinas/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Niacinamida , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Células RAW 264.7 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Receptores de Kisspeptina-1/genética , Receptores de Kisspeptina-1/metabolismo , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Estreptozocina , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Testículo/efeitos dos fármacos , Testículo/patologia , Xantofilas/farmacologia
19.
Molecules ; 24(18)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31491847

RESUMO

Epicatechin (EPI) is a natural flavonoid with antibacterial, anti-inflammatory and anti-cancer properties. Furthermore, the molecule exhibits powerful reactive oxygen species (ROS) scavenging and metal-chelating properties. In this study, we assessed the efficiency of EPI to reverse ROS-mediated alterations to the motility, viability, DNA integrity and oxidative profile of bovine spermatozoa. For the first experiment, spermatozoa were washed out of fresh semen and exposed to 12.5 µmol/L EPI, 25 µmol/L EPI, 50 µmol/L EPI and 100 µmol/L EPI in the presence of ferrous ascorbate (FeAA) during a 6 h in vitro culture. For the second experiment, the ejaculates were split into aliquots and cryopreserved with a commercial semen extender supplemented with 12.5 µmol/L EPI, 25 µmol/L EPI, 50 µmol/L EPI, 100 µmol/L EPI or containing no supplement. Sperm motility was assessed using the computer-aided sperm analysis and the cell viability was studied with the metabolic activity test. ROS production was quantified using luminometry, and DNA fragmentation was evaluated using the chromatin dispersion test. Cell lysates were prepared at the end of the culture in order to assess the concentration of protein carbonyls and malondialdehyde. Exposure to FeAA led to a significantly reduced sperm motility (p < 0.001), mitochondrial activity (p < 0.001), but increased the generation of ROS (p < 0.001), as well as oxidative damage to proteins (p < 0.001), DNA (p < 0.001) and lipids (p < 0.001). EPI supplementation, particularly at a concentration range of 50-100 µmol/L, resulted in higher preservation of the spermatozoa vitality (p < 0.001). Furthermore, 50-100 µmol/L EPI were significantly effective in the prevention of oxidative damage to sperm proteins (p < 0.001), lipids (p < 0.001) and DNA (p < 0.01 in relation to 50 µmol/L EPI; p < 0.001 with respect to 100 µmol/L EPI). In the case of the cryopreserved spermatozoa, the administration of 50-100 µmol/L EPI resulted in higher sperm motility (p < 0.001) and mitochondrial activity (p < 0.001). ROS production, the number of protein carbonyls, lipid peroxidation as well as oxidative DNA damage were found to be significantly decreased particularly in samples cryopreserved in the presence of 100 µmol/L EPI (p < 0.001). Our results suggest that EPI could behave as an effective antioxidant which may prevent oxidative insults to spermatozoa, and thus, preserve their vitality and functionality. Nevertheless, its potential to achieve higher fertilization rates in reproductive technologies needs to be validated.


Assuntos
Antioxidantes/farmacologia , Catequina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Animais , Ácido Ascórbico/farmacologia , Bovinos , Fragmentação do DNA/efeitos dos fármacos , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Motilidade Espermática/efeitos dos fármacos
20.
Environ Pollut ; 254(Pt B): 113079, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31473390

RESUMO

Frequent exposure to arsenic is well documented to impair reproductive function in humans and animals. Biological significance of inorganic selenium and organoselenium, diphenyl diselenide (DPDS), has been attributed to their pharmacological activities. However, their roles in arsenic-mediated reproductive toxicity is lacking in literature. The present study evaluated the protective effects elicited by selenium and DPDS in arsenic-induced reproductive deficits in rats. Animals were either exposed to arsenic alone in drinking water at 60 µg AsO2Na L-1 or co-treated with selenium at 0.25 mg kg-1 or DPDS at 2.5 mg kg-1 body weight for 45 consecutive days. Results indicated that arsenic-mediated deficits in spermatogenic indices and marker enzymes of testicular function were significantly abrogated in rats co-treated with selenium or DPDS. Additionally, selenium or DPDS co-treatment prevented arsenic-mediated elevation in oxidative stress indices and significantly suppressed arsenic-mediated inflammation evidenced by diminished myeloperoxidase activity, nitric oxide, tumor necrosis factor alpha and interleukin-1 beta levels in hypothalamus, testes and epididymis of the rats. Moreover, selenium or DPDS abrogated arsenic mediated activation of caspase-3 activity and histological lesions in the treated rats. Taken together, selenium or DPDS improved reproductive function in arsenic-exposed rats via suppression of inflammation, oxidative stress and caspase-3 activation in rats.


Assuntos
Arsênico/toxicidade , Caspase 3/metabolismo , Inflamação/tratamento farmacológico , Selênio/administração & dosagem , Testículo/efeitos dos fármacos , Animais , Arsênico/metabolismo , Derivados de Benzeno/administração & dosagem , Caspase 3/genética , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Masculino , Compostos Organosselênicos/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espermatogênese/efeitos dos fármacos , Espermatozoides/citologia , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Testículo/imunologia , Testículo/metabolismo
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