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1.
Medicine (Baltimore) ; 99(38): e21960, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957313

RESUMO

INTRODUCTION: Sperm DNA integrity has been considered as one of the important determinants of normal fertilization and embryonic development in natural and assisted pregnancy. It is difficult for men with high levels of sperm DNA fragmentation (SDF) in semen to conceive their partners naturally and assist in conception. The studies have found that the level of SDF in the semen of patients with varicocele (VC) was on the high side. In recent years, the effect of VC surgery on DNA fragmentation index has attracted the attention of researchers. In this study, we will evaluate the effectiveness of VC repair as a way to alleviate SDF and improve male fertility. METHODS AND ANALYSIS: Electronic databases including English databases (PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library) and Chinese databases (China National Knowledge Infrastructure, China Biology Medicine Database, Wanfang Database, VIP Database) will be searched from their inception to December 2020 to recognize related studies. All the randomized controlled trials of microsurgical varicocelectomy for the management of VC patients will be included. The potential outcome will include improvement in SDF, oxidative stress markers (reactive oxygen species, nitric oxide, and lipid peroxidation products), sperm chromatin compaction, other advanced sperm function characteristics, follow-up of fertility results. We will conduct this study strictly according to the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: The study is a protocol for systematic review and meta-analysis without results, and data analysis will be carried out after the protocol. We will share our findings on April 5th of 2021. CONCLUSION: This systematic review will provide more evidence to assess whether varicocelectomy is an effective intervention for patients with SDF. The results will be published in a public issue journal and offer the urologists help to make clinical decisions. ETHICS AND DISSEMINATION: Formal ethical approval is not required in this protocol. We will collect and analyze data based on published research. Since this research does not involve patients, personal privacy will not be affected. The results of this review will be distributed to peer-reviewed journals or submitted to relevant conferences. PROTOCOL REGISTRATION NUMBER: INPLASY202070119.


Assuntos
Fragmentação do DNA , Espermatozoides/patologia , Varicocele/cirurgia , Cromatina/metabolismo , Humanos , Masculino , Estresse Oxidativo/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
2.
PLoS Genet ; 16(8): e1008954, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32785227

RESUMO

The flagellum is essential for sperm motility and fertilization in vivo. The axoneme is the main component of the flagella, extending through its entire length. An axoneme is comprised of two central microtubules surrounded by nine doublets, the nexin-dynein regulatory complex, radial spokes, and dynein arms. Failure to properly assemble components of the axoneme in a sperm flagellum, leads to fertility alterations. To understand this process in detail, we have defined the function of an uncharacterized gene, Cfap97 domain containing 1 (Cfap97d1). This gene is evolutionarily conserved in mammals and multiple other species, including Chlamydomonas. We have used two independently generated Cfap97d1 knockout mouse models to study the gene function in vivo. Cfap97d1 is exclusively expressed in testes starting from post-natal day 20 and continuing throughout adulthood. Deletion of the Cfap97d1 gene in both mouse models leads to sperm motility defects (asthenozoospermia) and male subfertility. In vitro fertilization (IVF) of cumulus-intact oocytes with Cfap97d1 deficient sperm yielded few embryos whereas IVF with zona pellucida-free oocytes resulted in embryo numbers comparable to that of the control. Knockout spermatozoa showed abnormal motility characterized by frequent stalling in the anti-hook position. Uniquely, Cfap97d1 loss caused a phenotype associated with axonemal doublet heterogeneity linked with frequent loss of the fourth doublet in the sperm stored in the epididymis. This study demonstrates that Cfap97d1 is required for sperm flagellum ultra-structure maintenance, thereby playing a critical role in sperm function and male fertility in mice.


Assuntos
Axonema/genética , Proteínas do Citoesqueleto/genética , Dineínas/genética , Infertilidade Masculina/genética , Animais , Chlamydomonas/genética , Cílios/genética , Cílios/patologia , Fertilização In Vitro , Humanos , Infertilidade Masculina/patologia , Masculino , Camundongos , Camundongos Knockout , Motilidade Espermática/genética , Cauda do Espermatozoide/metabolismo , Cauda do Espermatozoide/patologia , Espermatozoides/crescimento & desenvolvimento , Espermatozoides/patologia , Testículo/crescimento & desenvolvimento , Testículo/patologia
3.
Med Hypotheses ; 143: 110083, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32679425

RESUMO

The outbreak of CoronaVirus Disease19 (COVID19) in December 2019 posed a serious threat to public safety, and its rapid spread caused a global health emergency. Clinical data show that in addition to respiratory system damage, some male patients with COVID-19 are also accompanied by abnormal renal function and even renal damage. As the main receptor of syndrome coronavirus 2 (SARS-CoV-2), angiotensin converting enzyme 2 (ACE2) is also found to be highly expressed not only in respiratory mucosa and alveolar epithelial cells, but also in renal tubule cells, testicular Leydig cells and seminiferous tubule cells. This suggests that SARS-CoV-2 has the possibility of infecting the male reproductive system, and the recent detection of SARS-CoV-2 in the patient's semen further confirms this theory. In previous studies, it has been found that ACE2 has the ability to regulate autophagy. Not only that, recent studies have also found that SARS-CoV-2 infection can also lead to a reduction in autophagy. All of these associate SARS-CoV-2 with autophagy. Furthermore, autophagy has been shown to have an effect on male reproduction in many studies. Based on these, we propose the hypothesis that SARS-CoV-2 affects male reproductive function by regulating autophagy. This hypothesis may provide a new idea for future treatment of COVID-19 male patients with reproductive function injury, and it can also prompt medical staff and patients to consciously check their reproductive function.


Assuntos
Autofagia/fisiologia , Betacoronavirus , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/fisiopatologia , Reprodução/fisiologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Genitália Masculina/patologia , Genitália Masculina/fisiopatologia , Genitália Masculina/virologia , Humanos , Infertilidade Masculina/etiologia , Infertilidade Masculina/patologia , Infertilidade Masculina/fisiopatologia , Masculino , Modelos Biológicos , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Espermatozoides/patologia , Espermatozoides/virologia
4.
Life Sci ; 254: 117767, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32407848

RESUMO

OBJECTIVE: Heat stress shock affects the generation of free radicals and can have a harmful effect on spermatogenesis. Photobiomodulation (PBM) is very effective in andrology for treating male infertility. This research aimed at the evaluation of the impacts of PBM on spermatogenesis on the transient scrotal hyperthermia-induced oligospermia mouse model. MATERIALS AND METHODS: This experimental research divided 24 mice into the following four groups: (1) Control, (2) Scrotal hyperthermia, (3) Scrotal hyperthermia receiving laser 0.03 J/cm2 for 30 s for each testis, 35 days after induction of scrotal hyperthermia every other day for 35 days, and (4) Scrotal hyperthermia receiving laser 0.03 J/cm2 for 30 s for each testis, immediately after induction of scrotal hyperthermia every other day for 35 days. Scrotal hyperthermia was induced by water bath with 43 °C for 30 min. Then, the mice were euthanized, and their sperm samples were collected for sperm parameters analysis. Then, we took the testis samples for histopathological experimentations, serum testosterone level, reactive oxygen species (ROS), RNA extraction for the examination of IL1-α, IL6 and TNF-α genes expression as well as production and glutathione disulfide (GSH) activity. KEY FINDINGS: Our outputs indicated that PBM could largely improve the sperms parameters and stereological parameters, like spermatogonia, primary spermatocyte, round spermatid and Leydig cells together with an increasing level of the serum testosterone and GSH activity compared to the scrotal hyperthermia induced mice. In addition, it was found that the diameter of seminiferous tubules, ROS production, as well as the expression of IL1-α, IL6, and TNF-α genes significantly decreased in the treatment groups by PBM compared to the scrotal hyperthermia induced mice, but there was not a significant difference in terms of testis weight and Sertoli cells between the studied groups. SIGNIFICANCE: It could be concluded that PBM may be regarded as an alternative treatment for improving the spermatogenesis process in the scrotal hyperthermia induced mice.


Assuntos
Terapia com Luz de Baixa Intensidade/métodos , Escroto/metabolismo , Espermatogênese/efeitos dos fármacos , Animais , Febre/metabolismo , Resposta ao Choque Térmico/fisiologia , Temperatura Alta , Hipertermia Induzida/métodos , Infertilidade Masculina/patologia , Células Intersticiais do Testículo/metabolismo , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Escroto/patologia , Células de Sertoli/metabolismo , Espermatozoides/patologia , Testículo/efeitos dos fármacos
5.
Zhongguo Zhong Yao Za Zhi ; 45(4): 755-763, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237475

RESUMO

The aim of this paper was to observe the toxic effect of Tripterygium Glycosides Tablets on the reproductive system of Ⅱ type collagen induced arthritis(CIA) male rats, and to explore the toxic mechanism preliminarily. Fifty SD rats were randomly divided into normal control group(Con), model group(CIA), Tripterygium Glycosides Tablets clinical equivalent dose groups of 1, 2, 4 times(9, 18, 36 mg·kg~(-1)), 10 rats in each group, and were given by gavage once a day for 42 days after the first immunization. The organ index of testis and epididymis were calculated on days 21 and 42. Histopathological and morphological changes of testis and epididymis were observed under optical microscope. Sperm count, sperm malformation rate and sperm kinetic parameters in epididymal tissues were observed by computer assisted sperm analysis(CASA). The concentration of testosterone(T), nitric oxide synthase(NOS) and aromatase(CYP19 A1) in serum were detected by ELISA. Immunohistochemistry was used to observe the expression of Bax and Bcl-2 related proteins in the apoptosis pathway of testis and epididymis. The results showed that, compared with Con group, CIA group significantly increased the rate of testicular spermatogenic tubule lesion and sperm malformation, decreased the average path speed, and no significant changes were observed in other groups. Tripterygium Glycosides Tablets at 4 times clinical equivalent dose can significantly reduce the testis index(P<0.01), each dose group can reduce the epididymis index(P<0.05). Each dose group of Tripterygium Glycosides Tablets could cause different degrees of damage to the testis and epididymis, the proportion of testicular histopathology lesions increased, the number of spermatogenic cells in the seminiferous tubules decreased, and so on. It could reduce the number of sperm, increase the rate of sperm deformity, make the parameters of sperm dynamics abnormal, and so on. Tripterygium Glycosides Tablets at 4 times dose could significantly reduce the content of serum sex hormone T and key enzyme of androgen synthesis(P<0.05 or P<0.01), but had no effect on CYP19 A1. The expression of Bax and Bcl-2 in testis and epididymis were increased by 2 and 4 times doses of Tripterygium Glycosides Tablets(P<0.05, P<0.01 or P<0.01). The results showed that 21 d administration of Tripterygium Glycosides Tablets at equal or higher doses could induce obvious toxic effect to the reproductive organs of CIA male rats, and lower the level of serum sex hormone T and the key enzyme of androgen synthesis, NOS. The mechanism of abnormal changes of Bax and Bcl-2 in Testis and epididymis is still to be elucidated.


Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Genitália Masculina/efeitos dos fármacos , Glicosídeos/toxicidade , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Tripterygium/química , Animais , Artrite Experimental , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Espermatozoides/patologia , Comprimidos , Testículo/patologia
6.
Mutat Res ; 850-851: 503145, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32247555

RESUMO

5-Fluorouracil (5-FU) is a widely used antineoplastic drug. In this work, a comprehensive study was performed to detect the extent of chromosomal damage and morphological sperm defects induced by 5-FU in male mice and the possible protective role of the iridoids-rich fraction of Pentas lanceolata leaves (IFPL). Six main groups were examined in micronucleus and chromosomal assays: I- control negative, II- control positive (i.p. treated with single dose of 75 mg/kg 5-FU), III- control plant (orally administrated IFPL, 300 mg/kg, 5 consecutive days), and IV-VI- treated with IFPL (100, 200 and 300 mg/kg, 5 consecutive days) plus 5-FU (i.p. treated at the last day). Samples were taken 24 h post treatment. The study of morphological sperm anomalies, single and repeated treatments were examined and samples were taken after 35 days from the 1st treatment. In bone marrow, 5-FU induced a significant increase in the micro-nucleated polychromatic erythrocytes, chromosome anomalies (CAs) and also cytotoxic effects. A significant percentage of CAs was recorded in spermatocytes after 5-FU treatment reached 22.80 ± 1.32 vs 4.20 ± 0.37 for control (mainly X-Y univalent, 90%). IFPL was recorded to be non-mutagenic in all tests examined. In addition, it alleviated the previous defects in a dose-dependent manner. A significant and dramatic increase in the percentage of morphological sperm defects was recorded after single and repeated treatments with 5-FU reached 13.24 ± 0.24, 30.42 ± 0.32 respectively vs 2.56 ± 0.14 for control. Amorphous head-sperm and sperm with coiled tail were the most pronounced types of abnormalities. Significant protection was detected with the highest tested dose of IFPL. In conclusion: 5-FU demonstrated to be a genotoxic agent. Its genotoxicity in germ cells is serious and may lead to reproductive toxicity, infertility or heritable defects. The results also demonstrated the biosafety of IFPL and its possible protective role in combined treatment with 5-FU.


Assuntos
Iridoides/farmacologia , Extratos Vegetais/farmacologia , Rubiaceae/química , Espermatozoides/efeitos dos fármacos , Animais , Aberrações Cromossômicas/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Iridoides/química , Masculino , Camundongos , Testes de Mutagenicidade , Extratos Vegetais/química , Espermatócitos/efeitos dos fármacos , Espermatócitos/patologia , Espermatozoides/patologia
7.
Int J Nanomedicine ; 15: 1853-1862, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32256064

RESUMO

Background: Curcumin has shown many pharmacological activities in both preclinical and clinical studies. Many technologies have been developed and applied to improve the solubility and bioavailability of curcumin, especially the nanotechnology-based delivery systems. However, there has been evidence that certain nanoparticles have potential reproductive toxicity in practice. Methods: Curcumin-poly (lactic-co-glycolic acid) (PLGA)-PEG nanoparticles (Cur-PLGA-NPs for short) were prepared. The Cur-PLGA-NPs were evaluated with its effect on the proliferation of mouse testicular cell lines in vitro and spermatogenesis in vivo, while PLGA-NPs were used as control. For animal experiments, male BALB/c mice were treated with 20 mg/kg of Cur-PLGA-NPs for continuous 10 days via tail vein injection. Results: We found the curcumin nanoparticles suppressed the proliferation of testicular cell lines in vitro. Furthermore, a short-term intravenous delivery of curcumin-loaded nanoparticles could be harmful to the differentiation of spermatogonia, the elongation of spermatids, as well as the motility of mature sperms. Conclusion: In the present study, we disclosed the acute damage on mouse spermatogenesis and sperm parameters by curcumin-loaded nanoparticles. Our results suggested that the reproductive toxicity of nanoformulated curcumin needs to be prudently evaluated before its application.


Assuntos
Curcumina/efeitos adversos , Nanopartículas/efeitos adversos , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Curcumina/administração & dosagem , Portadores de Fármacos/efeitos adversos , Portadores de Fármacos/química , Masculino , Camundongos Endogâmicos BALB C , Nanopartículas/química , Poliésteres/química , Polietilenoglicóis/química , Células de Sertoli/efeitos dos fármacos , Espermatogônias/efeitos dos fármacos , Espermatogônias/patologia , Espermatozoides/patologia
8.
Ecotoxicol Environ Saf ; 197: 110622, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32311616

RESUMO

Sperm morphology and performance traits are key determinants of male fertilization success, particularly when females copulate with multiple males. Such sperm traits have been reported to be influenced by environmental pollutants in various animals; however, such studies remain rare in free-living birds exposed to heavy metal pollution. In the present study, we selected tree sparrow (Passer montanus) as the study object to explore the effect of long-term environmental heavy metal pollution on sperm morphology (assessed mainly by using the dimensions of different sperm components and the sperm abnormality rates) and sperm performance (indicated by sperm velocity), and to elucidate potential relationships between variations in sperm morphology and performance. Sperm ATP concentration was also assessed considering sperm morphology and performance could be linked via energy availability. According to our results, tree sparrows from heavy metal polluted area (1) accumulated cadmium at a higher level in their testes; (2) produced longer sperm with lower abnormality rates, in addition to sperm with longer flagella and smaller head/flagellum ratios; (3) their sperm swam faster compared to those from the relatively unpolluted area, while no differences were observed in sperm ATP concentrations. We also found that the levels of lead and cadmium in testes affected the sperm nucleus length, and the level of copper in testes was negatively related to the proportions of abnormal sperm. Furthermore, the present study showed that sperm velocity was negatively correlated with sperm head lengths, head/flagellum ratios and ATP concentrations. Our study results reveal that sperm morphology and performance in tree sparrows show positive variations to maximize male fertility ability under long-term environmental heavy metal pollution, where males increase sperm flagellum lengths to decrease head/flagellum ratios, as opposed to varying sperm energy production, to achieve higher sperm velocity.


Assuntos
Poluentes Ambientais/toxicidade , Metais Pesados/toxicidade , Pardais/crescimento & desenvolvimento , Espermatozoides/efeitos dos fármacos , Animais , Cádmio/toxicidade , Feminino , Fertilidade/efeitos dos fármacos , Masculino , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/patologia
9.
Toxicology ; 438: 152463, 2020 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-32294493

RESUMO

Methyl parathion (Me-Pa) is an extremely toxic organophosphorus pesticide still used in developing countries. It has been associated with decreased sperm function and fertility and with oxidative and DNA damage. The blood-testis barrier (BTB) is a structure formed by tight junction (TJ) proteins in Sertoli cells and has a critical role in spermatogenesis. We assessed the effect of repeated doses of Me-Pa (3-12 mg/kg/day for 5 days, i.p.) on sperm quality, lipid oxidation, DNA integrity, and BTB permeability in adult male mice and explored oxidation as a mechanism of toxicity. Me-Pa caused dose-dependent effects on sperm quality, lipoperoxidation, and DNA integrity. Testis histology results showed the disruption of spermatogenesis progression and atrophy of seminiferous tubules. The pesticide opened the BTB, as evidenced by the presence of a biotin tracer in the adluminal compartment of the seminiferous tubules. This effect was not observed after 45 days of exposure when a spermatogenic cycle had completed. The coadministration of the antioxidant α-tocopherol (50 mg/kg/day for 5 days, oral) prevented the effects of Me-Pa on sperm quality, DNA and the BTB, indicating the importance of oxidative stress in the damage generated by Me-Pa. As evidenced by immunochemistry, no changes were found in the localization of the TJ proteins of the BTB, although oxidation (carbonylation) of total proteins in testis homogenates was detected. Our results show that Me-Pa disturbs the BTB and that oxidation is involved in the observed toxic effects on sperm cells.


Assuntos
Barreira Hematotesticular/efeitos dos fármacos , Permeabilidade Capilar/efeitos dos fármacos , Inibidores da Colinesterase/toxicidade , Dano ao DNA , Metil Paration/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Praguicidas/toxicidade , Espermatozoides/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/farmacologia , Barreira Hematotesticular/metabolismo , Barreira Hematotesticular/patologia , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos ICR , Carbonilação Proteica/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/patologia
10.
Urol Clin North Am ; 47(2): 157-164, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32272987

RESUMO

Guiding a couple with nonobstructive azoospermia requires an integrated approach to care by the urologist and the reproductive endocrinologist. After informing the couple of the implications of the diagnosis, care must be taken to outline the options of parenthood. Most experts agree that sperm retrieval in men can be challenging. This article describes various options of sperm retrieval, historic and contemporary, and highlights the advantages and disadvantages of each. The authors find that using a testicular map can invariably help guide sperm retrieval and overall fertility care. The right approach is one that involves a shared decision with the couple.


Assuntos
Azoospermia/diagnóstico , Azoospermia/genética , Biópsia por Agulha Fina/métodos , Recuperação Espermática , Testículo/patologia , Azoospermia/etiologia , Humanos , Masculino , Microdissecção , Análise do Sêmen , Recuperação Espermática/efeitos adversos , Espermatozoides/patologia
11.
Toxicol Appl Pharmacol ; 393: 114942, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32142724

RESUMO

Implications of lead (Pb) exposure in dysregulated spermatogenesis in sexually active individuals during adulthood is well established; however, the effect of Pb exposure on spermatogenesis in the early stages of puberty is not clear yet. Moreover, the mechanism of Pb mediated dysregulation of spermatogenesis in adults is also poorly understood. Exposure to environmental toxicants during puberty may cause serious consequences in adulthood causing developmental retardations, especially in the reproductive system. Here we investigated the effects of lead exposure on spermatogenesis at the onset of puberty and the underlying mechanisms of these effects. Male ICR mice were exposed to low (50 mg/L) and high (200 mg/L) doses of Pb through the drinking water for 90 days. At the end of this period, the blood Pb level of the low-dose and high-dose exposure groups were found 6.14 ± 0.34 µg/dL and 11.92 ± 2.92 µg/dL respectively which were in agreement with the US CDC-recommended (5 µg/dL) and Chinese CDC-recommended (10 µg/dL) reference blood Pb level for the children. Although no visible toxicity was observed in either group, Pb exposure caused considerable histopathological changes in testis and epididymis; increased sperm DNA fragmentation indices as well as disrupted sperm heads and head-neck conjunctions. Moreover, both low and high-dose Pb exposures caused aberrant expressions of several important spermatogenesis-related genes in epididymis and testis. These results suggest that although the blood Pb levels are close to the recommended-reference values, low dose Pb exposure at the onset of puberty can disrupt spermatogenesis-related gene expression and cause abnormal mouse spermatogenesis.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Infertilidade Masculina/induzido quimicamente , Intoxicação por Chumbo/complicações , Espermatogênese/efeitos dos fármacos , Espermatogênese/genética , Animais , Fragmentação do DNA , Água Potável , Epididimo/patologia , Infertilidade Masculina/patologia , Chumbo/sangue , Masculino , Camundongos , Camundongos Endogâmicos ICR , Maturidade Sexual , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Testículo/patologia
12.
Anim Sci J ; 91(1): e13328, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32219925

RESUMO

This study was aimed to investigate whether and how Rutin protects boar sperm against cryoinjury during cryopreservation. Five concentrations of Rutin with 0.2, 0.4, 0.6, 1.0, and 2.0 mM were added to the freezing extender of boar sperm, respectively, and the effects on quality and function of boar sperm after freezing-thawing were assessed. The results showed that the sperm motility, mitochondrial activity, plasma membrane integrity, and acrosomal integrity were significantly improved in 0.4 mM and 0.6 mM Rutin groups (p < .05). Compared with ganoderma lucidum polysaccharide (GLP) or Tanshinone IIA, Rutin exhibited higher rates of mitochondrial activity and acrosome integrity (p < .05). Mechanistically, the addition of Rutin at the concentration of 0.6, 0.8, and 1.0 mM significantly attenuated ROS accumulation and MDA production by improving antioxidant enzymatic activity, including SOD, CAT, and GSH-Px (p < .05). Functionally, a higher penetration rate and the increased total efficiency of fertilization were observed in the 0.4, 0.6, and 1.0 mM Rutin groups than in the control group (p < .05). Moreover, the addition of Rutin (0.6 mM) significantly induced an increase in both the cleavage and blastocyst rates (p < .05). In summary, supplementation with Rutin in cryopreservation medium protects boar sperm against ROS attack by enhancing the antioxidative defense.


Assuntos
Antioxidantes/uso terapêutico , Criopreservação , Congelamento/efeitos adversos , Rutina/farmacologia , Preservação do Sêmen/efeitos adversos , Preservação do Sêmen/métodos , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/patologia , Acrossomo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Membrana Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Mitocôndrias/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Espermatozoides/citologia , Espermatozoides/metabolismo , Superóxido Dismutase/metabolismo , Suínos
13.
Toxicology ; 436: 152428, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32151602

RESUMO

The increase in human infertility prevalence due to male reproductive disorders has been associated with extensive endocrine-disrupting chemical (EDC) exposure. Acrylamide (AA) is a compound formed spontaneously during heat processing of some foods that are mainly consumed by children and adolescents. In this study, we evaluated the prepubertal AA exposure effects on male adult reproductive physiology using a prepubertal experimental model to analyze the pubertal development, spermatogenesis hormones levels and genes expression involved in male reproductive function. This study is the first one to use the validated protocol to correlate the AA exposure with puberty development, as well as the AA-induced endocrine disrupting effects on reproductive axis. AA did not affect the age at puberty, the reproductive organ's weight and serum hormonal levels. AA reduces spermatogenesis, induces morphological and functional defects on sperm and alters transcript expression of sexual hormone receptors (Ar and Esr2), the transcript expression of Tnf, Egr2, Rhcg and Lrrc34. These findings suggest that excessive AA consumption may impair their reproductive capacity at adulthood, despite no changes in hormonal profile being observed.


Assuntos
Acrilamida/toxicidade , Disruptores Endócrinos/toxicidade , Contaminação de Alimentos , Infertilidade Masculina/induzido quimicamente , Desenvolvimento Sexual/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Fatores Etários , Animais , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Relação Dose-Resposta a Droga , Proteína 2 de Resposta de Crescimento Precoce/genética , Proteína 2 de Resposta de Crescimento Precoce/metabolismo , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Infertilidade Masculina/metabolismo , Infertilidade Masculina/patologia , Infertilidade Masculina/fisiopatologia , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Ratos Wistar , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Medição de Risco , Espermatozoides/metabolismo , Espermatozoides/patologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
14.
Toxicology ; 437: 152439, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32197949

RESUMO

Cyclophosphamide (CP) is widely used as chemotherapy in various cancers; however, testicular atrophy has been encountered as an associated adverse effect. Oxidative stress, enhanced endoplasmic reticulum (ER) stress, and subsequent apoptosis are involved in the molecular mechanisms of CP-induced testicular toxicity. In addition to the cardiovascular benefits of LCZ696 (sacubitril/valsartan (VAL)), neprilysin inhibition was shown to mediate Ca2+ sequestration inside the ER. Furthermore, long noncoding RNA taurine-upregulated gene 1 (lncRNA TUG1) was shown to ameliorate apoptosis in various diseases. This tempted us to investigate the possible benefit of LCZ696 against CP-induced testicular dysfunction in rats through neprilysin inhibition axis, and the downstream apoptotic cascade, with highlighting the impact of lncRNA TUG1 in regulating testicular toxicity. Sixty adult male Wistar rats were randomly allocated as control, LCZ696, VAL, CP, CP + LCZ696, and CP + VAL. Testicular atrophy was induced by single-dose injection of CP (200 mg/kg; i.p.). LCZ696 treated group received LCZ696 (30 mg/kg; p.o.) for 6 days, with CP (200 mg/kg; i.p.) single-dose on day 5. LCZ696 increased lncRNA TUG1 expression, improved sperm characteristics, hormonal profile, testicular function, antioxidant defences, and Bcl-2. The histopathological picture and reduced oxidative and ER stress markers, aligned with declined Bax, caspase-3 and the expression of CHOP, PUMA, Noxa, Bim, and p53, with a subtle superior effect over VAL-treated group. In conclusion, the current study highlights the promising impact of LCZ696 in ameliorating chemotherapy-induced testicular atrophy; yet, further investigation regarding longer duration and different doses of LCZ696 is warranted.


Assuntos
Aminobutiratos/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Apoptose/efeitos dos fármacos , Ciclofosfamida/toxicidade , Neprilisina/antagonistas & inibidores , Inibidores de Proteases/farmacologia , RNA Longo não Codificante/metabolismo , Testículo/efeitos dos fármacos , Tetrazóis/farmacologia , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Atrofia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Masculino , Neprilisina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , RNA Longo não Codificante/genética , Ratos Wistar , Transdução de Sinais , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/patologia , Testículo/enzimologia , Testículo/patologia
15.
Biochim Biophys Acta Mol Cell Res ; 1867(7): 118704, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32194132

RESUMO

Exocytosis of spermatozoon's secretory vesicle, named acrosome reaction (AR), is a regulated event that plays a central role in fertilization. It is coupled to a complex calcium signaling. Ceramide is a multitasking lipid involved in exocytosis. Nevertheless, its effect on secretion is controversial and the underlying cellular and molecular mechanisms remain unknown. Human spermatozoa are useful to dissect the role of ceramide in secretion given that the gamete is not capable to undergo any trafficking mechanisms other than exocytosis. We report for the first time, the presence of sphingolipid metabolism enzymes such as neutral-sphingomyelinase and ceramide synthase in sperm. Ceramidases are also present and active. Both the addition of cell-permeable ceramide and the rise of the endogenous one, increase intracellular calcium acting as potent inducers of exocytosis. Ceramide triggers AR in capacitated spermatozoa and enhances the gamete response to progesterone. The lipid induces physiological ultrastructural changes in the acrosome and triggers an exocytosis-signaling cascade involving protein tyrosine phosphatase 1B and VAMP2. Real-time imaging showed an increment of calcium in the cytosol upon ceramide treatment either in the absence or in the presence of extracellular calcium. Pharmacological experiments demonstrate that at early stages the process involves ryanodine receptors, CatSper (calcium channel of sperm), and store-operated calcium channels. We set out the signaling sequence of events that connect ceramide to internal calcium mobilization and external calcium signals during secretion. These results allow the coordination of lipids and proteins in a pathway that accomplishes secretion. Our findings contribute to the understanding of ceramide's role in regulated exocytosis and fertilization.


Assuntos
Reação Acrossômica/genética , Proteína Tirosina Fosfatase não Receptora Tipo 1/genética , Espermatozoides/efeitos dos fármacos , Proteína 2 Associada à Membrana da Vesícula/genética , Acrossomo/efeitos dos fármacos , Acrossomo/metabolismo , Reação Acrossômica/efeitos dos fármacos , Adulto , Cálcio/química , Canais de Cálcio/genética , Sinalização do Cálcio/efeitos dos fármacos , Ceramidas/farmacologia , Citoplasma/efeitos dos fármacos , Citoplasma/genética , Exocitose/genética , Fertilização/genética , Humanos , Masculino , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Vesículas Secretórias/efeitos dos fármacos , Vesículas Secretórias/genética , Espermatozoides/patologia
16.
Biomed Res Int ; 2020: 6279795, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32104701

RESUMO

This review analyses the genetic mechanisms of acephalic spermatozoa (AS) defects, which are associated with primary infertility in men. Several target genes of headless sperms have been identified but intracytoplasmic sperm injection (ICSI) outcomes are complex. Based on electron microscopic observations, broken points of the sperm neck are AS defects that are based on various genes that can be classified into three subtypes: HOOK1, SUN5, and PMFBP1 genes of subtype II; TSGA10 and BRDT genes of subgroup III, while the genetic mechanism(s) and aetiology of AS defects of subtype I have not been described and remain to be explored. Interestingly, all AS sperm of subtype II achieved better ICSI outcomes than other subtypes, resulting in clinical pregnancies and live births. For subtype III, the failure of clinical pregnancy can be explained by the defects of paternal centrioles that arrest embryonic development; for subtype I, this was due to a lack of a distal centriole. Consequently, the embryo quality and potential ICSI results of AS defects can be predicted by the subtypes of AS defects. However, this conclusion with regard to ICSI outcomes based on subtypes still needs further research, while the existence of quality of oocyte and implantation failure in women cannot be ignored.


Assuntos
Infertilidade Masculina/genética , Oócitos/metabolismo , Espermatozoides/patologia , Adulto , Implantação do Embrião/genética , Implantação do Embrião/fisiologia , Feminino , Humanos , Infertilidade Masculina/patologia , Masculino , Proteínas de Membrana/genética , Proteínas Associadas aos Microtúbulos/genética , Oócitos/crescimento & desenvolvimento , Oócitos/patologia , Gravidez , Taxa de Gravidez , Espermatozoides/crescimento & desenvolvimento
17.
PLoS Genet ; 16(1): e1008585, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31961863

RESUMO

Flagella and cilia are evolutionarily conserved cellular organelles. Abnormal formation or motility of these organelles in humans causes several syndromic diseases termed ciliopathies. The central component of flagella and cilia is the axoneme that is composed of the '9+2' microtubule arrangement, dynein arms, radial spokes, and the Nexin-Dynein Regulatory Complex (N-DRC). The N-DRC is localized between doublet microtubules and has been extensively studied in the unicellular flagellate Chlamydomonas. Recently, it has been reported that TCTE1 (DRC5), a component of the N-DRC, is essential for proper sperm motility and male fertility in mice. Further, TCTE1 has been shown to interact with FBXL13 (DRC6) and DRC7; however, functional roles of FBXL13 and DRC7 in mammals have not been elucidated. Here we show that Fbxl13 and Drc7 expression are testes-enriched in mice. Although Fbxl13 knockout (KO) mice did not show any obvious phenotypes, Drc7 KO male mice were infertile due to their short immotile spermatozoa. In Drc7 KO spermatids, the axoneme is disorganized and the '9+2' microtubule arrangement was difficult to detect. Further, other N-DRC components fail to incorporate into the flagellum without DRC7. These results indicate that Drc7, but not Fbxl13, is essential for the correct assembly of the N-DRC and flagella.


Assuntos
Dineínas/metabolismo , Flagelos/genética , Infertilidade Masculina/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Espermatozoides/metabolismo , Animais , Axonema/genética , Axonema/metabolismo , Axonema/patologia , Feminino , Flagelos/metabolismo , Flagelos/patologia , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Espermatogênese , Espermatozoides/citologia , Espermatozoides/patologia
18.
PLoS One ; 15(1): e0227885, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31945120

RESUMO

The phenomenon of aging arises from multiple, complex interactions causing dysfunction in cells and organs. In particular, fertility drastically decreases with age. Previously, we have demonstrated that the functional characteristics of the bovine oviduct and uterus change with the age-dependent upregulation of inflammation and noted that S100A9 triggers inflammatory responses in oviduct epithelial cells. In the present study, we investigated the hypothesis that S100A9 affects reproductive events to aspect such as sperm function, fertilization, and the development of the embryo in cows. To investigate the effect of S100A9 on bovine sperm, we incubated sperms in vitro with S100A9 for 5 h and observed significantly decreased sperm motility and viability. During in vitro fertilization, S100A9 treatment for 5 h did not affect the rate of fertilization, time of first division of embryos, or embryo development to blastocyst stage. Treatment of 2-cell stage embryos with S100A9 for 5 h significantly reduced the proportion of cells undergoing normal division (4-8 cell embryos) and embryo development to the blastocyst stage. In experiment involving 24 h treatment of 2-cell embryos, the development of all embryos stopped at the 2-cell stage in the S100A9-treated group. In blastocyst-stage embryos, S100A9 treatment significantly stimulated the expression of endoplasmic reticulum (ER) and the mRNA expression of ER stress markers, and activated caspase-3 with subsequent nuclear fragmentation. Pre-treatment with an ER stress inhibitor significantly suppressed caspase-3 activation by the S100A9 treatment, suggesting that S100A9 induces blastocyst dysfunction by apoptosis (via caspase-3 activation) depending on ER stress. These results indicate that direct exposure to S100A9 exerted adverse effects on sperm function and embryo development. These findings suggest that excessive dose of S100A9 may have an adverse effect to the reproductive machinery by inducing inflammation and tissue dysfunction.


Assuntos
Calgranulina B/farmacologia , Desenvolvimento Embrionário/genética , Fertilização In Vitro , Reprodução/efeitos dos fármacos , Animais , Blastocisto/efeitos dos fármacos , Calgranulina B/genética , Caspase 3/genética , Bovinos , Técnicas de Cultura Embrionária , Desenvolvimento Embrionário/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Tubas Uterinas/efeitos dos fármacos , Tubas Uterinas/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Masculino , Gravidez , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia
19.
Development ; 147(2)2020 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-31969357

RESUMO

The development and maintenance of the correct morphology of sperm is important for their functions. Cellular morphogenesis of sperm occurs during the post-meiotic developmental stage; however, little is known about what coordinates this process. In the present study, we investigated the role of A-kinase anchoring protein 3 (AKAP3) during mouse spermiogenesis, using both mouse genetics and proteomics. It was found that AKAP3 is essential for the formation of the specific subcellular structure of the sperm flagellum, motility of sperm and male fertility. Additionally, lack of AKAP3 caused global changes of the sperm proteome and mislocalization of sperm proteins, including accumulation of RNA metabolism and translation factors and displacement of PKA subunits in mature sperm, which may underlie misregulated PKA activity and immotility in sperm. Interestingly, sperm lacking a complete fibrous sheath from both Akap3 and Akap4 null mice accumulated F-actin filaments and morphological defects during post-testicular maturation in the epididymis. These results suggest that the subcellular structures of sperm could be formed via independent pathways, and elucidate the roles of AKAP3 during the coordinated synthesis and organization of the sperm proteome and sperm morphology.


Assuntos
Proteínas de Ancoragem à Quinase A/metabolismo , Infertilidade Masculina/metabolismo , Espermatozoides/metabolismo , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Animais , Sequência de Bases , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Epididimo/metabolismo , Deleção de Genes , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutação/genética , Proteoma/metabolismo , Transdução de Sinais , Espermatozoides/anormalidades , Espermatozoides/patologia , Espermatozoides/ultraestrutura , Frações Subcelulares/metabolismo
20.
Chemosphere ; 242: 125286, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31896186

RESUMO

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


Assuntos
Compostos Benzidrílicos/toxicidade , Dano ao DNA , Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Fenóis/toxicidade , Espermatozoides/efeitos dos fármacos , Fatores Etários , Animais , Humanos , Masculino , Camundongos , Oxirredução , Contagem de Espermatozoides , Espermatozoides/patologia , Testes de Toxicidade Aguda , Testes de Toxicidade Subaguda
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