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2.
Urol Clin North Am ; 47(2): 175-183, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32272989

RESUMO

From a fertility perspective, men with azoospermia represent a challenging patient population. When no mature spermatozoa are obtained during a testicular sperm extraction, patients are often left with limited options, such as adoption or the use of donor sperm. However, it has been reported that round spermatids can be successfully injected into human oocytes and used as an alternative to mature spermatozoa. This technique is known as round spermatid injection (ROSI). Despite the limitations of ROSI and diminished clinical success rates, the use of round spermatids for fertilization may have potential as a treatment modality for men with azoospermia.


Assuntos
Azoospermia/patologia , Infertilidade Masculina/terapia , Injeções de Esperma Intracitoplásmicas , Recuperação Espermática , Espermátides/patologia , Azoospermia/etiologia , Azoospermia/fisiopatologia , Feminino , Fertilização In Vitro , Humanos , Infertilidade Masculina/etiologia , Infertilidade Masculina/patologia , Infertilidade Masculina/fisiopatologia , Masculino , Microdissecção , Gravidez , Resultado da Gravidez , Análise do Sêmen , Espermatogênese/fisiologia
3.
Urol Clin North Am ; 47(2): 219-225, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32272994

RESUMO

Transgenerational epigenetic inheritance provides a mechanism by which environmental exposures and lifestyle decisions can affect the offspring directly through the gamete. It is this pattern of inheritance that has shed light on the fact that preconception lifestyle decisions that a father makes are significant because they can significantly impact the offspring. Understanding the epigenetic alterations in gametes and the potential implications of these changes is key to the health of future generations.


Assuntos
Epigênese Genética/genética , Infertilidade Masculina/genética , Exposição Paterna , Herança Paterna/genética , Espermatogênese/genética , Efeito de Coortes , Metilação de DNA/genética , Humanos , Infertilidade Masculina/etiologia , Masculino , Exposição Paterna/efeitos adversos
4.
Urol Clin North Am ; 47(2): 245-255, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32272996

RESUMO

Personalized medicine gathers the most relevant data involved in human health. Currently, the diagnosis of male infertility is limited to spermiogram, which does not provide information on the male fertile potential. New diagnostic methods are required. The application of omics techniques in the study of male reproductive health renders a huge amount of data providing numerous novel infertility biomarkers, from genes to metabolites, to diagnose the cause of male infertility. Recent studies hold the promise that these biomarkers will allow a noninvasive infertility diagnosis and the improvement of the sperm selection techniques.


Assuntos
Infertilidade Masculina/etiologia , Infertilidade Masculina/terapia , Medicina de Precisão , Biomarcadores/análise , Genômica , Humanos , Infertilidade Masculina/diagnóstico , Masculino , Metabolômica , Medicina de Precisão/tendências , Espermatogênese/fisiologia
5.
Urol Clin North Am ; 47(2): 227-244, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32272995

RESUMO

Infertility caused by chemotherapy or radiation treatments negatively impacts patient-survivor quality of life. The only fertility preservation option available to prepubertal boys who are not making sperm is cryopreservation of testicular tissues that contain spermatogonial stem cells (SSCs) with potential to produce sperm and/or restore fertility. SSC transplantation to regenerate spermatogenesis in infertile adult survivors of childhood cancers is a mature technology. However, the number of SSCs obtained in a biopsy of a prepubertal testis may be small. Therefore, methods to expand SSC numbers in culture before transplantation are needed. Here we review progress with human SSC culture.


Assuntos
Células-Tronco Germinativas Adultas/transplante , Preservação da Fertilidade/métodos , Infertilidade Masculina/prevenção & controle , Neoplasias/terapia , Espermatogênese/fisiologia , Células-Tronco Germinativas Adultas/fisiologia , Humanos , Infertilidade Masculina/etiologia , Masculino , Espermatogênese/efeitos dos fármacos , Espermatogênese/efeitos da radiação , Transplante de Células-Tronco/métodos
6.
Toxicol Lett ; 326: 83-98, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32112876

RESUMO

Arsenic (As) has been implicated in causing reproductive toxicity, but the precise cellular pathway through which the As toxicity in mature F1- male mice hypothalamic-pituitary- gonadal- sperm (HPG-S) axis is induced has not well been documented. Hence, parental mice were treated to As2O3 (0, 0.2, 2, and 20 ppm in deionized water) from five weeks before mating until weaning, and the male pups from weaning to maturity. Afterward, the markers of oxidative stress, mitochondrial impairment, and autophagy as fundamental mechanisms of cytotoxicity and organ injury were evaluated. Higher As2O3 doses (2 and 20 ppm) were a potent inducer of oxidative stress, mitochondrial dysfunction, and autophagy in HPG-S axis. Concomitant with a dose-dependent increase in the number of MDC-labeled autophagic vacuoles in the HPG axis, an adverse dose-dependent effect was observed on the mean body weight, litter size, organ coefficient, and spermatogenesis. Transmission electron microscopy also revealed more autophagosomes at high As2O3 dosage. Concomitant with a dose-dependent increment in gene expression of PI3K, Atg5, Atg12, as well as protein expression of Beclin1, LC3- I, II, P62 in HPG axis tissues and Atg12 in the pituitary; a dose-dependent decrease in mTOR gene expression was recorded in the HPG tissues of mature F1-males. These observations provide direct evidence that oxidative stress-induced mitochondrial impairments and autophagic cell death, through AMPK/TSC/mTOR and LC3 related pathways, are fundamental mechanisms for As2O3- induced toxicity on the reproductive system in mature male mice offspring.


Assuntos
Arsênico/toxicidade , Autofagia/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Animais , Masculino , Camundongos
7.
Toxicol Lett ; 326: 114-122, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32199951

RESUMO

Previous studies have reported the reproductive toxicity of cadmium (Cd); however, the effect of Cd on spermatogenesis and the underlying mechanism remain to be elucidated. In this study, mouse Leydig TM3 cells were treated with CdCl2 (0, 5, 10 and 50 µM) for 24 h to evaluate cytotoxicity, and C57BL/6 mice were treated intragastrically with 0.4 mL CdCl2 (0, 0.01, 0.05 and 0.1 g/L) for 2 months to investigate changes in spermatogenesis. The results showed that Cd aggravated apoptosis and proliferation in a dose-dependent manner, concomitant with deteriorated spermatogenesis and testosterone synthesis. For mechanism exploration, RNA-seq was used to profile alterations in gene expression in response to Cd, and the results indicated focus on P53/JNK signalling pathways and membrane proteins. We found that P53/JNK signalling pathways were activated upon Cd treatment, with the Cd-triggered downregulation of the vdac2 gene. P53/JNK pathway blockade ameliorated the Cd-induced inhibition of steroidogenic acute regulatory protein (STAR) expression and testosterone synthesis. Additionally, vdac2 knockdown in TM3 cells contributed to the phosphorylation of JNK/P53 and reduced the testosterone content. Vdac2 overexpression rescued the aforementioned Cd-induced events. Collectively, our study identified an innovative biomarker of Cd exposure in mice. The results demonstrated that vdac2 downregulation inhibits spermatogenesis via the JNK/P53 cascade. This finding may contribute to our understanding of the regulatory mechanism of Cd reproductive toxicity and provide a candidate list for sperm abnormality factors and pathways.


Assuntos
Apoptose/efeitos dos fármacos , Cádmio/toxicidade , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Canal de Ânion 2 Dependente de Voltagem/efeitos dos fármacos , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL
8.
Nat Cell Biol ; 22(4): 425-438, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32203416

RESUMO

Piwi proteins are normally restricted in germ cells to suppress transposons through associations with Piwi-interacting RNAs (piRNAs), but they are also frequently activated in many types of human cancers. A great puzzle is the lack of significant induction of corresponding piRNAs in cancer cells, as we document here in human pancreatic ductal adenocarcinomas (PDACs), which implies that such germline-specific proteins are somehow hijacked to promote tumorigenesis through a different mode of action. Here, we show that in the absence of piRNAs, human PIWIL1 in PDAC functions as an oncoprotein by activating the anaphase promoting complex/cyclosome (APC/C) E3 complex, which then targets a critical cell adhesion-related protein, Pinin, to enhance PDAC metastasis. This is in contrast to piRNA-dependent PIWIL1 ubiquitination and removal by APC/C during late spermiogenesis. These findings unveil a piRNA-dependent mechanism to switch PIWIL1 from a substrate in spermatids to a co-activator of APC/C in human cancer cells.


Assuntos
Adenocarcinoma/genética , Proteínas Argonauta/genética , Carcinoma Ductal Pancreático/genética , Moléculas de Adesão Celular/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Nucleares/genética , Neoplasias Pancreáticas/genética , RNA Interferente Pequeno/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Anáfase , Ciclossomo-Complexo Promotor de Anáfase/genética , Ciclossomo-Complexo Promotor de Anáfase/metabolismo , Animais , Proteínas Argonauta/metabolismo , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Moléculas de Adesão Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Metástase Linfática , Masculino , Camundongos , Camundongos Knockout , Camundongos Nus , Proteínas Nucleares/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Espermatogênese/genética , Ubiquitinação , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Sheng Li Xue Bao ; 72(1): 75-83, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32099985

RESUMO

Spermatogenesis is composed of a series of complex biological events, which are regulated by complex factors. There is a phenomenon of delayed translation in spermatogenesis, so the changes of transcription and protein expression are not completely consistent. Thus post-translational modifications (PTMs) play a key role in spermatogenic biological events. In recent years, the development of proteomics has deepened the discovery of PTM. This paper reviews the advances in multiple PTMs proteomic during testicular spermatogenesis. Their effects on sperm function and fertility, as well as their significance for future diagnosis and treatment are discussed.


Assuntos
Processamento de Proteína Pós-Traducional , Proteômica , Espermatogênese , Espermatozoides/fisiologia , Animais , Fertilidade , Humanos , Masculino
10.
Gene ; 737: 144481, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32070749

RESUMO

Studies have recently demonstrated that mesenchymal stem cells (MSCs) have therapeutic capabilities on many diseases and this effect is mainly mediated by miRNAs. However, the actual mechanism of MSCs paracrine effect on testis to improve male fertility is still elusive. Herein, we evaluated the altered expression of some spermatogenesis-related miRNAs and their target genes following transplantation of bone marrow (BM)-derived MSCs into testes of busulfan-induced azoospermic rats using real time PCR. Transplantation of MSCs improved fertility of azoospermic rats as revealed by enhanced serum levels of testosterone and estradiol, and upregulated expression of germ cell­specific genes. Azo rats injected with MSCs also exhibited a significant downregulated expression of miRNA-19b, miRNA-100, miRNA-141, miRNA­146a, miRNA-429, and let­7a and a significant upregulated expression of miRNA-21, miRNA-34b, miRNA-34c, miRNA-122, miRNA-449a, miRNA-449b, and miRNA-449c in the testis as compared to Azo rats injected with phosphate buffer saline. Transplantation of MSCs was also accompanied with restoration of the disrupted expression of Ccnd1, E2F1, Myc, and PLCXD3 (target genes for miRNA-34 and miRNA­449 clusters) and ERα and AKT1 (target genes for miRNA-100 and let­7a) to level comparable to that of the fertile group. Upon these data, we infer that BM-MSCs can improve fertility of azoospermic rats and this effect was followed by altered expression of some spermatogenesis-related miRNAs and their target genes. These findings provide MSCs as a promising and effective cell-based therapeutic method for azoospermic patients, but further investigations are required before clinical application.


Assuntos
Azoospermia/induzido quimicamente , Bussulfano/toxicidade , Células-Tronco Mesenquimais/efeitos dos fármacos , MicroRNAs/genética , Animais , Azoospermia/genética , Azoospermia/fisiopatologia , Regulação para Baixo , Feminino , Fertilidade , Masculino , Células-Tronco Mesenquimais/metabolismo , Ratos , Espermatogênese/genética
11.
BMC Med Genet ; 21(1): 33, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-32059713

RESUMO

BACKGROUND: Tudor domain-containing proteins (TDRDs) play a critical role in piRNA biogenesis and germ cell development. piRNAs, small regulatory RNAs, act by silencing of transposons during germline development and it has recently been shown in animal model studies that defects in TDRD genes can lead to sterility in males. METHODS: Here we evaluate gene and protein expression levels of four key TDRDs (TDRD1, TDRD5, TDRD9 and TDRD12) in testicular biopsy samples obtained from men with obstructive azoospermia (OA, n = 29), as controls, and various types of non-obstructive azoospermia containing hypospermatogenesis (HP, 28), maturation arrest (MA, n = 30), and Sertoli cell-only syndrome (SCOS, n = 32) as cases. One-way ANOVA test followed by Dunnett's multiple comparison post-test was used to determine inter-group differences in TDRD gene expression among cases and controls. RESULTS: The results showed very low expression of TDRD genes in SCOS specimens. Also, the expression of TDRD1 and TDRD9 genes were lower in MA samples compared to OA samples. The expression of TDRD5 significantly reduced in SCOS, MA and HP specimens than the OA specimens. Indeed, TDRD12 exhibited a very low expression in HP specimens in comparison to OA specimens. All these results were confirmed by Western blot technique. CONCLUSION: TDRDs could be very important in male infertility, which should be express in certain stages of spermatogenesis.


Assuntos
Azoospermia/genética , Proteínas de Ciclo Celular/genética , DNA Helicases/genética , Infertilidade Masculina/genética , Adulto , Animais , Azoospermia/patologia , Regulação da Expressão Gênica/genética , Humanos , Infertilidade Masculina/patologia , Masculino , RNA Interferente Pequeno/genética , Espermatogênese/genética , Testículo/crescimento & desenvolvimento , Testículo/metabolismo , Testículo/patologia
13.
Gene ; 731: 144335, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-31927007

RESUMO

Deleted in azoospermia-like (DAZL) is essential for mammalian spermatogenesis as it regulates proliferation, development, maturation and functional maintenance of male germ cells. Its expression and regulation vary with different species or in the same animal at different developmental stages, and despite its importance, very little is known about its roles in sheep, especially Tibetan sheep. To investigate the expression patterns and regulatory roles of DZAL in Tibetan sheep testis, testicular tissue was isolated from sheep at three crucial development stages: 3 months old, 1 year old and 3 years old. Using quantitative real-time PCR and Western blot, we found that DAZL mRNA first decreased and then increased with advancing age, while DAZL protein exhibited an opposite expression pattern, with first increased and subsequently decreased levels. Immunohistochemistry and immunofluorescence revealed that DAZL protein was located predominantly in the cytoplasm of Leydig cells and in both the cytoplasm and nucleus of spermatids. ELISA indicated that testosterone content within developing testes was first enhanced and then declined. Our results, taken together, demonstrate, for the first time, that DAZL gene is involved in Tibetan sheep spermatogenesis by regulating the development of spermatids in post-pubertal rams, along with a novel role in functional maintenance of Leydig cells in postnatal rams.


Assuntos
Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Ovinos , Testículo/crescimento & desenvolvimento , Testículo/metabolismo , Animais , Feminino , Perfilação da Expressão Gênica/veterinária , Regulação da Expressão Gênica no Desenvolvimento , Células Intersticiais do Testículo/fisiologia , Masculino , Proteínas de Ligação a RNA/fisiologia , Diferenciação Sexual/genética , Maturidade Sexual/genética , Ovinos/genética , Ovinos/crescimento & desenvolvimento , Ovinos/metabolismo , Espermátides/fisiologia , Espermatogênese/genética , Testosterona/metabolismo , Tibet , Distribuição Tecidual
14.
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
15.
Nat Commun ; 11(1): 40, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31896751

RESUMO

Spermatogonia, which produce sperm throughout the male lifetime, are regulated inside a niche composed of Sertoli cells, and other testis cell types. Defects in Sertoli cells often lead to infertility, but replacement of defective cells has been limited by the inability to deplete the existing population. Here, we use an FDA-approved non-toxic drug, benzalkonium chloride (BC), to deplete testis cell types in vivo. Four days after BC administration, Sertoli cells are preferentially depleted, and can be replaced to promote spermatogenesis from surviving (host) spermatogonia. Seven days after BC treatment, multiple cell types can be engrafted from fresh or cryopreserved testicular cells, leading to complete spermatogenesis from donor cells. These methods will be valuable for investigation of niche-supporting cell interactions, have the potential to lead to a therapy for idiopathic male infertility in the clinic, and could open the door to production of sperm from other species in the mouse.


Assuntos
Compostos de Benzalcônio/farmacologia , Células de Sertoli/transplante , Espermatogônias/citologia , Testículo/citologia , Animais , Animais Recém-Nascidos , Criopreservação , Cães , Masculino , Camundongos Endogâmicos , Camundongos Transgênicos , Técnicas de Cultura de Órgãos , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/patologia , Espermatogênese , Nicho de Células-Tronco , Testículo/efeitos dos fármacos
16.
Chemosphere ; 246: 125772, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31901658

RESUMO

Excessive fluoride (F) ingestion via drinking water interfered with spermatogenesis and lowered sperm quality of human and animals. However, it is still unclear why the effects of fluoride on sperm quality focus on mostly sperm motility rather than sperm count. The objective of this study is to investigate the potential relationship between alteration in the structure and function of sperm flagellum and fluoride exposure in the environment. 40 male mice were allocated to four groups which were treated with 0, 25, 50, 100 mg/L NaF deionized water, respectively, for 8 weeks continuously. The testicular morphology, ultra-structure of fibrous sheath and axoneme of sperm flagellum, and eleven key function genes Akap3, Akap4, Dnah1, Eno4, Cfap43, Cfap44, Hydin, Spef2, Spag6, Spag16, and Cfap69 were examined by histology, transmission electron microscopy, and real-time PCR methods respectively. The results displayed that fluoride damaged the typical "9 + 2″ microtubule structure including fibrous sheathes and axoneme of sperm flagellum in testes of mice. Furthermore, the mRNA and protein expression levels of AKAP3 and AKAP4 related to fibrous sheathes formation, and CFAP43, CFAP44 and HYDIN in axoneme were down-regulated by fluoride exposure. Taken together, we revealed that fluoride altered the structures of the fibrous sheathes and axonemal in sperm flagellum via down-regulating the mRNA and protein expression levels of AKAP3, AKAP4, CFAP43, CFAP44, and HYDIN, which may be one of the reasons that fluoride lowered sperm quality and male reproductive function.


Assuntos
Fluoretos/toxicidade , Cauda do Espermatozoide/ultraestrutura , Testículo/metabolismo , Proteínas de Ancoragem à Quinase A , Animais , Dineínas , Poluentes Ambientais , Fluoretos/metabolismo , Humanos , Infertilidade Masculina , Masculino , Camundongos , Proteínas dos Microtúbulos , Fenótipo , RNA Mensageiro/metabolismo , Motilidade Espermática , Cauda do Espermatozoide/efeitos dos fármacos , Espermatogênese , Espermatozoides/metabolismo
17.
Chemosphere ; 246: 125776, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31918093

RESUMO

The impairments of gestational cadmium (Cd) exposure on testicular development and male fertility in offspring have been reported. Here, we investigated the effect of paternal low-concentration cadmium exposure on testicular development and spermatogenesis in offspring. Five-week-old male mice were exposed to cadmium chloride (100 mg/L) in drinking water for 20 weeks. Results presented that Cd did not affect the testicular histology and sperm count in mice. After mating with untreated females, pregnant mice and pups were then evaluated. No significant difference in the rate for successful pregnancy and the body weight of pups was observed in Cd-exposed mice compared to the controls. Male offspring were given with a chow and high-fat diet from postnatal day (PND) 35 to PND70. Our data indicated that high-fat diet obviously decreased No. of sperm in epididymides of adult offspring due to paternal Cd exposure. Testicular histology revealed that the percentage of seminiferous tubules in stages IX-XII and the atypical residual bodies positive tubules in CdH (paternal cadmium exposure and pubertal high-fat diet) group were higher than these in CdC (paternal cadmium exposure and pubertal chow diet) group. Further analysis demonstrated that high-fat diet markedly accelerated testicular apoptosis, as determined by TUNEL assay and immunostaining for cleaved caspase-3, in male offspring due to paternal Cd exposure. Collectively, high-fat diet exacerbates the damage of testicular development and spermatogenesis in offspring due to paternal cadmium exposure.


Assuntos
Cádmio/toxicidade , Exposição Dietética , Poluentes Ambientais/toxicidade , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Cloreto de Cádmio/toxicidade , Dieta , Feminino , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Túbulos Seminíferos , Espermatozoides/efeitos dos fármacos
18.
Biomed Chromatogr ; 34(4): e4799, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31994209

RESUMO

Spermiogenesis in mammals is an exclusive process during which haploid round spermatids mature into spermatozoa in the testis. Any abnormality in the process of spermiogenesis may result in male infertility. The aim of the present study was to characterize the differentially expressed proteins between round and elongated spermatids in mice using label-free quantitative mass spectrometry. Of the 2411 proteins identified in this study, 333 were differentially expressed with a ≥10-fold change, including 208 upregulated proteins and 125 downregulated proteins in round spermatids relative to elongated spermatids. Gene Ontology analysis showed that these differentially expressed proteins were categorized into 10 types of subcellular localizations, 9 molecular functions, and were involved in 9 biological processes. All the identified proteins participated in 268 different pathways. In addition, ubiquitin-mediated proteolysis and the proteasome pathway, autophagy, lysosome, and apoptosis pathways were involved in the mechanism of spermiogenesis. Our data may provide valuable information for a better understanding of spermiogenesis and help improve the diagnosis and treatment of male factor infertility.


Assuntos
Proteoma/análise , Espermátides/metabolismo , Espermatogênese/fisiologia , Animais , Bases de Dados de Proteínas , Masculino , Redes e Vias Metabólicas , Camundongos , Camundongos Endogâmicos BALB C , Proteínas/análise , Proteínas/classificação , Proteínas/metabolismo , Proteoma/classificação , Proteoma/metabolismo , Espermátides/química
19.
Ecotoxicol Environ Saf ; 190: 110142, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31911389

RESUMO

Cadmium (Cd) has been reported to induce reproductive toxicity. Recent study indicated that aberrant epigenetic regulation of Multidrug resistance 1b (Mdr1b) causes xenobiotic efflux failure at the blood-testis barrier (BTB). However, whether Mdr1b dysregulation is involved in Cd-mediated dyszoospermia and the underlying mechanism remain unknown. In this study, mice were intragastrically administered 0 or 2.5 mg/kg CdCl2 every other day for 2 months to investigate changes in spermatogenesis and epigenetic regulation of Mdr1b. Mouse Leydig cells TM3 were cultured to detect Mdr1b expression localization. We found that the Cd group revealed BTB disruption concomitant with obvious sperm abnormity and dynamic impairment. Hypermethylation and decreased nuclear factor Ya (Nfya) recruitment to the Mdr1b promoter were correlated with low sperm motility in response to Cd. In conclusion, these findings provide in vivo evidence that epigenetic dysregulation of Mdr1b in the BTB is a potential cause of dyszoospermia upon Cd exposure.


Assuntos
Cádmio/toxicidade , Poluentes Ambientais/toxicidade , Espermatogênese/efeitos dos fármacos , Animais , Barreira Hematotesticular/metabolismo , Fator de Ligação a CCAAT , Núcleo Celular/metabolismo , Resistência a Múltiplos Medicamentos , Epigênese Genética , Infertilidade Masculina , Masculino , Camundongos , Regiões Promotoras Genéticas , Motilidade Espermática , Espermatozoides/metabolismo , Testículo/metabolismo
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