RESUMO
PURPOSE: Varicocele is a condition known to cause damage to seminal parameters and sperm function. Furthermore, it has been hypothesized that the varicocele effect on fertility is time-dependent; however, little is known about the consequences of its establishment time on reproductive organs and/or sperm function. This study aimed to evaluate the effect of the duration of experimental varicocele on reproductive organs, sperm parameters, and sperm function. MATERIALS AND METHODS: Varicocele induction surgeries were performed in Wistar rats aged 40 or 100 days old. At 160-day-old, analyses were performed, including biometry of reproductive organs (prostate, seminal vesicles, epididymis, and testis), sperm parameters (vitality, morphology, and motility), and sperm function tests (nuclear DNA integrity, acrosome integrity, and mitochondrial activity). RESULTS: The analysis of the biometry of reproductive organs showed no differences between distinct ages in which varicocele was induced. The total abnormal sperm morphology was bigger in animals with varicocele induced to 100 days old than in animals with varicocele induced to 40 days old. Regarding nuclear DNA integrity, animals of varicocele induced to 100 days old showed worse results compared to animals of varicocele induced to 40 days old. Other parameters analyzed showed no differences between varicocele groups. CONCLUSION: In this study conducted on rats, we conclude that varicocele adversely affects sperm, particularly its function. However, we did not observe a negative progressive effect on sperm.
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Ratos Wistar , Análise do Sêmen , Motilidade dos Espermatozoides , Espermatozoides , Varicocele , Animais , Masculino , Varicocele/fisiopatologia , Varicocele/patologia , Espermatozoides/fisiologia , Motilidade dos Espermatozoides/fisiologia , Fatores de Tempo , Modelos Animais de Doenças , Testículo/patologia , Ratos , Fatores Etários , Epididimo/patologiaRESUMO
INTRODUCTION: Spermatozoa are highly specialized cells with unique morphology. In addition, spermatozoa lose a considerable amount of cytoplasm during spermiogenesis, when they also compact their DNA, resulting in a transcriptionally quiescent cell. Throughout the male reproductive tract, sperm will acquire proteins that enable them to interact with the female reproductive tract. After ejaculation, proteins undergo post-translational modifications for sperm to capacitate, hyperactivate, and fertilize the oocyte. Many proteins have been identified as predictors of male infertility and also investigated in diseases that compromise reproductive potential. AREAS COVERED: In this review, we proposed to summarize the recent findings about the sperm proteome and how they affect sperm structure, function, and fertility. A literature search was performed using PubMed and Google Scholar databases within the past 5 years until August 2022. EXPERT OPINION: Sperm function depends on protein abundance, conformation, and PTMs; understanding the sperm proteome may help to identify pathways essential to fertility, even making it possible to unravel the mechanisms involved in idiopathic infertility. In addition, proteomics evaluation offers knowledge regarding alterations that compromise the male reproductive potential.
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Infertilidade Masculina , Proteoma , Humanos , Masculino , Feminino , Proteoma/metabolismo , Sêmen/metabolismo , Espermatozoides/metabolismo , Fertilidade/genética , Infertilidade Masculina/genéticaRESUMO
Testicular torsion (TT) is an emergency complication that leads to oxidative stress and adversely affects spermatogenesis. Although immediate treatment consists of testicular detorsion (TD) to reverse TT-induced ischemia, mechanisms underlying recovery have yet to be fully understood. The current study aimed to investigate TD effects after a one-hour experimental TT by evaluating testicular antioxidant status and apoptosis-related proteins. Forty male Wistar rats were submitted to TT by testicular rotation, for one hour. Following TT, 32 rats were submitted to TD for 1, 2, 4, and 8 h (N = 8/group), the other 8 rats euthanized as TT-only. For controls, 8 rats were sham-operated. Testicular tissues were aseptically dissected for biochemical, histopathological, and immunohistochemistry analyses. The TD groups, especially after 4 h of TD, exhibited diminished MDA and increased TAC and GPX levels in testicular tissue. Levels of p53 and Caspase-3 were down-regulated in T1D4 and T1D8 groups versus torsion group. Bcl-2 was increased in T1D4 and T1D8 groups compared to the TT group. Moreover, spermatogenesis was recovered in T1D4 and T1D8 groups compared to the TT group. It can be concluded that after 1 h TT in rats, at least 4 h post-TD is needed for testicular tissue to initiate recovery.
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Traumatismo por Reperfusão , Torção do Cordão Espermático , Animais , Antioxidantes/metabolismo , Antioxidantes/uso terapêutico , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/patologia , Torção do Cordão Espermático/patologia , Testículo/patologiaRESUMO
Infertility is a worldwide issue impacting 15% of couples' population. Male-related infertility results in almost 50% of these cases. Considering lifestyle factors associated with infertility, here in this literature review article, we aimed to discuss training/sport effects on male-related infertility. Regarding this issue, human and animal model studies related to the subject were gathered and analysed. Exercise is well known as a general improving factor, however, excessive exercise can result in male infertility due to reduced hypothalamus-pituitary-gonadal axis (HPT) function, increased oxidative stress and chronic inflammation. Consequently, these underlying impacts result in a low testosterone production, and reduced semen quality, and can lead to infertility. In contrast, it has been revealed that exercise can improve male fertility status in lifestyle-induced infertility condition such as obesity and diabetes. Indeed, exercise, by increasing testicular antioxidant defence, reducing pro-inflammatory cytokines level and enhancing the steroidogenesis process, leads to improved spermatogenesis and semen quality in lifestyle-induced infertility. In fact, it seems that individual health status as well as exercise volume, intensity and duration are effective-involved co-factors that influence the impact that exercise will promote on male fertility. Regarding these findings, it is important to study exercise different impacts in further clinical trials in order to generate preservative guidelines for exercise and also considering exercise as a treatment option in lifestyle-induced disease management.
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Infertilidade Masculina , Análise do Sêmen , Exercício Físico , Fertilidade , Humanos , Infertilidade Masculina/etiologia , Masculino , EspermatogêneseRESUMO
INTRODUCTION: Azoospermia, absence of sperm in the ejaculate is classified as obstructive (OA) and non-obstructive azoospermia (NOA). In OA, sperm are produced, but due to physical obstruction in the male reproductive tract, they are not released in the ejaculate. NOA, on the other hand, is defined as the absence of sperm in the ejaculate due to testicular dysfunction. In NOA, spermatogenesis is frequently preserved in specific sites, and proteomics studies have been employed in order to identify men with preserved spermatogenesis. AREAS COVERED: Differential protein expression in patients with male infertility is an indicator of impaired spermatogenesis. Here, we reviewed proteins with a potential role as biomarkers of spermatogenesis that could help in the management of non-obstructive and obstructive azoospermia. The following keywords were used for bibliographic research: seminal plasma, proteomics, male infertility, nonobstructive, obstructive, azoospermia, oligospermia. EXPERT OPINION: Biopsy is an invasive and potentially harmful technique for detecting spermatogenesis in men with OA and NOA. Seminal plasma proteins are highly promising as biomarkers for spermatogenesis. Current literature presents a number of potential candidate biomarkers for determining preserved spermatogenesis.
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Azoospermia , Biomarcadores , Humanos , Masculino , Sêmen , Espermatogênese , EspermatozoidesRESUMO
PURPOSE: Sperm DNA fragmentation is a major cellular mechanism underlying varicocele-related male infertility. However, the type of DNA fragmentation - whether oxidative or of another nature - remains unknown. Thus, the aim of this study was to evaluate single- and double-stranded sperm DNA fragmentation, and oxidative-induced sperm DNA damage in men with varicocele. MATERIALS AND METHODS: A cross-sectional study was performed, including 94 normozoospermic adults, of which 39 men without varicocele (controls) and 55 men with varicocele grades II or III, uni- or bilaterally. All men collected semen by masturbation. After semen analysis, the remaining volume was used for evaluation of three types of sperm DNA damage: (i) total DNA fragmentation, using an alkaline comet assay, (ii) double-stranded DNA fragmentation, using a neutral comet assay, and (iii) oxidative DNA damage, using an alkaline comet assay associated with the DNA glycosylase formamidopyrimidine enzyme. In each assay, percentage of sperm with any degree of DNA fragmentation, and with high DNA fragmentation were compared between the groups using an unpaired Student's t test or a Mann-Whitney test. RESULTS: The varicocele group presented a higher rate of sperm with fragmented DNA (both any and high DNA fragmentation), considering single-stranded DNA fragmentation, double-stranded DNA fragmentation, or a combination of both, as well as oxidative-induced DNA fragmentation. CONCLUSIONS: Patients with varicocele have an increase in sperm DNA fragmentation levels, particularly in oxidative stress-induced sperm DNA damage.
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Infertilidade Masculina , Varicocele , Adulto , Estudos Transversais , Fragmentação do DNA , Humanos , Infertilidade Masculina/genética , Masculino , Estresse Oxidativo , Motilidade dos Espermatozoides , Espermatozoides , Varicocele/genéticaRESUMO
The aim of this article was to evaluate the effects of different concentrations of carnosine added during human semen processing. Semen samples from 34 patients were submitted to processing by discontinuous density gradient centrifugation without (control) or with different concentrations of carnosine supplementation as follows: (a) 20 mM of carnosine supplementation on the layers of Percoll; and (b) 50 mM carnosine supplementation. Sperm samples were then washed with human tubal fluid medium and evaluated according to sperm kinetics and functional assessment. For statistical analysis, data were evaluated by a general linear model or a Friedman test, whenever appropriate. The 50 mM carnosine supplementation led to improved sperm mitochondrial activity when compared to untreated samples. Motility variables, such as percentage of motile and progressively motile spermatozoa, average path velocity, straight line velocity, curvilinear velocity and linearity, showed an improvement after semen processing irrespective of carnosine supplementation. Both concentrations of carnosine increased the beat-cross frequency (BCF) when compared to samples before processing. We conclude that carnosine supplementation in semen samples benefits sperm mitochondrial activity and BCF.
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Carnosina/farmacologia , Espermatozoides/efeitos dos fármacos , Adulto , Fragmentação do DNA/efeitos dos fármacos , Humanos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Pessoa de Meia-Idade , Estudos Prospectivos , Análise do Sêmen , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Superóxidos/metabolismo , Adulto JovemRESUMO
Seminal plasma proteins already demonstrated to reflect the testicular environment function and important regulatory mechanisms. However, it is crucial to understand which of these proteins participate in probable altered pathways in testicular germ cell tumours and after unilateral orchiectomy. In this study, we proposed to verify, by a multiplex approach, the levels of DNA damage and apoptosis pathways' proteins, in seminal plasma of men before and after unilateral orchiectomy, and also in control men. Comparing pre- and post-orchiectomy groups, just the apoptosis pathways' proteins presented different levels, in which Bad was lower and Bcl2, Akt, caspase-9, p53 and caspase-8 were higher after orchiectomy. When comparing pre- and post-orchiectomy groups with control, both presented lower levels of ChK1, Chk2, H2AX, p53 and p21, for DNA damage pathway. Regarding the apoptosis pathway, lower levels of JNK, Bcl2, Akt, caspase-9, p53 and caspase-8 and higher levels of Bad were observed before orchiectomy. The post-orchiectomy group did not differ from controls, demonstrating a probable restoration on its proteins levels. We can conclude that testicular tumours can alter both of the assessed pathways, and its removal is associated with a probable restoration of the apoptosis pathway.
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Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Apoptose , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/cirurgia , Orquiectomia , Sêmen , Neoplasias Testiculares/cirurgiaRESUMO
Introduction: The seminal proteome has been shown to directly influence the male fertile potential. Post-translational modifications (PTMs) are significant changes that play a role in the biological regulation of proteins. Sperm cells are transcriptionally and translationally inactive and these modifications are essential to control protein function.Areas covered: Here we reviewed seven PTMs which importance for male reproductive function investigated in the past decade, namely S-nitrosylation and tyrosine nitration (both occurring by the action of NO), glycosylation, ubiquitination, acetylation, methylation, and SUMOylation. Since they were previously identified in human semen, we focus on their role in sperm function, as well as in physiological and pathophysiological processes which could contribute to the fertility potential. The following keywords were applied: 'post-translational modification', 'sperm', 'semen', 'seminal plasma', 'male infertility', 'nitrosylation', 'nitration', 'histone methylation', 'SUMOylation', 'ubiquitination', 'ubiquitilation', 'glycosylation', and 'acetylation'.Expert opinion: Most biological processes orchestrated by proteins require PTMs for their activation or inhibition. Most of them are dynamic and occur in mature sperm, modulating protein function, thus exerting a significant role in sperm function and fertility. Finally, the study of PTMs should be also addressed in pathophysiological processes, as different clinical conditions are known to alter the proteome.
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Fertilidade/genética , Infertilidade Masculina/genética , Proteoma/genética , Sêmen/metabolismo , Acetilação , Glicosilação , Humanos , Infertilidade Masculina/patologia , Masculino , Processamento de Proteína Pós-Traducional/genética , Espermatozoides/metabolismo , Espermatozoides/patologia , Ubiquitinação/genéticaRESUMO
The study of male infertility after spinal cord injury (SCI) has enhanced the understanding of seminal plasma (SP) as an important regulator of spermatozoa function. However, the most important factors leading to the diminished sperm motility and viability observed in semen of men with SCI remained unknown. Thus, to explore SP related molecular mechanisms underlying infertility after SCI, we used mass spectrometry-based quantitative proteomics to compare SP retrieved from SCI patients to normal controls. As a result, we present an in-depth characterization of the human SP proteome, identifying â¼2,800 individual proteins, and describe, in detail, the differential proteome observed in SCI. Our analysis demonstrates that a hyper-activation of the immune system may influence some seminal processes, which likely are not triggered by microbial infection. Moreover, we show evidence of an important prostate gland functional failure,i.e.diminished abundance of metabolic enzymes related to ATP turnover and those secreted via prostasomes. Further we identify the main outcome related to this fact and that it is intrinsically linked to the low sperm motility in SCI. Together, our data highlights the molecular pathways hindering fertility in SCI and shed new light on other causes of male infertility.
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Infertilidade Masculina/etiologia , Infertilidade Masculina/metabolismo , Proteoma/metabolismo , Proteômica/métodos , Traumatismos da Medula Espinal/complicações , Adulto , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Espectrometria de Massas/métodos , Pessoa de Meia-Idade , Sêmen/metabolismo , Motilidade dos Espermatozoides , Traumatismos da Medula Espinal/metabolismoRESUMO
PURPOSE: To determine enzymatic antioxidant and lipid peroxidation levels in seminal plasma of patients orchiectomized for testicular tumors. MATERIALS AND METHODS: The study included 52 patients: 26 control men and 26 orchiectomized patients for testicular tumor, of which 12 men had seminoma tumor and 14 men non-seminoma tumor. After semen analysis performed according to the WHO guidelines, an aliquot of semen was centrifuged and the seminal plasma was collected. Lipid peroxidation was performed by thiobarbituric acid reactive substances(TBARS) assay and antioxidant profile was assessed by analyzing catalase, glutathione per-oxidase (GPx) and superoxide anion (SOD) activities using colorimetric assays with a standard spectrophotometer. Data were tested for normality and compared using one-way ANOVA (p<0.05). RESULTS: Seminoma and non-seminoma groups presented lower sperm concentration and morphology when compared to control group (p=0.0001). Both study groups (seminoma and non-seminoma) presented higher TBARS levels when compared to control group (p=0.0000013). No differences were observed for SOD (p=0.646) and GPx (p=0.328). It was not possible to access the enzymatic activity of catalase in any group. CONCLUSION: Patients with testicular tumor present increased semen oxidative stress, but no differences were observed in antioxidant levels, even after orchiectomy. This indicates that most likely an increased generation of oxidative products takes place in these patients.
Assuntos
Antioxidantes/metabolismo , Peroxidação de Lipídeos/fisiologia , Sêmen/enzimologia , Seminoma/metabolismo , Neoplasias Testiculares/metabolismo , Adolescente , Adulto , Estudos de Casos e Controles , Catalase/metabolismo , Estudos Transversais , Glutationa Peroxidase/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Oligospermia , Orquiectomia , Estresse Oxidativo/fisiologia , Análise do Sêmen , Contagem de Espermatozoides , Superóxido Dismutase/metabolismo , Neoplasias Testiculares/cirurgia , Adulto JovemRESUMO
Spermatozoa are unique cells that have highly compact DNA, motility (and hypermotility) patterns, a specific morphology, localized mitochondria and an apical acrosome. They are the end product of a dynamic process termed spermatogenesis. Sperm are therefore produced with specific proteins in order to effect different traits, such as the presence of cysteine-rich protamines in DNA, which effectively compacts DNA. Moreover, specific proteins are transferred during epididymal maturation and after ejaculation in order to render sperm capable of undergoing post-ejaculatory alterations, generally termed capacitation, which confers capacity to fertilize a mature oocyte. In addition, sperm exhibit several post-translational modifications, which are fundamental to their function, such as SUMOylation and ubiquitination. Discussed in this review is the current knowledge of the sperm proteome in terms of its composition and the function that these proteins determine, as well as their post-translational modifications and how these alter sperm functional integrity. Studies are emphasized that focus on shotgun proteomics--untargeted determination of the protein constituent of a cell in a given biological condition--and technologies currently applied toward that end are reviewed.
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Infertilidade Masculina/metabolismo , Terapia de Alvo Molecular/métodos , Proteoma/metabolismo , Proteômica/métodos , Espermatozoides/metabolismo , Animais , Humanos , Infertilidade Masculina/tratamento farmacológico , Masculino , Processamento de Proteína Pós-TraducionalRESUMO
OBJECTIVE: To evaluate the effect of smoking on sperm functional quality and seminal plasma proteomic profile. PATIENTS AND METHODS: Sperm functional tests were performed in 20 non-smoking men with normal semen quality, according to the World Health Organization (2010) and in 20 smoking patients. These included: evaluation of DNA fragmentation by alkaline Comet assay; analysis of mitochondrial activity using DAB staining; and acrosomal integrity evaluation by PNA binding. The remaining semen was centrifuged and seminal plasma was used for proteomic analysis (liquid chromatography-tandem mass spectrometry). The quantified proteins were used for Venn diagram construction in Cytoscape 3.2.1 software, using the PINA4MS plug-in. Then, differentially expressed proteins were used for functional enrichment analysis of Gene Ontology categories, Kyoto Encyclopedia of Genes and Genomes and Reactome, using Cytoscape software and the ClueGO 2.2.0 plug-in. RESULTS: Smokers had a higher percentage of sperm DNA damage (Comet classes III and IV; P < 0.01), partially and fully inactive mitochondria (DAB classes III and IV; P = 0.001 and P = 0.006, respectively) and non-intact acrosomes (P < 0.01) when compared with the control group. With respect to proteomic analysis, 422 proteins were identified and quantified, of which one protein was absent, 27 proteins were under-represented and six proteins were over-represented in smokers. Functional enrichment analysis showed the enrichment of antigen processing and presentation, positive regulation of prostaglandin secretion involved in immune response, protein kinase A signalling and arachidonic acid secretion, complement activation, regulation of the cytokine-mediated signalling pathway and regulation of acute inflammatory response in the study group (smokers). CONCLUSION: In conclusion, cigarette smoking was associated with an inflammatory state in the accessory glands and in the testis, as shown by enriched proteomic pathways. This state causes an alteration in sperm functional quality, which is characterized by decreased acrosome integrity and mitochondrial activity, as well as by increased nuclear DNA fragmentation.
Assuntos
Proteômica , Análise do Sêmen/métodos , Sêmen/fisiologia , Proteínas de Plasma Seminal/análise , Fumar/fisiopatologia , Espermatozoides/fisiologia , Acrossomo , Adulto , Estudos Transversais , Fragmentação do DNA , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/fisiologia , Adulto JovemRESUMO
PURPOSE: To verify if the presence of varicocele (grades II and III) with and without seminal alterations, using the 5th centile cutoff values in table A1.1 of the World Health Organization (WHO, 2010) manual, alters the seminal plasma levels of proteins DNASE1 (deoxyribonuclease-1) and IGFBP7 (Insulin-like growth factor-binding protein 7), which are related to apoptosis regulation and cell proliferation, respectively, demonstrating that these proteins are important for correct spermatogenesis. METHODS: This cross sectional study was performed at the Sao Paulo Federal University Paulo between May 2014 and April 2016. A total of 61 male adolescents were included in this study, of which 20 controls without varicocele (C), 22 with varicocele and normal semen analysis (VNS) and 19 with varicocele and altered semen analysis (VAS). Seminal plasma from each patient was used for Western blotting analysis of individual protein levels. Values of each protein were normalized to a testicular housekeeping protein (PARK7-protein deglycase DJ-1). RESULTS: Levels of IGFBP7 protein are increased in varicocele. Levels of DNASE1 are progressively decreased in varicocele (lower in varicocele and normal semen analysis, lowest in varicocele and altered semen analysis) when compared to adolescents without varicocele. DNASE1 levels are positively correlated with sperm concentration and morphology (correlation values of 0.400 and 0.404, respectively; p values of 0.001 and 0.001, respectively). CONCLUSION: In conclusion, in adolescents, seminal plasma levels of IGFBP7, responsible for proliferative activity, are increased in varicocele grades II and III, and DNASE1, responsible for apoptosis regulation, are lower in varicocele, lowest in varicocele and low semen quality. These proteins demonstrate molecular alterations brought upon by varicocele. Moreover, DNASE1 is capable of discriminating a varicocele that causes alterations to semen quality from one that does not. We propose that the initial response of varicocele is to increase proliferative activity which, if followed by regulation of apoptosis, may lead to the ejaculation of a population of sperm that are in accordance with WHO cutoff values but, in the presence of dysregulated apoptosis, leads to lower sperm concentration and morphology.
Assuntos
Infertilidade Masculina/genética , Espermatogênese , Espermatozoides/patologia , Varicocele/genética , Adolescente , Adulto , Apoptose/genética , Proliferação de Células/genética , Humanos , Infertilidade Masculina/patologia , Masculino , Sêmen/fisiologia , Contagem de Espermatozoides , Motilidade dos Espermatozoides/fisiologia , Varicocele/patologiaRESUMO
The impact of diabetes on various organs failure including testis has been highlighted during the last decades. If on one hand diabetes-induced hyperglycemia has a key role in induced damages; on the other hand, glucose deprivation plays a key role in inducing male infertility. Indeed, glucose metabolism during spermatogenesis has been highlighted due to post-meiotic germ cells drastic dependence on glucose-derived metabolites, especially lactate. In fact, hyperglycemia-induced spermatogenesis arrest has been demonstrated in various studies. Moreover, various sperm maturation processes related to sperm function such as motility are directly depending on glucose metabolism in Sertoli cells. It has been demonstrated that diabetes-induced hyperglycemia adversely impacts sperm morphology, motility and DNA integrity, leading to infertility. However, fertility quality is another important factor to be considered. Diabetes-induced hyperglycemia is not only impacting sperm functions, but also affecting sperm epigenome. DNA packing process and epigenetics modifications occur during spermatogenesis process, determining next generation genetic quality transmitted through sperm. Critical damages may occur due to under- or downregulation of key proteins during spermatogenesis. Consequently, unpacked DNA is more exposed to oxidative stress, leading to intensive DNA damages. Moreover, epigenetic dysregulation occurred during spermatogenesis may impact embryo quality and be transmitted to next generations, increasing offspring genetic issues. Herein we discuss the mechanisms by which diabetes-induced hyperglycemia can affect epigenetic modifications and DNA packaging and methylation during spermatogenesis thus promoting long-lasting effects to the next generation.
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Traumatic brain injury (TBI) is a prevalent and debilitating condition, which often leads to the development of post-traumatic epilepsy (PTE), a condition that yet lacks preventive strategies. Biperiden, an anticholinergic drug, is a promising candidate that has shown efficacy in murine models of PTE. MicroRNAs (miRNAs), small regulatory RNAs, can help in understanding the biological basis of PTE and act as TBI- and PTE-relevant biomarkers that can be detected peripherally, as they are present in extracellular vesicles (EVs) that cross the blood-brain barrier. This study aimed to investigate miRNAs in serum EVs from patients with TBI, and their association with biperiden treatment and PTE. Blood samples of 37 TBI patients were collected 10 days after trauma and treatment initiation in a double-blind clinical trial. A total of 18 patients received biperiden, with three subjects developing PTE, and 19 received placebo, with two developing PTE. Serum EVs were characterized by size distribution and protein profiling, followed by high-throughput sequencing of the EV miRNome. Differential expression analysis revealed no significant differences in miRNA expression between TBI patients with and without PTE. Interestingly, miR-9-5p displayed decreased expression in biperiden-treated patients compared to the placebo group. This miRNA regulates genes enriched in stress response pathways, including axonogenesis and neuronal death, relevant to both PTE and TBI. These findings indicate that biperiden may alter miR-9-5p expression in serum EVs, which may play a role in TBI resolution.
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Endometriosis is a gynecological disease that affects women of reproductive age. The protein profiles of women with endometriosis who were able or unable to achieve pregnancy and women without endometriosis who did achieve pregnancy were compared in this study. The follicular fluid was collected from 21 patients undergoing in vitro-fertilization treatment, according to the following groups: nine women in the control group (Group C), four women with endometriosis who achieved pregnancy (Group E.P), and eight women with endometriosis who did not achieve pregnancy (Group E.NP). Follicular fluid proteins were separated using 2D-electrophoresis, and their spots were compared, excised, and submitted to LC-ESI-MS/MS for proteins identification. The analysis showed 29 differentially expressed spots among the groups, and from these, 21 proteins were identified. Analysis showed some functional enrichment in the E.P group, including response to oxidative stress and apoptosis, while the E.NP group showed functions related to response to reactive oxygen species and positive regulation of apoptosis. These data suggest that endometriosis leads to differential protein expression in the follicular fluid, which can influences the outcome of pregnancy. These proteins may be potential targets for better diagnostics and new therapeutic intervention in affected women, as well as assisting in comprehending the physiopathologic mechanisms underlying endometriosis.
Assuntos
Endometriose/metabolismo , Líquido Folicular/química , Proteoma/análise , Adulto , Biomarcadores/análise , Biomarcadores/química , Estudos de Casos e Controles , Eletroforese em Gel Bidimensional , Feminino , Fertilização in vitro , Humanos , Infertilidade Feminina/metabolismo , Gravidez , Proteoma/metabolismo , Proteômica/métodosRESUMO
BACKGROUND: Varicocele is one of the main causes of male infertility. Although the pathophysiology mechanism of varicocele is very well described and understood, there are some unanswered questions that remains unknown. Some studies have previously described the state of testicular inflammation and sperm in animal models, especially the mouse model, and the seminal plasma of men with varicocele, with or without changes in semen parameters. METHODS OF STUDY: This review intended to verify the role of inflammatory mechanism in varicocele, using clinical studies as well as animal model studies on the effect of inflammation caused by varicocele on the function of testicular somatic and germ cells. RESULTS: In-vivo studies confirmed whether anti-inflammatory molecules could treat the semen of men with varicocele and rats with varicocele. The use of different anti-inflammatory agents in mouse model studies provided a new perspective for future clinical studies to investigate the effect of concurrent treatment with surgery to improve surgical outcomes. CONCLUSION: Similar to animal model studies, previously conducted clinical trials have demonstrated the effectiveness of anti-inflammatory therapy in varicocele patients. However, clinical trials using anti-inflammatory are needed to be conducted agents to evaluate different aspects of this therapeutical approach in varicocele patients.
Assuntos
Infertilidade Masculina , Varicocele , Humanos , Camundongos , Masculino , Animais , Ratos , Sêmen , Espermatozoides , Infertilidade Masculina/etiologia , Inflamação/complicações , Anti-Inflamatórios/uso terapêutico , Motilidade dos EspermatozoidesRESUMO
BACKGROUND: Testicular torsion is a condition in which a testis rotates around its longitudinal axis and twists the spermatic cord. This in turn results in a significant decrease in blood flow and perfusion of testicular tissue. During Testicular torsion, the testicular tissue is affected by ischemia, heat stress, hypoxia, and oxidative and nitrosative stress. The testicular torsion should be considered an emergency condition and surgical intervention (testicular detorsion ) as the sole treatment option in viable cases involves counter-rotation on twisted testes associated, when possible, to orchipexy, in order to avoid recurrence. Possible testicular detorsion side-effects occur due to reperfusion and endothelial cells injury, microcirculation disturbances, and intense germ cells loss. OBJECTIVES: To discuss testicular torsion surgery-based methods, different time frames for testicular torsion induction, and the associated pathophysiology by emphasizing cellular and molecular events as well as different therapeutic agent applications for testicular torsion. MATERIALS AND METHODS: We reviewed all original research and epidemiological papers related to testicular torsion condition. RESULTS: Testicular torsion causes germ cell necrosis, arrested spermatogenesis, and diminished testosterone levels, with consequent infertility. Among different involved pathophysiological impacts, testicular torsion/detorsion-induced ischemia seems to play the key role by leading the tissue toward other series of events in testis. Numerous studies have used adjuvant antioxidants, calcium channel blockers, anti-inflammatory agents, or vasodilating agents in order to decrease these effects. DISCUSSION AND CONCLUSION: To the best of our knowledge, no previously conducted study examined therapeutical agents' beneficial effects post clinical I/R condition in humans. Different agents targeting different pathophysiological conditions were used to ameliorate the ischemia/reperfusion-induced condition in animal models, however, none of the administrated agents were tested in human cases. Although considering testicular detorsion surgery is still the golden method to reverse the testicular torsion condition and the surgical approach is undeniable, the evaluated agents with beneficial effects, need to be investigated furthermore in clinical conditions. Thus, furthermore clinical studies and case reports are required to approve the animal models proposed agents' beneficial impacts.
Assuntos
Traumatismo por Reperfusão , Torção do Cordão Espermático , Ratos , Masculino , Animais , Humanos , Torção do Cordão Espermático/complicações , Células Endoteliais , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , TestículoRESUMO
OBJECTIVE: To evaluate the effect of chronic sleep deprivation on sperm function quality in mice. DESIGN: Experimental study. SETTING: Not applicable. ANIMALS: Spermatozoa from twenty-four 10-week-old C57BL/6J male mice. INTERVENTION(S): The sleep deprivation group underwent gentle handling for 6 hours for 5 consecutive days. The mice in the sleep recovery group were allowed to sleep during the 24-hour period after the sleep deprivation protocol. MAIN OUTCOME MEASURE(S): After euthanasia, the spermatozoa were collected for analysis. Sperm motility was evaluated using computer-assisted sperm analyzer. Intracellular superoxide anion (O2-) activity, acrosome integrity, mitochondrial activity, and DNA fragmentation assays were conducted afterward. RESULT(S): Sleep deprivation and sleep recovery groups presented a lower percentage of spermatozoa with an intact acrosome, compared with the respective control groups. Regarding DNA fragmentation, a decreased proportion of spermatozoa with Comet I class intact DNA was observed in the sleep recovery group, compared with the recovery control group. Beat cross frequency was increased in the sleep recovery group. CONCLUSION(S): Sleep deprivation can reduce sperm quality, impairing acrosome integrity. Sleep recovery decreased DNA integrity and increased beat cross frequency.