Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 9.767
Filtrar
1.
Chemosphere ; 262: 127880, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32777607

RESUMO

BACKGROUND: Bisphenol A (BPA) is a well-known endocrine disruptor that affects male fertility. However, the main biological events through which BPA affects spermatogenesis remain to be identified. METHODS: Adult male mice were treated by feeding with drinking water containing BPA (0.2 µg/ml, 20 µg/ml, 200 µg/ml, respectively) for two months. Testes were collected for protein extraction or for immunohistochemical analysis. Epididymal spermatozoa were collected for sperm quality evaluation and male fertility assay by in vitro fertility (IVF). Serums were collected for detection of testosterone levels. Proteins associated with germ cell proliferation, meiosis, blood-testis barrier, and steroidogenesis production were examined in BPA-treated and control mice testes. CCK8 assay was used to detect the effect of BPA on the proliferation of GC-1 and GC-2 cells. RESULTS: The BPA-treated mice were characterized by decreased sperm quality, serum testosterone levels and, sub-fertile phenotype characterizing with low pregnancy rates and reduced fertilization efficiency. In lower BPA (0.2 µg/ml) treatment, PCNA and PLZF were down-expressed that indicated impaired germ cell proliferation. SYCP3 was down-expressed in BPA-treated mice, but expressions of other proteins associated with meiosis and blood-testis barrier were not significantly altered. CYP11A1 and HSD3B1 were down-expressed in BPA-treated mice that demonstrated reduced steroidogenesis activity. BPA has a concentration-dependent inhibition effect on the proliferation of GC-1 and GC-2 cells. Conclusively, low doses BPA exposure reduced mice sperm quality mainly by impairing germ cell proliferation, leading to reduced male fertility. The study would provide relevant information for investigation on molecular mechanisms and protective strategy on male production.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Fenóis/toxicidade , Espermatozoides/fisiologia , Animais , Proliferação de Células/efeitos dos fármacos , Disruptores Endócrinos/metabolismo , Epididimo/efeitos dos fármacos , Feminino , Fertilidade/efeitos dos fármacos , Masculino , Camundongos , Gravidez , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testes de Toxicidade Crônica
2.
Ecotoxicol Environ Saf ; 207: 111563, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254417

RESUMO

Exposure to endocrine-disrupting chemicals (EDCs) has been hypothesized as a cause of declining sheep reproductive efficiency. Understanding the long-term effects of EDCs such as heavy metals on reproductive health requires investigation in 'real life' of sheep that are reared in industrial areas. The aim of this study was to evaluate the effect of long-term exposure of Kermani rams to high levels of environmental heavy metals probably emitted from a copper smelter at KhatoonAbad in ShahreBabak, Kerman province. Testicular characteristics were determined in randomly-selected rams (3-4 years old) at 4 directions (south, north, east, and west) and 4 distances (10, 20, 30, and 40 km) from the smelter. Testicular trace element contents, size, serum testosterone, histological attributes and seminal characteristics, except semen volume, were affected by both the direction and the distance from the smelter (P < 0.05). Testicular contents of Pb, Cd, Cr, and Ni, and sperm abnormalities were higher at 10 km south from the smelter and lower at 40 km west. Other parameters were higher at 40 km west and lower at 10 km south. Interestingly, the testicular contents of Cu at 10 km south were lower and associated with higher sperm abnormalities in the rams reared closer to the smelter. The highest weight, length and circumference of the testis were found at 40 km west. The lowest concentration of testosterone was observed at 10 km south, being 92.6% lower than the highest values obtained at 40 km west. The diameter of seminiferous tubules and epithelial height at 10 km south were 8.9% and 27.5% lower than the highest values obtained at 40 km west. A positive correlation between Pb, Cd, Cr and Ni contents in the testis with sperm abnormalities, and a negative correlation between these elements with the other parameters were found. It was concluded that long-term exposure to heavy metals might have been a cause of decreased fertility in rams and probably other living species in this region.


Assuntos
Poluentes Ambientais/toxicidade , Metais Pesados/toxicidade , Testículo/efeitos dos fármacos , Animais , Cobre/toxicidade , Masculino , Reprodução , Análise do Sêmen/veterinária , Ovinos , Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Testículo/fisiologia , Testosterona/sangue , Testes de Toxicidade Crônica , Oligoelementos/metabolismo
3.
Chem Biol Interact ; 333: 109333, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33242462

RESUMO

Arsenic, a major environmental pollutant of global concern, is well-known for its reproductive toxicity. In this study, the protective potential of chlorogenic acid (CGA), a caffeoylquinic acid isomer abundantly found in many plants, was investigated against sodium arsenite (NaAsO2)-induced testicular dysfunctions. Adult male Swiss mice were either administered NaAsO2 alone at 5 mg kg-1 or co-treated with CGA at 100 mg kg-1 or 200 mg kg-1 body weight for 4 weeks. Results showed that NaAsO2-treated mice exhibited marked declines in testes weight, sperm count, and viability accompanied by decreases in sexual hormonal levels. Moreover, NaAsO2 toxicity evoked exhaustion of antioxidant markers (SOD, CAT, GPx, GR, and GSH), down-regulation of Nrf2 (nuclear factor erythroid 2-related factor 2) gene expression level, and elevations in malondialdehyde. Further, elevations in inflammatory cytokines (IL-1, TNF-α, and IL-6) together with the up-regulation of pro-apoptotic biomarkers (Bax and caspase- 3) and down-regulation of anti-apoptotic Bcl-2 were observed in NaAsO2 intoxication. Immunohistochemical analysis of testis sections of NaAsO2-treated mice showed high caspase-3 expression. These findings were well supported with testicular histopathological examination. However, pretreatment of mice with CGA resulted in noteworthy improvements in testicular damage induced by arsenic in a dose-dependent manner possibly mediated by the Nrf2 signaling pathway. Conclusively, CGA counteracted arsenic-induced testicular injury through its antioxidant, anti-inflammatory, and anti-apoptotic properties. Therefore, CGA could serve as a favorable intervention in the alleviation of arsenic-induced reproductive toxicity.


Assuntos
Apoptose/efeitos dos fármacos , Arsênico/toxicidade , Ácido Clorogênico/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/fisiopatologia , Animais , Antioxidantes/metabolismo , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Contagem de Espermatozoides , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Testículo/metabolismo , Testículo/patologia
4.
Ecotoxicol Environ Saf ; 208: 111476, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33091778

RESUMO

Male fertility is linked with several well-orchestrated events including spermatogenesis, epididymal maturation, capacitation, the acrosome reaction, fertilization, and beyond. However, the detrimental effects of bisphenol A (BPA) on sperm maturation compared to spermatogenesis and sperm cells remain unclear. Therefore, this study was to investigate whether pubertal exposure to BPA induces male infertility via interruption of the immune response in the epididymis. CD-1 male mice (5 weeks old) were treated daily with vehicle (corn oil) and 50 mg BPA/kg-BW for 6 weeks by oral gavage. Following BPA exposure, we observed decreased intraepithelial projection of basal cells, indicative of changes to the luminal environment. We also observed decreased projection of macrophages and protrusion of apoptotic cells into the lumen induced by incomplete phagocytosis of apoptotic cells in the caput epididymis. Exposure to BPA also reduced the anti- and pro-inflammatory cytokines IL-10, IL-6, IFN-γ, and IL-7 in the epididymis, while the chemotaxis-associated cytokines CCL12, CCL17, CXCL16, and MCP-1 increased. This study suggests two possible mechanisms for BPA induction of male infertility. First, exposure to BPA may induce an imbalance of immune homeostasis by disrupting the ability of basal cells to perceive environmental changes. Second, exposure to BPA may lead to collapse of macrophage phagocytosis via downregulation of intraepithelial projection and inflammatory-related cytokines. In conclusion, the observed potential pathways can lead to autoimmune disorders such epididymitis and orchitis.


Assuntos
Compostos Benzidrílicos/toxicidade , Epididimo/efeitos dos fármacos , Substâncias Perigosas/toxicidade , Fenóis/toxicidade , Animais , Epididimo/metabolismo , Humanos , Infertilidade Masculina , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos
5.
PLoS One ; 15(12): e0239380, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33326428

RESUMO

Atrazine is a common agricultural herbicide previously shown to promote epigenetic transgenerational inheritance of disease to subsequent generations. The current study was designed as an epigenome-wide association study (EWAS) to identify transgenerational sperm disease associated differential DNA methylation regions (DMRs) and differential histone retention regions (DHRs). Gestating female F0 generation rats were transiently exposed to atrazine during the period of embryonic gonadal sex determination, and then subsequent F1, F2, and F3 generations obtained in the absence of any continued exposure. The transgenerational F3 generation males were assessed for disease and sperm collected for epigenetic analysis. Pathology was observed in pubertal onset and for testis disease, prostate disease, kidney disease, lean pathology, and multiple disease. For these pathologies, sufficient numbers of individual males with only a single specific disease were identified. The sperm DNA and chromatin were isolated from adult one-year animals with the specific diseases and analyzed for DMRs with methylated DNA immunoprecipitation (MeDIP) sequencing and DHRs with histone chromatin immunoprecipitation (ChIP) sequencing. Transgenerational F3 generation males with or without disease were compared to identify the disease specific epimutation biomarkers. All pathologies were found to have disease specific DMRs and DHRs which were found to predominantly be distinct for each disease. No common DMRs or DHRs were found among all the pathologies. Epimutation gene associations were identified and found to correlate to previously known disease linked genes. This is one of the first observations of potential sperm disease biomarkers for histone retention sites. Although further studies with expanded animal numbers are required, the current study provides evidence the EWAS analysis is effective for the identification of potential pathology epimutation biomarkers for disease susceptibility.


Assuntos
Atrazina/efeitos adversos , Biomarcadores/metabolismo , Metilação de DNA/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Epigenoma/genética , Histonas/genética , Espermatozoides/efeitos dos fármacos , Animais , Metilação de DNA/genética , Doença/genética , Suscetibilidade a Doenças , Epigênese Genética/genética , Epigenômica/métodos , Feminino , Predisposição Genética para Doença/genética , Herbicidas/farmacologia , Hereditariedade/efeitos dos fármacos , Hereditariedade/genética , Histonas/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Espermatozoides/metabolismo
6.
Chem Biol Interact ; 332: 109303, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33132140

RESUMO

The present study aims to explore the effects of astaxanthin on the semen quality of diabetes mellitus (DM) KKAy mice. A total of 60 DM KKAy mice with similar body weights and initial blood glucose and serum lipid levels were assigned to four groups, namely, one control and three astaxanthin treatments (10, 50, or 100 mg/kg astaxanthin). Results show that oral astaxanthin administration reduced fasting blood glucose and serum total cholesterol, low-density lipoprotein cholesterol, insulin and nitrate oxide levels in the testis of DM KKAy mice. Astaxanthin also improved the high-density lipoprotein cholesterol, protein and superoxide dismutase levels in the testis; serum interleukin-11, tumour necrosis factor-α and interferon-γ levels; and sperm density, sperm movement and normal morphology rate of DM KKAy mice. Based on the results, astaxanthin can effectively affect serum cytokines and ameliorate semen quality of DM KKAy mice; thus, it may be developed as an adjuvant drug to treat diabetes mellitus-induced infertility.


Assuntos
Citocinas/sangue , Diabetes Mellitus Experimental/sangue , Sêmen/metabolismo , Animais , Glicemia/metabolismo , Insulina/sangue , Lipídeos/sangue , Masculino , Camundongos , Óxido Nítrico/metabolismo , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Superóxido Dismutase/metabolismo , Testículo/metabolismo , Xantofilas/farmacologia
7.
Biomed Environ Sci ; 33(10): 760-770, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33228835

RESUMO

Objective: This research was performed to evaluate the effect of tebuconazole (TBZ) on reproductive organs of male rats and to assess the protective role of combined essential trace elements in alleviating the detrimental effect of TBZ on male reproductive function. Methods: For this purpose, 48 rats were exposed to 100 mg/kg TBZ, TBZ supplemented with zinc (Zn), selenium (Se), copper (Cu), and iron (Fe), TBZ + (Se + Zn); TBZ + Cu; or TBZ + Fe. The experiment was conducted for 30 consecutive days. Results: TBZ caused a significant perturbation in mineral levels and reduction in reproductive organs weights, plasma testosterone level, and testicular antioxidant enzyme activities. The TBZ-treated group also showed a significant increase in sperm abnormalities (count, motility, and viability percent), plasma follicle-stimulating hormone and luteinizing hormone concentrations, lipid peroxidation, protein oxidation, and severe DNA degradation in comparison with the controls. Histopathologically, TBZ caused testis impairments. Conversely, treatment with trace elements, in combination or alone, improved the reproductive organ weights, sperm characteristics, TBZ-induced toxicity, and histopathological modifications in testis. Conclusion: TBZ exerts significant harmful effects on male reproductive system. The concurrent administration of trace elements reduces testis dysfunction, fertility, and toxicity induced by TBZ.


Assuntos
Antioxidantes/metabolismo , Fungicidas Industriais/efeitos adversos , Minerais/metabolismo , Espermatozoides/fisiologia , Testículo/efeitos dos fármacos , Oligoelementos/metabolismo , Triazóis/efeitos adversos , Ração Animal/análise , Animais , Dieta , Suplementos Nutricionais/análise , Masculino , Testes de Mutagenicidade , Ratos , Ratos Wistar , Espermatozoides/efeitos dos fármacos , Testículo/fisiologia , Oligoelementos/administração & dosagem
8.
Toxicol Appl Pharmacol ; 408: 115274, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33038357

RESUMO

Greater understanding of the efficiency of nanoparticles will assist future research related to male reproductive performance. The current study was performed to assess the potency of selenium nanoparticles (SeNPs) in alleviating deltamethrin (DLM)-induced detrimental effects on sperm characteristics, oxidative status, sexual behavior, and the histological structure of the testes and epididymis in male rats. Thirty-two male Wister rats were divided into four groups according to treatment received orally by gavage 3 times/week for 60 days; control, DLM (0.6 mg/kg bwt), SeNPs (0.5 mg/kg bwt), and DLM-SeNPs groups. DLM caused a significant reduction in sperm count, motility, and viability percent, as well as in body weight and serum testosterone level, blood total antioxidant capacity (TAC), and glutathione peroxidase (GPx) activity. The DLM-treated group showed a significant increase in blood malondialdehyde (MDA) concentration and sperm abnormalities (%), as well as a significant reduction in sexual activity, manifested as an increase in mount, intromission, or ejaculation latency and a reduction in mount or intromission frequency. These toxic effects were confirmed by histological alterations, represented by a significant reduction in the diameter of the seminiferous tubules and spermatogenesis. Conversely, treatment with SeNPs improved DLM-induced negative effects on sperm characteristics, testosterone, and antioxidant biomarkers, as well as behavioral and histopathological alterations. The SeNPs treated group showed improved semen parameters, antioxidant status, and sexual performance. In conclusion, SeNPs may represent an effective treatment for reducing the detrimental effects of DLM on male fertility, and lead to enhanced male reproductive performance.


Assuntos
Inseticidas/toxicidade , Nanopartículas/administração & dosagem , Nitrilos/toxicidade , Piretrinas/toxicidade , Reprodução/efeitos dos fármacos , Selênio/administração & dosagem , Animais , Feminino , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Comportamento Sexual Animal/efeitos dos fármacos , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/patologia , Testosterona/sangue
9.
PLoS One ; 15(10): e0241105, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33119667

RESUMO

The aim of our study was to examine the effects of crocin (0.5 (C0.5), 1 (C1) and 1.5 (C1.5) mM) and naringenin (50 (N50), 100 (N100) and 150 (N150) µM) in cryopreservation extender for freezing rooster semen. Sperm motility, viability, abnormalities, membrane functionality, active mitochondria, apoptosis status, lipid peroxidation (LP), GPX, SOD, TAC, the mRNA expression of pro-apoptotic (CASPASE 3) and anti-apoptotic (Bcl-2) genes, fertile eggs, hatched eggs and hatching rate were investigated following freeze-thawing. C1 and N100 resulted in higher (P < 0.05) total motility and progressive motility in comparison to the control group. The C1 and N100 groups improved viability, membrane functionality and reduced lipid peroxidation. We found higher values for active mitochondria with C1 and N100 compared to control group. The C1 and N100 groups showed lower percentages of early apoptosis when compared with control group. Also, C1 and N100 had higher TAC, compared to the control group. The mRNA expressions of BCL-2 in the C1 and N100 groups were significantly higher than that of other treatments. The expression of CASPASES 3 was significantly reduced in C1 and N100 group (P < 0.05) when compared to control group. Significantly higher percentages of fertile eggs, hatched eggs and hatching rate were observed in C1 and N100 compared to the control group. In conclusion, crocin at 1 mM and naringenin at 100 µM seem to improve the post-thawing rooster semen quality, fertility and could protect the sperm by reducing the pro-apoptotic (CASPASE 3) and increasing anti-apoptotic (Bcl-2) genes.


Assuntos
Carotenoides/farmacologia , Crioprotetores/farmacologia , Flavanonas/farmacologia , Preservação do Sêmen/veterinária , Sêmen/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Galinhas , Criopreservação/métodos , Criopreservação/veterinária , Fertilidade/efeitos dos fármacos , Masculino , Preservação do Sêmen/métodos , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/citologia
10.
Medicine (Baltimore) ; 99(43): e22662, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120757

RESUMO

BACKGROUND: The reproductive dilemma faced by men has always been the focus of the whole society. Idiopathic asthenozoospermia (AZS), as one of the common causes of male infertility, lack of specific treatment. Traditional Chinese medicine has shown potential benefits in the management of male infertility. Yishentongluo decoction (YSTL) is a representative Chinese herbal formula; however, there is still no rigorous clinical trial supporting its application. Therefore, we designed a randomized controlled trial to evaluate the efficacy and safety of YSTL for patients with idiopathic AZS and explain the possible action mechanisms of YSTL in improving sperm motility. METHODS: In this randomized controlled study, a total of 160 eligible patients will be assigned to YSTL group or the Levocarnitine oral solution group in a 1:1 ratio. The treatment period will be 12 weeks and the follow-up period will last 4 weeks. The primary outcome will be the the progressive (motility), sperm rate (%). Secondary outcomes will include the progressive (motility) + non-progressive (motility) sperm rate(%), total effective sperm count, inner mitochondrial membrane potential (MMP) in spermatozoa, and spouse pregnancy rate (%). Safety outcomes will cover electrocardiogram , blood tests (including blood routine test, hepatic function, and renal function), urine routine test, and stool routine test. The semen parameters, sperm MMP test, and all the safety outcomes will be performed at the baseline, 4th, 8th and 12th week. The pregnancy outcome will be evaluated at 4 weeks after treatment. DISCUSSION: This study will provide initial evidence regarding the efficacy and safety of YSTL in the treatment of idiopathic AZS with kidney deficiency and blood stasis pattern. In addition, potential mechanisms of YSTL in improving sperm motility will be explored based on sperm MMP test. TRIAL REGISTRATION: Chinese Clinical Trials Register identifier, ChiCTR2000033290, registered on 26 May 2020.


Assuntos
Astenozoospermia/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Masculino , Medicina Tradicional Chinesa , Ensaios Clínicos Controlados Aleatórios como Assunto , Espermatozoides/efeitos dos fármacos
11.
Mutat Res ; 821: 111722, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32920458

RESUMO

DNA damage is a common feature of human spermatozoa associated with an impaired capacity to fertilize the oocyte and an increased mutational load in the offspring. However, the etiology of this damage remains poorly defined. In this study we demonstrate that a major pathway for the induction of DNA damage in mammalian spermatozoa is triggered by exposure to exogenous cell free DNA (cfDNA). Exposure of human and mouse spermatozoa to cfDNA (calf thymus, mouse liver and salmon testes) in vitro induced a dose-dependent increase in sperm DNA damage that could be effectively suppressed by the concomitant presence of DNase. The induction of such damage was not accompanied by any concomitant change in sperm motility or vitality and was not directly associated with the induction of oxidative stress. In vivo the injection of exogenous DNA again precipitated an increase in sperm DNA fragmentation that could be reversed by the prior administration of DNase. Similarly, the induction of a transient unilateral testicular ischemia induced an increase in DNA fragmentation that was evident within 24 h and sustained for at least 14 days via mechanisms that could be completely suppressed by the prior administration of DNase. We conclude that exogenous cfDNA activates a defensive response in human spermatozoa associated with the nuclease-mediated induction of DNA fragmentation, possibly involving the participation of TLR9 and CD4. These novel insights have significant implications for our understanding of DNA fragmentation in the male germ line and open up new pathways for the remediation of this condition.


Assuntos
Ácidos Nucleicos Livres/farmacologia , Dano ao DNA , Fertilidade/efeitos dos fármacos , Estresse Oxidativo , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/patologia , Animais , Feminino , Humanos , Masculino , Camundongos , Espermatozoides/efeitos dos fármacos
12.
Toxicol Appl Pharmacol ; 408: 115253, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32991915

RESUMO

Exposure to arsenic, which occurs via various routes, can cause reproductive toxicity. However, the mechanism for arsenic-induced reproductive disorders in male mice has not been extensively investigated. Here, 6-week-old male mice were dosed to 0, 5, 10, or 20 ppm sodium arsenite (NaAsO2), an active form of arsenic, in drinking water for six months. For male mice exposed to arsenite, fertility was lower compared to control mice. Moreover, for exposed mice, there were lower sperm counts, lower sperm motility, and higher sperm malformation ratios. Further, the mRNA and protein levels of the gonadotropin-regulated testicular RNA helicase (DDX25) and chromosome region maintenance-1 protein (CRM1), along with proteins associated with high mobility group box 2 (HMGB2), phosphoglycerate kinase 2 (PGK2), and testicular angiotensin-converting enzyme (tACE) were lower. Furthermore, chronic exposure to arsenite led to lower H2A ubiquitination (ubH2A); histone H3 acetylation K18 (H3AcK18); and histone H4 acetylations K5, K8, K12, and K16 (H4tetraAck) in haploid spermatids from testicular tissues. These alterations disrupted deposition of protamine 1 (Prm1) in testes. Overall, the present results indicate that the ubiquitination and acetylation of histones is involved in the spermiogenesis disorders caused by chronic exposure to arsenite, which points to a previously unknown connection between the modification of histones and arsenite-induced male reproductive toxicity.


Assuntos
Arsenitos/toxicidade , Histonas/metabolismo , Reprodução/efeitos dos fármacos , Acetilação/efeitos dos fármacos , Animais , Feminino , Reabsorção do Feto , Masculino , Troca Materno-Fetal , Camundongos Endogâmicos C57BL , Gravidez , Análise do Sêmen , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/anormalidades , Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Testículo/anormalidades , Testículo/efeitos dos fármacos , Ubiquitinação/efeitos dos fármacos
13.
Sci Rep ; 10(1): 16022, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32994467

RESUMO

Men consume the most nicotine and cannabis products but impacts on sperm epigenetics are poorly characterized. Evidence suggests that preconception exposure to these drugs alters offspring neurodevelopment. Epigenetics may in part facilitate heritability. We therefore compared effects of exposure to tetrahydrocannabinol (THC) and nicotine on DNA methylation in rat sperm at genes involved in neurodevelopment. Reduced representation bisulfite sequencing data from sperm of rats exposed to THC via oral gavage showed that seven neurodevelopmentally active genes were significantly differentially methylated versus controls. Pyrosequencing data revealed majority overlap in differential methylation in sperm from rats exposed to THC via injection as well as those exposed to nicotine. Neurodevelopmental genes including autism candidates are vulnerable to environmental exposures and common features may mediate this vulnerability. We discovered that autism candidate genes are significantly enriched for bivalent chromatin structure, suggesting this configuration may increase vulnerability of genes in sperm to disrupted methylation.


Assuntos
Metilação de DNA/efeitos dos fármacos , Dronabinol/efeitos adversos , Redes Reguladoras de Genes/efeitos dos fármacos , Nicotina/efeitos adversos , Espermatozoides/química , Animais , Transtorno Autístico/genética , Cromatina/química , Cromatina/efeitos dos fármacos , Cromatina/genética , Ilhas de CpG/efeitos dos fármacos , Modelos Animais de Doenças , Epigênese Genética/efeitos dos fármacos , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , Ratos , Análise de Sequência de DNA , Espermatozoides/efeitos dos fármacos
14.
Sci Rep ; 10(1): 15269, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943691

RESUMO

Green tea is a popularly consumed beverage worldwide and contains polyphenols, whose antioxidant activities could improve sperm parameters and fertility thereof. We investigated the effect of green tea on the male rat reproductive system as well as its safety. Male Wistar rats were administered 2 and 5% aqueous extract of green tea for 52 days' ad libitum, while the control group received tap water. Total polyphenol, flavanol, flavonol and soluble solids significantly increased in a concentration-dependent manner in vitro (P < 0.01). Weights of body, testis, epididymis, prostate gland, seminal vesicles, and liver, serum levels of testosterone, ferric reducing antioxidant power, creatinine, and sperm motility, remained unchanged (P > 0.05). Kidney weight, sperm concentration and vitality, spontaneous acrosome reaction increased (P < 0.05), while alanine transaminase and aspartate transaminase levels decreased (P < 0.05). Catalase, superoxide dismutase, glutathione and lipid peroxidation remained unchanged in the testes, liver and kidney (P > 0.05). Histological sections of testis, epididymis, kidney and liver showed no conspicuous alteration. Diameter and epithelial height of seminiferous tubule decreased, while caudal epididymis epithelial height increased (P < 0.01). Consumption of green tea in the conditions used in the present study seems to be safe and improved sperm parameters. However, subtle structural changes observed in the decreased diameter and epithelial height of the seminiferous tubule and increased acrosome reaction needs further investigation.


Assuntos
Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Reprodução/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Chá/química , Reação Acrossômica/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Catalase/metabolismo , Epididimo/efeitos dos fármacos , Epididimo/metabolismo , Rim/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/metabolismo , Contagem de Espermatozoides/métodos , Motilidade Espermática/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/metabolismo , Superóxido Dismutase/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo
15.
J Med Life ; 13(2): 138-143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32742504

RESUMO

Treatment with anticancer drugs such as cyclophosphamide can harm the male reproductive system. Vitamin C and zinc are micronutrients with antioxidant activity and are the essential components of semen. Therefore, this study aimed to evaluate whether cyclophosphamide-exposed mice can recover from fertility with vitamin C and zinc therapy. In this experimental study, fifty male mice were divided into five groups. Groups 1-4 received cyclophosphamide (100 mg/kg, once a week for eight weeks). Also, group 2 received zinc (200 mg/kg), group 3 received vitamin C (300 mg/kg), group 4 received zinc and vitamin C (200 mg/kg and 300 mg/kg, respectively), five times per week for eight weeks, and group 5 received normal saline once a week and water five days a week for eight weeks. The data collected were statistically analyzed using SPSS 22. Results showed a significant increase in mount latency and a significant decrease in the number of sperms in the cyclophosphamide group compared to the control group. However, mount latency has been significantly decreased in mice treated with cyclophosphamide plus zinc compared to the cyclophosphamide group. The study also showed that the sperm count in the group that received cyclophosphamide and zinc had been increased compared to the cyclophosphamide group; the other treatments have decreased mount latency and increased the sperm count compared to the group treated with cyclophosphamide but not significantly. The Tubule Differentiation Index showed an increase in the cyclophosphamide-Zinc-Vitamin C group in comparison with the cyclophosphamide group. The current study showed that zinc could improve cyclophosphamide-induced toxicity of the reproductive system in male mice.


Assuntos
Antineoplásicos/efeitos adversos , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Substâncias Protetoras/farmacologia , Reprodução/efeitos dos fármacos , Zinco/farmacologia , Animais , Ácido Ascórbico/administração & dosagem , Ciclofosfamida/efeitos adversos , Hormônios/metabolismo , Humanos , Masculino , Camundongos , Comportamento Sexual Animal/efeitos dos fármacos , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos
16.
Sci Rep ; 10(1): 13118, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32753627

RESUMO

Sperm cell motility and morphology observed under the bright field microscopy are the only criteria for selecting a particular sperm cell during Intracytoplasmic Sperm Injection (ICSI) procedure of Assisted Reproductive Technology (ART). Several factors such as oxidative stress, cryopreservation, heat, smoking and alcohol consumption, are negatively associated with the quality of sperm cell and fertilization potential due to the changing of subcellular structures and functions which are overlooked. However, bright field imaging contrast is insufficient to distinguish tiniest morphological cell features that might influence the fertilizing ability of sperm cell. We developed a partially spatially coherent digital holographic microscope (PSC-DHM) for quantitative phase imaging (QPI) in order to distinguish normal sperm cells from sperm cells under different stress conditions such as cryopreservation, exposure to hydrogen peroxide and ethanol. Phase maps of total 10,163 sperm cells (2,400 control cells, 2,750 spermatozoa after cryopreservation, 2,515 and 2,498 cells under hydrogen peroxide and ethanol respectively) are reconstructed using the data acquired from the PSC-DHM system. Total of seven feedforward deep neural networks (DNN) are employed for the classification of the phase maps for normal and stress affected sperm cells. When validated against the test dataset, the DNN provided an average sensitivity, specificity and accuracy of 85.5%, 94.7% and 85.6%, respectively. The current QPI + DNN framework is applicable for further improving ICSI procedure and the diagnostic efficiency for the classification of semen quality in regard to their fertilization potential and other biomedical applications in general.


Assuntos
Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos , Microscopia , Estresse Oxidativo , Razão Sinal-Ruído , Espermatozoides/citologia , Espermatozoides/metabolismo , Criopreservação , Etanol/farmacologia , Humanos , Peróxido de Hidrogênio/farmacologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos
17.
Nanotoxicology ; 14(8): 1039-1057, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32813582

RESUMO

Oysters are keystone species that use external fertilization as a sexual mode. The gametes are planktonic and face a wide range of stressors, including plastic litter. Nanoplastics are of increasing concern because their size allows pronounced interactions with biological membranes, making them a potential hazard to marine life. In the present study, oyster spermatozoa were exposed for 1 h to various doses (from 0.1 to 25 µg mL-1) of 50-nm polystyrene beads with amine (50-NH2 beads) or carboxyl (50-COOH beads) functions. Microscopy revealed adhesion of particles to the spermatozoa membranes, but no translocation of either particle type into cells. Nevertheless, the 50-NH2 beads at 10 µg mL-1 induced a high spermiotoxicity, characterized by a decrease in the percentage of motile spermatozoa (-79%) and in the velocity (-62%) compared to control spermatozoa, with an overall drop in embryogenesis success (-59%). This major reproduction failure could be linked to a homeostasis disruption in exposed spermatozoa. The 50-COOH beads hampered spermatozoa motility only when administered at 25 µg mL-1 and caused a decrease in the percentage of motile spermatozoa (-66%) and in the velocity (-38%), but did not affect embryogenesis success. Microscopy analyses indicated these effects were probably due to physical blockages by microscale aggregates formed by the 50-COOH beads in seawater. This toxicological study emphasizes that oyster spermatozoa are a useful and sensitive model for (i) deciphering the fine interactions underpinning nanoplastic toxicity and (ii) evaluating adverse effects of plastic nanoparticles on marine biota while waiting for their concentration to be known in the environment.


Assuntos
Crassostrea/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Nanopartículas/toxicidade , Poliestirenos/toxicidade , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Masculino , Reprodução/efeitos dos fármacos , Espermatozoides/patologia
18.
Life Sci ; 258: 118192, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32781062

RESUMO

The present study was conducted to identify possible health - promoting effects of wogonin (Wog) on testicular dysfunction in rats caused by cadmium. Pre-treatment of cadmium chloride (Cd: 5 mg/kg b.wt.) administered rats with wogonin (10 mg/kg b.wt) resulted in significant improvement in Cd-induced decrease in body and organ (testes and epididymides) weights. Wogonin treatment significantly improved Cd-induced reduction in sperm quality and quantity, steroidogenic gene (SFI, StAR, CYP11A1, 3ß-HSD, CYP17A1 and 17ß-HSD) and protein (SF1, StAR and CYP17A1) expressions and serum testosterone levels. Wogonin treatment provided significant protection to Cd-induced aggression in testicular oxidative (elevated levels of MDA) and anti-oxidative (diminished activities of SOD, CAT and GPx) status. Wog significantly up-regulated mRNA levels of Nrf2, NQO1 and HO-1 and down-regulation of Keap1 in cadmium treated testes. Wogonin administration significantly suppressed Cd-stimulated increase in inflammatory reactions (increase in NF-κB p65 DNA, p-IKKß, TNF-α levels and decrease in IL-10 levels). Wogonin prevented apoptotic damage by enhanced protein distribution of caspase-9, caspase-3, and Bax due to Cd exposure. Furthermore, Wogonin presented significant protection to histo-morphometric changes resulted after Cd administration. Taken together, the findings of this study provided clear evidence of the therapeutic potential of Cd-induced testicular toxicity at least partly due to its antioxidant, anti-inflammatory and anti-apoptotic properties.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Cádmio/toxicidade , Flavanonas/farmacologia , Substâncias Protetoras/farmacologia , Transdução de Sinais , Testículo/patologia , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Ingestão de Líquidos/efeitos dos fármacos , Epididimo/efeitos dos fármacos , Epididimo/patologia , Comportamento Alimentar/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônios/sangue , Inflamação/patologia , Masculino , Oxirredução , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Esteroides/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo
19.
Toxicology ; 442: 152556, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32758512

RESUMO

The reproductive toxicity associated with furan exposure in both animals and humans has been documented. Protocatechuic acid (PCA), a dietary polyphenolic chemical, reportedly elicits beneficial effects on the male reproductive system. However, the influence of PCA on the reproductive toxicity related to furan exposure is unavailable in the literature. The current study evaluated the effects of PCA on the dysfunctional reproductive axis caused by furan exposure in rats. Experimental animals were exposed to furan (8 mg/kg) or co-treated with furan (8 mg/kg) and PCA (25 or 50 mg/kg) for twenty-eight successive days. Results revealed that PCA treatment significantly alleviated furan-mediated declines in sperm production and characteristic qualities as well as in serum levels of prolactin, luteinizing hormone, follicle-stimulating hormone, and testosterone. Further, PCA attenuated furan-induced reduction in antioxidant enzyme activities and testicular function marker enzymes, namely lactate dehydrogenase, glucose-6-phosphate dehydrogenase, acid phosphatase, and alkaline phosphatase. PCA effectively mitigated furan-mediated increases in myeloperoxidase activity, levels of reactive oxygen and nitrogen species, nitric oxide, tumour necrosis factor-alpha, and interleukin-1ß in testes, epididymis, and hypothalamus of rats. Moreover, PCA increased anti-inflammatory cytokine interleukin-10 but suppressed caspase-9 and caspase-3 activities and ameliorated injuries in the testes, epididymis, and hypothalamus of furan-treated rats. In conclusion, PCA ameliorated deficits in the hypothalamic-pituitary-gonadal axis function in furan-exposed rats by suppressing oxido-inflammatory stress and apoptosis.


Assuntos
Furanos , Hidroxibenzoatos/uso terapêutico , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/tratamento farmacológico , Animais , Antioxidantes/metabolismo , Citocinas/metabolismo , Hormônios/sangue , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Masculino , Hipófise/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Reprodução/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/enzimologia , Testículo/metabolismo
20.
Aquat Toxicol ; 226: 105580, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32712368

RESUMO

Bisphenol A (BPA), a well-known estrogenic endocrine disruptor, is ubiquitously present in the environment, possessing the potential to interfere with the reproductive endocrine system in male mammals. However, there are limited studies on the reproductive toxicity in male aquatic animals associated with epigenetic modifications. In order to evaluate the potential effects of BPA on reproduction and better understand the underlying mechanism, adult male rare minnow (Gobiocypris rarus) were exposed to 15 µg L-1 BPA over a period of 63 d. Results showed that BPA induced congestion of blood vessels and infiltration of inflammatory cells after 21 d exposure, and decreased sperm fertilization after 63 d exposure. The genome DNA methylation levels were significantly increased throughout the treatment, and a strong positive stain were found in the spermatocyte, spermatid and sperm. The H3K4me3 level in all types of germ cell were increased by 21 d exposure while decreased following 63 d exposure. The positive stain of H3K9me3 was decreased in sperms while increased in spermatids by 21 d exposure. In addition, the H3K9me3 level was significantly increased after 63 d exposure, and a strong positive stain were found in spermatocytes, spermatids, and sperms. Our result also revealed that the transcripts of DNA methyltransferase genes (dnmt1 and dnmt3-8) and histone methyltransferase genes (mll2-5, setdb1-2 and ezh2) were also markedly changed under BPA exposure for 21-63 d. These findings indicated that BPA had toxicity in male reproductive, and DNA/histone methylation might play a vital role in the regulation of BPA-triggered the decreased of sperm quality.


Assuntos
Compostos Benzidrílicos/toxicidade , Cyprinidae/metabolismo , Metilação de DNA/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Histonas/metabolismo , Fenóis/toxicidade , Espermatozoides/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , DNA/metabolismo , Feminino , Humanos , Masculino , Análise do Sêmen , Espermatozoides/metabolismo , Testículo/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA