No description available.

Delicate epigenetic modifications are essential for production of spermatids during spermatogenesis. DNA methyltransferase 3 (DNMT3), the enzymes involved in adding a methyl group to unmodified DNA, contains three members: DNMT3A, DNMT3B and DNMT3L. The latter lacks methyltransferase activity, but was closely associated with spermatogenesis in many reports. According to the presentation of mature spermatids in testis, azoospermia could be separated into obstructive and non-obstructive categories. Non-obstructive azoospermia is spermatogenesis defective, germ cells absent in seminiferous tube is the most serious type. Therefore, we would like to find out if there are differential expression of DNMT3 family transcripts in testes of azoospermia patients from infertility clinic. Using RT-PCR and qPCR, we found only 5 (29.4%) expressed DNMT3L in 17 non-obstructive patients, whereas all 20 obstructive patients expressed. Both groups were similar in expression levels of DNMT3A and DNMT3B. Nuclei of spermatogonia and spermatocyte were the main immunohisto-chemical localization of DNMT3L protein. Lost of germ cells should be the cause of undetectable DNMT3L expression in azoospermia patients. By this founding, it could serve as an indicator for ability of male germ cell culture in further applications of assisted reproduction.

Orientadores: Carlos Arturo Levi D'Ancona, Paulo Augusto Neves / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T11:43:00Z (GMT). No. of bitstreams: 1 Saade_RicardoDestro_D.pdf: 1299944 bytes, checksum: dfdd6825fd6739a18659a773638e845d (MD5) Previous issue date: 2006 / Resumo: Introdução: O tratamento da infertilidade masculina tem evoluído muito nas últimas décadas. O advento de técnicas de reprodução assistida (RA) e, particularmente, a injeção intracitoplasmática de espermatozóides (ICSI) tornaram possível o tratamento de indivíduos até então considerados inférteis, como os casos de azoospermia obstrutiva e os de azoospermia não obstrutiva. Nestes casos, na impossibilidade de correção cirúrgica, outros procedimentos de obtenção de espermatozóides podem ser realizados como a aspiração microcirúrgica dos epidídimos (MESA), punção aspirativa percutânea dos epidídimos (PESA), aspiração testicular de espermatozóides (TESA) ou a extração testicular (TESE). Objetivos: A proposta de trabalho foi verificar a obtenção de espermatozóides viáveis em até cinco punções percutâneas do epidídimo. Analisar as alterações histológicas inflamatórias e cicatriciais, assim como a densidade de fibras de músculo liso e colágenas nos epidídimos de ratos, após punções. Material e método: O grupo piloto consistiu em quatro animais, sendo dois para estudo da anatomia e da histologia do epidídimo normal e outros dois para avaliação dos efeitos da vasectomia. A vasectomia bilateral foi realizada por meio de laparotomia infra-umbilical. Foi padronizado o lado direito para estudo e o esquerdo como controle. O grupo estudado consistiu em 50 ratos que realizaram vasectomia e foram separados em cinco grupos de I a V, contendo 10 animais cada. Os animais do grupo I foram submetidos a uma punção percutânea trans-escrotal; II a duas punções; III a três punções; IV a quatro punções; V a cinco punções. As punções dos epidídimos foram feitas após 30 dias da vasectomia, com escalpe 25G na cabeça do epidídimo. O material extraído foi suspenso em meio de cultura HTF e analisado em câmara de Makler. O intervalo entre cada punção foi de 15 dias e os animais foram sacrificados após 15 dias da última punção. Os epidídimos foram fixados em líquido de Bouin. Foram realizados estudos histológicos e estereológicos dos epidídimos puncionados. Resultados: O número médio de espermatozóides recuperados nas punções foi de: 48,78 x 106 /ml, 37,55 x 106 /ml, 26,33 x 106 /ml, 33,90 x 106 /ml e 41,34 x 106 /ml, nos grupos I a V, respectivamente. Após a análise histológica, observou-se que as variáveis infiltrado linfoplasmocitário, reação granulomatosa, fibrose e desarranjo estrutural apresentaram diferença significativa a partir da segunda punção. O efeito cumulativo das punções somente foi observado nas variáveis infiltrado linfoplasmocitário e fibrose, mostrando que existe diferença significativa entre os grupos I e II em relação aos grupos III, IV e V. No estudo estereológico, a densidade volumétrica do tecido conjuntivo foi de 21,56%, 27,60%, 35,67%, 37,56% e 38,60% no lado puncionado nos grupos I a V (p<0,05). Conclusões: No presente estudo, verificamos a obtenção de espermatozóides em todos os grupos até cinco punções. Todos os animais apresentaram alterações histológicas significativas dos epidídimos, quando comparados ao grupo controle, a partir da segunda punção, exceto na variável necrose. Somente nas variáveis infiltrado linfoplasmocitário e fibrose foram observadas efeito cumulativo das PESA. O estudo estereológico demonstrou aumento da densidade volume do tecido conjuntivo dos epidídimos provocado pelas punções / Abstract: Introduction: The treatment of male infertility had a great development in the last decades. The advent of assist reproductive techniques and specially the intra-cytoplasmic sperm injection (ICSI) has allowed the treatment of these patients otherwise considered infertile. Patients with obstructive and non-obstructive azoospermia, whose surgical reconstruction is not possible, can be submitted to retrieval spermatozoa procedures including microsurgical epididymal sperm aspiration (MESA), percutaneous epididymal sperm aspiration (PESA) testicular sperm extraction (TESE) and testicular sperm aspiration (TESA). Objectives: To verify the retrieval of viable spermatozoa within up to five percutaneous epididymal sperm aspirations and to evaluate the histological and stereological modifications in the rat epididymis after the procedures. Material and Methods: The pilot group consisted of four animals, two of them were used in the study about anatomy and histology of normal epididymis. The other two were used to verify the effects of the vasectomy. These procedures were performed through infra-umbilical laparotomy. The right side was standardized for the study group and the left for control. A total of 50 Wistar rats underwent vasectomy procedures and were distributed into five groups I to V, totalizing 10 animals each. In the group I, the animals underwent to one PESA procedure, II two, III three, IV four and V five. The epididymal punctures were done with 25G scalp in the caput after 30 days of the vasectomy and consecutively after 15 days of the previous puncture. The material extracted was suspended in HTF solution culture and analyzed in a Makler chamber. The epididymis were fixed in Bouin technique. Histological and stereological analyses were performed in the punctured epididymidis. Results: The number of retrieved spermatozoa was: mean 48.78 x 106 /ml, 37.55 x 106 /ml, 26.33 x 106 /ml, 33.90 x 106 /ml e 41.34 x 106 /ml, from group I to V. The histological analyses included evaluation of infiltration of lymphocytes and plasmocytes, granulomatous reaction, fibrosis and structural disorder; these alterations presented significant differences after the second puncture. The cumulative effect was observed only within the variables: lymphocytic and plasmocytic infiltrate and fibrosis. It was found differences in the groups I and II in comparison with III, IV and V. The stereological analyzes showed significant increase in connective tissue volume 21.56%, 27.60%, 35.67%, 37.56% and 38.60% from group I through V. Conclusions: In this study, it was performed retrieval of spermatozoa in all groups up to five punctures. All the animals presented histological alterations in the epididymis after the second puncture when compared to the control group, except necrosis, and only lymphocytic and plasmocytic infiltrate and fibrosis were shown as cumulative effects within the punctures. The stereological analyses showed increase of connective tissue volume that was caused by the punctures / Doutorado / Cirurgia / Doutor em Cirurgia

A number of genes have been associated with variation in human spermatogenesis related to fertility. One of these, the Deleted in Azoospermia (DAZ) gene, exists as copies on two chromosomes, 3 and Y. The autosomal copy, DAZ-like (DAZL), has one RNA recognition motif (RRM) and is homologous to the DAZL gene found throughout the vertebrate lineage. There are four copies of DAZ on the Y chromosome with a pair at each of two sites. One pair contains a single RRM and the other has three RRMs. Human DAZ is homologous to genes in old world primates and ape Y chromosomes. Both DAZ and DAZL bind messenger RNAs at U-rich sequences near the poly-A tail in a manner that facilitates translation. Both are expressed in spermatogonia during the transition from mitotic cellular expansion through meiotic chromosomal reduction and during spermiogenesis. This study examined genomic variation in DAZ and DAZL, including deletion of DAZ from individuals with various levels of sperm cell production and mutations of DAZL in male partners of infertile couples. Deletions in DAZ are not as common in azoospermic men from central Texas as compared to other reports. Single nucleotide polymorphisms (SNPs) were identified in anonymous infertility patients, but were not located in the exons of the RRM. Proteins produced from transcripts encoded by genes from human DAZL, DAZL with SNPs within and outside the RRM, and a DAZ with single RRM were identified. Binding activity of DAZL to mRNA was confirmed using a microarray method, and mRNA from human testes was screened to identify at least 1,313 mRNA potential targets for DAZL. These targets were involved in ribosome construction, pyruvate metabolism, cell cycle control, and proteasome function. Variations in binding of protein to a high and a low bound target mRNA were demonstrated between protein constructs of DAZL, DAZL with mutations, and DAZ. Binding of DAZL to mRNA was also confirmed using electrophoretic mobility shift assays. With materials and procedures developed during this study, comparisons of genetic variants of DAZ and DAZL can be performed to identify mechanisms responsible for structural and functional differences in control of spermatogenesis.

Gametogenesis is a highly complex process that requires stringent control of gene expression, in which translational regulation plays an essential role. Deleted in Azoospermia-like (DAZL) belongs to the DAZ family of RNA-binding proteins, which are restricted to germ cells, and regulate mRNA translation. Importantly, loss of function of these proteins results in infertility in both males and females in a wide variety of organisms. A model for the mechanism by which DAZL stimulates translation has been proposed based on work in Xenopus laevis (X. laevis) oocytes. In this model, DAZL functions by recruiting the translation initiation factor poly(A)-binding protein (PABP) to the 3’ untranslated region (UTR) of messenger RNAs. Simultaneous binding of PABP to Dazl and factors at the 5’ end confers a “closed-loop” mRNA conformation, which promotes translation initiation. To examine whether DAZL plays a similar role in mammals, co-expression of Dazl and PABP family members was investigated in fetal and adult mouse gonads. In contrast to X. laevis, mammals encode four cytoplasmic PABPs which share a similar domain organisation: PABP1, tPABP, ePABP and PABP4, of which PABP1 and PABP4 appear to be expressed in a wide range of tissues. Immunohistochemistry revealed that Dazl, Pabp1 and Pabp4 are all expressed in primordial germ cells (PGCs) but these show different expression patterns following germ cell sex differentiation. In adult testes Dazl is expressed in spermatogonia and spermatocytes, coinciding with the peak of Pabp4 expression. In contrast, the peak of Pabp1 expression occurs later than that of Dazl, with these proteins only being co-expressed in late pachytene and secondary spermatocyte phases. In adult ovaries, Pabp1, Pabp4 and Dazl are all expressed in the oocytes of primordial and primary follicles. Since both PABP family members are co-expressed with Dazl, the ability of DAZL to interact with PABP1 and PABP4 was investigated in vitro and in vivo. Surprisingly, these studies showed that DAZL discriminates between different PABP family members, only interacting with PABP1, providing the first report of a PABP-specific protein partner. Several putative DAZL mutations have been identified in patients with impaired fertility. Two of these mutations, I37A and R115G, are located in the RNA recognition motif (RRM), a domain which is found in many RNA-binding proteins and mediates both RNA and protein interactions. Thus, the role of these mutations in the ability of DAZL to stimulate translation was investigated. To this end, a translational target of human DAZL (hDAZL) was sought. The 3’UTR of growth differentiation factor 9 (hGDF9) mRNA was found to confer regulation by hDAZL and thus the ability of mutant DAZLs to stimulate reporter mRNAs containing this 3’UTR was examined. This revealed that both mutations compromised the ability of hDAZL to stimulate hGDF9 translation, suggesting a causative effect. These results were further confirmed in assays in which hDAZL is artificially tethered to mRNAs. The ability of mutant hDAZLs to stimulate translation in this assay was compromised suggesting that loss of function is, at least in part, due to impaired protein-protein interactions rather than altered RNA-binding. This work provides insights into the molecular mechanism by which DAZL stimulates the translation of specific mRNAs during mammalian gametogenesis and provides evidence that this function may play an important physiological role in human reproduction.

No description available.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13165号 / 論医博第2152号 / 新制||医||1029(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 篠原 隆司, 教授 宮本 享, 教授 近藤 玄 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

The full text of the thesis is currently restricted. / The full text will be available at the end of the embargo period: 1st Nov 2021

A infertilidade é um problema de saúde pública com um significativo impacto social, econômico e psicológico. Em todo o mundo, a incidência da infertilidade entre a população geral é estimada em 10-15%. Cerca de 50% da infertilidade dos casais são de origem masculina. Em mais da metade dos homens inférteis, a causa da infertilidade é desconhecida (idiopática). Etiologicamente, a infertilidade masculina apresenta causas genéticas e não genéticas. Dentre as causas genéticas mais conhecidas temos mutação do receptor de andrógenos, mutação do gene regulador da condutibilidade transmembrana da fibrose cística (CFTR), anomalias cromossômicas clássicas, anomalias meióticas, microdeleções do cromossomo Y, etc. As anomalias cromossômicas são encontradas com muito mais frequência em homens inférteis, com uma incidência de 4-16% em relação à incidência de 0,4% na população fértil. Estudos mostram que as CNVs também podem estar relacionadas com a infertilidade masculina, especificamente com a falha na espermatogênese. CNVs encontradas tanto no cromossomo Y quanto nos cromossomos autossômicos também foram associadas a possíveis falhas na espermatogênese. Um outro fator que também pode estar envolvido com a infertilidade masculina é a expressão desregulada dos miRNAs. O presente trabalho teve como objetivo promover a análise em larga escala da distribuição de CNVs e do perfil transcricional dos miRNAs em amostras de biopsias testiculares de paciente com azoospermia. Para o estudo das CNVs nós utilizamos a metodologia do CytoScan HDTM da Affymetrix. O perfil transcricional de miRNAs nos indivíduos estudados foi avaliado por meio da tecnologia de microarranjos também da plataforma Affymetrix. Para estas analises montamos dois grupos de estudo (Parada de Maturação (MA) de Células Germinativas e Síndrome de Células Sertoli Only (SCOS)) e um grupo controle (azoospermia obstrutiva e espermatogênese normal). Através das análises das CNVs nós encontramos 94 CNVs nos cromossomos autossômicos e sexuais, 35 (37%) CNVs foram classificadas como benignas, 24 (23%) como potencialmente benignas, sete CNVs (7,4%) como patogênicas e sete foram classificadas como potencialmente patogênica. Todas as CNVs classificadas como patogênica estão presentes no cromossomo Y, cinco CNVs são do tipo duplicação e duas do tipo deleção. A CNV do tipo duplicação foi encontrada no paciente MA e a CNV do tipo deleção foi encontrada no paciente SCOS. As CNVs se sobrepõem e quando analisadas em conjunto (formando uma única CNV de cada condição) elas apresentam um tamanho parecido. Estas CNVs apresentam genes envolvidos na espermatogênese. As CNVs classificadas como potencialmente patogênicas estavam presentes nos cromossomos autossômicos e cromossomo X. Nestas CNVs estavam presentes genes que foram associados com a falha na espermatogênese. A análise da expressão dos miRNAs revelou um perfil transicional muito mais alterado nos pacientes com SCOS. As duas condições apresentaram miRNAs exclusivos, mas também compartilharam: 30 miRNAs. Nós identificamos duas famílias de miRNAs (miR449 e miR34) diferencialmente expressos nas duas condições e que apresentam expressão preferencial no testículo. Nossos resultados mostram que alterações no número de copias (CNVs) no cromossomo Y levam a infertilidade masculina e CNVs nos cromossomos autossômicos e X podem levar a infertilidade masculina. As alterações do tipo deleção podem levar a uma falha na espermatogênese maior que as alterações do tipo duplicação. A expressão diferencial dos miRNAs em tecido testicular de pacientes com diferenças histopatológicas (SCOS e MA) apresentam um padrão de expressão de miRNAs diferentes devido ao tipo de células germinativas que eles apresentam no tecido epitelial do testículo. / Infertility is a public health problem with significant social, economic and psychological impact. Worldwide, the incidence of infertility in the general population is estimated at 10- 15%. Approximately 50% of infertility of couples is of male origin. In more than half of infertile men, the cause of infertility is unknown (idiopathic). Etiologically, male infertility has genetic and non-genetic causes. Among the best known genetic causes we found the mutation of the androgen receptor, the cystic fibrosis transmembrane conductance regulator (CFTR), classic chromosomal abnormalities, meiotic abnormalities and microdeletions of the Y chromosome. Chromosomal abnormalities are found much more frequently in infertile men, with an incidence of 4-16% in the incidence of 0.4% in the fertile population. Studies show that CNVs can also be related to male infertility, specifically in the failure of spermatogenesis. CNVs found in both the Y and autosomes chromosomes were also associated with possible failures in spermatogenesis. Another factor that may also be involved in male infertility is the deregulated expression of miRNAs. This work aimed to promote the analysis of large-scale distribution of CNVs and the transcriptional profile of miRNAs in testicular biopsy samples from patients with azoospermia. For the study of CNV we used the CytoScan HDTM Affymetrix methodology and the transcriptional profile of miRNAs in the samples was assessed by means of microarray technology from Affymetrix platform. For these analyzes we set up two study groups (Stop Maturation (MA) of Germ Cells and Sertoli Cell Only Syndrome (SCOS)) and compared them to a control group (obstructive azoospermia, normal spermatogenesis). Through analysis of CNVs, we found 94 CNVs in sexual and autosomes chromosomes, 35 (37%) were classified as benign CNVs, 24 (23%) as a potentially benign seven CNVs (7.4%) as pathogenic and 7 were classified as potentially pathogenic. All CNVs classified as pathogenic are present on the Y chromosome, five CNVs are of duplication type and two are deletion type. The duplication type CNV was found in MA patients and deletion type CNV was found in SCOS patient. We identified that CNVs overlap and when analyzed jointed - as a single CNV of each condition - they have a similar size. These CNVs have genes involved in spermatogenesis. CNVs classified as potentially pathogenic were present in autosomes and in the X chromosome. In these CNVs were present genes that were associated with failure in spermatogenesis. The analysis of the expression of miRNAs revealed a transitional profile much more altered in patients with SCOS. The two conditions presented exclusive miRNAs, but shared 30 miRNAs differentially expressed when compared to the control group. We identify two families of miRNAs (miR449 and miR34) which exhibit preferential expression in testis as differentially expressed in both conditions. Our results show that changes in the number of copies (CNVs) on the Y chromosome lead to male infertility and CNVs in autosomes and X chromosomes may lead to male infertility. The deletion type changes can lead to a failure of spermatogenesis greater than the duplication type changes. The differential expression of miRNAs in patients with testicular tissue histopathologic differences (SCOS and MA) has a different pattern of miRNA expression due to the type of germ cells they present in epithelial tissue of the testis.

A infertilidade é um problema de saúde pública com um significativo impacto social, econômico e psicológico. Em todo o mundo, a incidência da infertilidade entre a população geral é estimada em 10-15%. Cerca de 50% da infertilidade dos casais são de origem masculina. Em mais da metade dos homens inférteis, a causa da infertilidade é desconhecida (idiopática). Etiologicamente, a infertilidade masculina apresenta causas genéticas e não genéticas. Dentre as causas genéticas mais conhecidas temos mutação do receptor de andrógenos, mutação do gene regulador da condutibilidade transmembrana da fibrose cística (CFTR), anomalias cromossômicas clássicas, anomalias meióticas, microdeleções do cromossomo Y, etc. As anomalias cromossômicas são encontradas com muito mais frequência em homens inférteis, com uma incidência de 4-16% em relação à incidência de 0,4% na população fértil. Estudos mostram que as CNVs também podem estar relacionadas com a infertilidade masculina, especificamente com a falha na espermatogênese. CNVs encontradas tanto no cromossomo Y quanto nos cromossomos autossômicos também foram associadas a possíveis falhas na espermatogênese. Um outro fator que também pode estar envolvido com a infertilidade masculina é a expressão desregulada dos miRNAs. O presente trabalho teve como objetivo promover a análise em larga escala da distribuição de CNVs e do perfil transcricional dos miRNAs em amostras de biopsias testiculares de paciente com azoospermia. Para o estudo das CNVs nós utilizamos a metodologia do CytoScan HDTM da Affymetrix. O perfil transcricional de miRNAs nos indivíduos estudados foi avaliado por meio da tecnologia de microarranjos também da plataforma Affymetrix. Para estas analises montamos dois grupos de estudo (Parada de Maturação (MA) de Células Germinativas e Síndrome de Células Sertoli Only (SCOS)) e um grupo controle (azoospermia obstrutiva e espermatogênese normal). Através das análises das CNVs nós encontramos 94 CNVs nos cromossomos autossômicos e sexuais, 35 (37%) CNVs foram classificadas como benignas, 24 (23%) como potencialmente benignas, sete CNVs (7,4%) como patogênicas e sete foram classificadas como potencialmente patogênica. Todas as CNVs classificadas como patogênica estão presentes no cromossomo Y, cinco CNVs são do tipo duplicação e duas do tipo deleção. A CNV do tipo duplicação foi encontrada no paciente MA e a CNV do tipo deleção foi encontrada no paciente SCOS. As CNVs se sobrepõem e quando analisadas em conjunto (formando uma única CNV de cada condição) elas apresentam um tamanho parecido. Estas CNVs apresentam genes envolvidos na espermatogênese. As CNVs classificadas como potencialmente patogênicas estavam presentes nos cromossomos autossômicos e cromossomo X. Nestas CNVs estavam presentes genes que foram associados com a falha na espermatogênese. A análise da expressão dos miRNAs revelou um perfil transicional muito mais alterado nos pacientes com SCOS. As duas condições apresentaram miRNAs exclusivos, mas também compartilharam: 30 miRNAs. Nós identificamos duas famílias de miRNAs (miR449 e miR34) diferencialmente expressos nas duas condições e que apresentam expressão preferencial no testículo. Nossos resultados mostram que alterações no número de copias (CNVs) no cromossomo Y levam a infertilidade masculina e CNVs nos cromossomos autossômicos e X podem levar a infertilidade masculina. As alterações do tipo deleção podem levar a uma falha na espermatogênese maior que as alterações do tipo duplicação. A expressão diferencial dos miRNAs em tecido testicular de pacientes com diferenças histopatológicas (SCOS e MA) apresentam um padrão de expressão de miRNAs diferentes devido ao tipo de células germinativas que eles apresentam no tecido epitelial do testículo. / Infertility is a public health problem with significant social, economic and psychological impact. Worldwide, the incidence of infertility in the general population is estimated at 10- 15%. Approximately 50% of infertility of couples is of male origin. In more than half of infertile men, the cause of infertility is unknown (idiopathic). Etiologically, male infertility has genetic and non-genetic causes. Among the best known genetic causes we found the mutation of the androgen receptor, the cystic fibrosis transmembrane conductance regulator (CFTR), classic chromosomal abnormalities, meiotic abnormalities and microdeletions of the Y chromosome. Chromosomal abnormalities are found much more frequently in infertile men, with an incidence of 4-16% in the incidence of 0.4% in the fertile population. Studies show that CNVs can also be related to male infertility, specifically in the failure of spermatogenesis. CNVs found in both the Y and autosomes chromosomes were also associated with possible failures in spermatogenesis. Another factor that may also be involved in male infertility is the deregulated expression of miRNAs. This work aimed to promote the analysis of large-scale distribution of CNVs and the transcriptional profile of miRNAs in testicular biopsy samples from patients with azoospermia. For the study of CNV we used the CytoScan HDTM Affymetrix methodology and the transcriptional profile of miRNAs in the samples was assessed by means of microarray technology from Affymetrix platform. For these analyzes we set up two study groups (Stop Maturation (MA) of Germ Cells and Sertoli Cell Only Syndrome (SCOS)) and compared them to a control group (obstructive azoospermia, normal spermatogenesis). Through analysis of CNVs, we found 94 CNVs in sexual and autosomes chromosomes, 35 (37%) were classified as benign CNVs, 24 (23%) as a potentially benign seven CNVs (7.4%) as pathogenic and 7 were classified as potentially pathogenic. All CNVs classified as pathogenic are present on the Y chromosome, five CNVs are of duplication type and two are deletion type. The duplication type CNV was found in MA patients and deletion type CNV was found in SCOS patient. We identified that CNVs overlap and when analyzed jointed - as a single CNV of each condition - they have a similar size. These CNVs have genes involved in spermatogenesis. CNVs classified as potentially pathogenic were present in autosomes and in the X chromosome. In these CNVs were present genes that were associated with failure in spermatogenesis. The analysis of the expression of miRNAs revealed a transitional profile much more altered in patients with SCOS. The two conditions presented exclusive miRNAs, but shared 30 miRNAs differentially expressed when compared to the control group. We identify two families of miRNAs (miR449 and miR34) which exhibit preferential expression in testis as differentially expressed in both conditions. Our results show that changes in the number of copies (CNVs) on the Y chromosome lead to male infertility and CNVs in autosomes and X chromosomes may lead to male infertility. The deletion type changes can lead to a failure of spermatogenesis greater than the duplication type changes. The differential expression of miRNAs in patients with testicular tissue histopathologic differences (SCOS and MA) has a different pattern of miRNA expression due to the type of germ cells they present in epithelial tissue of the testis.