Microdeletions and vertical transmission of the Y-chromosome azoospermia factor region / 亚洲男科学杂志(英文版)

Spermatogenesis is regulated by several Y chromosome-specific genes located in a specific region of the long arm of the Y chromosome, the azoospermia factor region (AZF). AZF microdeletions are the main structural chromosomal abnormalities that cause male infertility. Assisted reproductive technology (ART) has been used to overcome natural fertilization barriers, allowing infertile couples to have children. However, these techniques increase the risk of vertical transmission of genetic defects. Despite widespread awareness of AZF microdeletions, the occurrence of de novo deletions and overexpression, as well as the expansion of AZF microdeletion vertical transmission, remains unknown. This review summarizes the mechanism of AZF microdeletion and the function of the candidate genes in the AZF region and their corresponding clinical phenotypes. Moreover, vertical transmission cases of AZF microdeletions, the impact of vertical inheritance on male fertility, and the prospective direction of research in this field are also outlined.

Incidence and genetic reproductive characteristics of AZFc microdeletion among patients with azoospermia or severe oligospermia / 中华医学遗传学杂志

OBJECTIVE@#To explore the incidence of azoospermia factor c (AZFc) microdeletion among patients with azoospermia or severe oligospermia, its association with sex hormone/chromosomal karyotype, and its effect on the outcome of pregnancy following intracytoplasmic sperm injection (ICSI) treatment.@*METHODS@#A total of 1 364 males with azoospermia or severe oligospermia who presented at the Affiliated Maternity and Child Health Care Hospital of Jiaxing College between 2013 and 2020 were subjected to AZF microdeletion and chromosome karyotyping analysis. The level of reproductive hormones in patients with AZFc deletions was compared with those of control groups A (with normal sperm indices) and B (azoospermia or severe oligospermia without AZFc microdeletion). The outcome of pregnancies for the AZFc-ICSI couples was compared with that of the control groups in regard to fertilization rate, superior embryo rate and clinical pregnancy rate.@*RESULTS@#A total of 51 patients were found to harbor AZFc microdeletion, which yielded a detection rate of 3.74%. Seven patients also had chromosomal aberrations. Compared with control group A, patients with AZFc deletion had higher levels of PRL, FSH and LH (P < 0.05), whilst compared with control group B, only the PRL and FSH were increased (P < 0.05). Twenty two AZFc couples underwent ICSI treatment, and no significant difference was found in the rate of superior embryos and clinical pregnancy between the AZFc-ICSI couples and the control group (P > 0.05).@*CONCLUSION@#The incidence of AZFc microdeletion was 3.74% among patients with azoospermia or severe oligospermia. AZFc microdeletion was associated with chromosomal aberrations and increased levels of PRL, FSH and LH, but did not affect the clinical pregnancy rate after ICSI treatment.

Analysis of copy number variation in AZF region of Y chromosome in patients with spermatogenic failure / 中华医学遗传学杂志

OBJECTIVE@#To explore the characteristics of copy number variation (CNV) within the Y chromosome azoospermia factor (AZF) region in patients with spermatogenesis disorders in the Shenzhen area.@*METHODS@#A total of 123 patients with spermatogenesis disorders who had visited Shenzhen People's Hospital from January 2016 to October 2022 (including 73 patients with azoospermia and 50 patients with oligozoospermia) and 100 normal semen males were selected as the study subjects. The AZF region was detected with multiplex ligation-dependent probe amplification (MLPA), and the correlation between the CNV in the AZF region and spermatogenesis disorders was analyzed using the chi-square test or Fisher's exact test.@*RESULTS@#19 CNV were detected among 53 patients from the 223 samples, including 20 cases (27.40%, 20/73) from the azoospermia group, 19 cases (38%, 19/50) from the oligozoospermia group, and 14 cases (14%, 14/100) from the normal control group. In the azoospermia, oligozoospermia, and normal control groups, the detection rates for CNV related to the AZFa region (including AZFab and AZFabc) were 5.48% (4/73), 2.00% (1/50), and 0 (0/100), respectively. The detection rates for the AZFb region (including the AZFbc region) were 6.85% (5/73), 0 (0/50), and 0 (0/100), respectively. The detection rates for gr/gr deletions in the AZFc region were 2.74% (2/73), 6.00% (3/50), and 9.00% (9/100), respectively, and those for b2/b4 deletions in the AZFc region were 2.74% (2/73), 10.00% (5/50), and 0 (0/100), respectively. The detection rates for complex rearrangements in the AZFc region were 6.85% (5/73), 18.00% (9/50), and 3.00% (3/100), respectively. Statistical analysis showed no significant difference in the detection rate of gr/gr deletions between the three groups (Fisher's Exact Test value = 2.712, P = 0.249); the differences in the detection rate of b2/b4 deletions between the three groups were statistically significant (Fisher's Exact Test value = 9.489, P = 0.002); the differences in the detection rate of complex rearrangements in the AZFc region between the three groups were statistically significant (Fisher's Exact Test value = 9.493, P = 0.006). In this study, a rare AZFa region ARSLP1 gene deletion (involving SY86 deletion) was detected in a patient with oligozoospermia.@*CONCLUSION@#CNV in the AZFa and AZFb regions have a severe impact on spermatogenesis, but partial deletion in the AZFa region (ARSLP1 gene deletion) has a minor impact on spermatogenesis. The b2/b4 deletion and complex rearrangement in the AZFc region may be risk factors for male infertility. The gr/gr deletion may not serve as a risk factor for male infertility in the Shenzhen area.

From azoospermia to macrozoospermia, a phenotypic continuum due to mutations in the ZMYND15 gene / 亚洲男科学杂志(英文版)

Thanks to tremendous advances in sequencing technologies and in particular to whole exome sequencing (WES), many genes have now been linked to severe sperm defects. A precise genetic diagnosis is obtained for a minority of patients and only for the most severe defects like azoospermia or macrozoospermia which is very often due to defects in the aurora kinase C (AURKC gene. Here, we studied a subject with a severe oligozoospermia and a phenotypic diagnosis of macrozoospermia. AURKC analysis did not reveal any deleterious variant. WES was then initiated which permitted to identify a homozygous loss of function variant in the zinc finger MYND-type containing 15 (ZMYND15 gene. ZMYND15 has been described to serve as a switch for haploid gene expression, and mice devoid of ZMYND15 were shown to be sterile due to nonobstructive azoospermia (NOA). In man, ZMYND15 has been associated with NOA and severe oligozoospermia. We confirm here that the presence of a bi-allelic ZMYND15 variant induces a severe oligozoospermia. In addition, we show that severe oligozoospermia can be associated macrozoospermia, and that a phenotypic misdiagnosis is possible, potentially delaying the genetic diagnosis. In conclusion, genetic defects in ZMYND15 can induce complete NOA or severe oligozoospermia associated with a very severe teratozoospermia. In our experience, severe oligozoospermia is often associated with severe teratozoospermia and can sometimes be misinterpreted as macrozoospermia or globozoospermia. In these instances, specific AURKC or dpy-19 like 2 (DPY19L2) diagnosis is usually negative and we recommend the direct use of a pan-genomic techniques such as WES.

Investigation of the genetic etiology in male infertility with apparently balanced chromosomal structural rearrangements by genome sequencing / 亚洲男科学杂志(英文版)

Apparently balanced chromosomal structural rearrangements are known to cause male infertility and account for approximately 1% of azoospermia or severe oligospermia. However, the underlying mechanisms of pathogenesis and etiologies are still largely unknown. Herein, we investigated apparently balanced interchromosomal structural rearrangements in six cases with azoospermia/severe oligospermia to comprehensively identify and delineate cryptic structural rearrangements and the related copy number variants. In addition, high read-depth genome sequencing (GS) (30-fold) was performed to investigate point mutations causative of male infertility. Mate-pair GS (4-fold) revealed additional structural rearrangements and/or copy number changes in 5 of 6 cases and detected a total of 48 rearrangements. Overall, the breakpoints caused truncations of 30 RefSeq genes, five of which were associated with spermatogenesis. Furthermore, the breakpoints disrupted 43 topological-associated domains. Direct disruptions or potential dysregulations of genes, which play potential roles in male germ cell development, apoptosis, and spermatogenesis, were found in all cases (n = 6). In addition, high read-depth GS detected dual molecular findings in case MI6, involving a complex rearrangement and two point mutations in the gene DNAH1. Overall, our study provided the molecular characteristics of apparently balanced interchromosomal structural rearrangements in patients with male infertility. We demonstrated the complexity of chromosomal structural rearrangements, potential gene disruptions/dysregulation and single-gene mutations could be the contributing mechanisms underlie male infertility.

MBOAT1 homozygous missense variant causes nonobstructive azoospermia / 亚洲男科学杂志(英文版)

Nonobstructive azoospermia (NOA) is a common cause of infertility and is defined as the complete absence of sperm in ejaculation due to defective spermatogenesis. The aim of this study was to identify the genetic etiology of NOA in an infertile male from a Chinese consanguineous family. A homozygous missense variant of the membrane-bound O-acyltransferase domain-containing 1 (MBOAT1) gene (c.770C>T, p.Thr257Met) was found by whole-exome sequencing (WES). Bioinformatic analysis also showed that this variant was a pathogenic variant and that the amino acid residue in MBOAT1 was highly conserved in mammals. Quantitative polymerase chain reaction (Q-PCR) analysis showed that the mRNA level of MBOAT1 in the patient was 22.0% lower than that in his father. Furthermore, we screened variants of MBOAT1 in a broader population and found an additional homozygous variant of the MBOAT1 gene in 123 infertile men. Our data identified homozygous variants of the MBOAT1 gene associated with male infertility. This study will provide new insights for researchers to understand the molecular mechanisms of male infertility and will help clinicians make accurate diagnoses.

Rescue of male infertility through correcting a genetic mutation causing meiotic arrest in spermatogonial stem cells / 亚洲男科学杂志(英文版)

Azoospermia patients who carry a monogenetic mutation that causes meiotic arrest may have their biological child through genetic correction in spermatogonial stem cells (SSCs). However, such therapy for infertility has not been experimentally investigated yet. In this study, a mouse model with an X-linked testis-expressed 11 (TEX11) mutation (Tex11

Altered microRNA profiles of testicular biopsies from patients with nonobstructive azoospermia / 亚洲男科学杂志(英文版)

Many studies have shown that microRNAs (miRNAs) play vital roles during the spermatogenesis. However, little is known about the altered miRNA profiles of testicular tissues in nonobstructive azoospermia (NOA). Using microarray technology, the miRNA expression profiles of testicular biopsies from patients with NOA and of normal testicular tissues were determined. Bioinformatics analyses were conducted to predict the enriched biological processes and functions of identified miRNAs. The microarray data were validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), the results of which were then validated with a larger sample size. Correlations between the miRNA expression levels and clinical characteristics were analyzed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic ability of miRNAs for azoospermia. Hierarchical clustering showed that 129 miRNAs were significantly differentially expressed between the NOA and control groups. Bioinformatics analysis indicated that the differentially expressed miRNAs were involved in spermatogenesis, cell cycle, and mitotic prometaphase. In the subsequent qRT-PCR assays, the selected miRNA expression levels were consistent with the microarray results, and similar validated results were obtained with a larger sample size. Some clinical characteristics were significantly associated with the expression of certain miRNAs. In particular, we identified a combination of two miRNAs (miR-10b-3p and miR-34b-5p) that could serve as a predictive biomarker of azoospermia. This study provides altered miRNA profiles of testicular biopsies from NOA patients and examines the roles of miRNAs in spermatogenesis. These profiles may be useful for predicting and diagnosing the presence of testicular sperm in individuals with azoospermia.

The association of stromal antigen 3 (STAG3) sequence variations with spermatogenic impairment in the male Korean population / 亚洲男科学杂志(英文版)

The stromal antigen 3 (STAG3) gene, encoding a meiosis-specific cohesin component, is a strong candidate for causing male infertility, but little is known about this gene so far. We identified STAG3 in patients with nonobstructive azoospermia (NOA) and normozoospermia in the Korean population. The coding regions and their intron boundaries of STAG3 were identified in 120 Korean men with spermatogenic impairments and 245 normal controls by using direct sequencing and haplotype analysis. A total of 30 sequence variations were identified in this study. Of the total, seven were exonic variants, 18 were intronic variants, one was in the 5'-UTR, and four were in the 3'-UTR. Pathogenic variations that directly caused NOA were not identified. However, two variants, c.3669+35C>G (rs1727130) and +198A>T (rs1052482), showed significant differences in the frequency between the patient and control groups (P = 0.021, odds ratio [OR]: 1.79, 95% confidence interval [CI]: 1.098-2.918) and were tightly linked in the linkage disequilibrium (LD) block. When pmir-rs1052482A was cotransfected with miR-3162-5p, there was a substantial decrease in luciferase activity, compared with pmir-rs1052482T. This result suggests that rs1052482 was located within a binding site of miR-3162-5p in the STAG3 3'-UTR, and the minor allele, the rs1052482T polymorphism, might offset inhibition by miR-3162-5p. We are the first to identify a total of 30 single-nucleotide variations (SNVs) of STAG3 gene in the Korean population. We found that two SNVs (rs1727130 and rs1052482) located in the 3'-UTR region may be associated with the NOA phenotype. Our findings contribute to understanding male infertility with spermatogenic impairment.

Los ARNs no codificantes largos y su vinculación con las patologías testiculares / Long non-coding RNAs and their involvement in testicular pathologies / RNAs longos não-codificantes e sua ligação com patologias testiculares

Si bien la porción del genoma destinada a la síntesis de proteínas es muy pequeña, actualmente se sabe que casi todo el genoma se expresa bajo forma de ARNs no codificantes. Entre dichos ARNs se encuentran los ARNs no codificantes largos (lncRNAs). Aunque los lncRNAs han sido muy poco estudiados, recientemente han comenzado a centrar la atención de los investigadores, al descubrirse que los mismos pueden desempeñar diversas funciones en la regulación de la expresión génica. Además, su vinculación con patologías ha comenzado a ser puesta de manifiesto. Curiosamente, la cantidad de lncRNAs presentes en el testículo es abrumadoramente mayor que en cualquier otro órgano o tejido estudiado. Los perfiles de expresión de estos lncRNAs varían significativamente a lo largo de la espermatogénesis, y algunas evidencias sugieren que al menos algunos de ellos podrían participar en el proceso de formación de células germinales masculinas. No obstante, el conocimiento sobre el tema es aún muy escaso. En este trabajo revisamos la información disponible sobre la expresión de lncRNAs en el testículo y sus posibles funciones. Asimismo, analizamos algunos ejemplos que ilustran la participación de lncRNAs en el desarrollo de patologías como la infertilidad y el cáncer testicular.

Although the portion of the genome devoted to protein synthesis is very small, it is now known that almost the entire genome is expressed as non-coding RNAs. Among them, there are long noncoding RNAs (lncRNAs). Despite that lncRNAs have been very poorly studied, they have recently started to focus the attention of researchers, as it has been found out that lncRNAs can perform diverse functions in the regulation of gene expression. Besides, their involvement in pathologies is being revealed. Intriguingly, the amount of lncRNAs in the testis is overwhelmingly higher than in any other analyzed organ or tissue. LncRNA expression profiles significantly vary along spermatogenesis, and some evidence suggests that at least some of them could participate in the formation of male germ cells. However, knowledge on the subject is still very scarce. In this work we review the available information on the expression of lncRNAs in testis and their possible roles. We also analyze some examples that illustrate the participation of lncRNAs in the development of pathologies such as infertility and testicular cancer.

Embora a porção do genoma usada para a síntese proteica seja muito pequena, sabe-se agora que quase todo o genoma é expresso na forma de RNAs não-codificantes. Entre esses RNAs estão os longos RNAs não codificantes (lncRNAs). Embora os lncRNAs tenham sido pouco estudados, eles recentemente começaram a focar a atenção dos pesquisadores, ao descobrirem que podem desempenhar diversas funções na regulação da expressão gênica. Além disso, sua ligação com as patologias começou a ser revelada. Curiosamente, a quantidade de lncRNAs presentes nos testículos é esmagadoramente maior do que em qualquer outro órgão ou tecido estudado. Os perfis de expressão destes lncRNAs variam significativamente ao longo da espermatogênese, e algumas evidências sugerem que pelo menos alguns deles poderiam participar no processo de formação de células germinativas masculinas. No entanto, o conhecimento sobre o assunto ainda é muito escasso. Neste trabalho, revisamos as informações disponíveis sobre a expressão de lncRNAs no testículo e suas possíveis funções. Também analisamos alguns exemplos que ilustram a participação dos lncRNAs no desenvolvimento de patologias como infertilidade e câncer testicular.

Altered PIWI-LIKE 1 and PIWI-LIKE 2 mRNA expression in ejaculated spermatozoa of men with impaired sperm characteristics / 亚洲男科学杂志(英文版)

In about half the cases of involuntary childlessness, a male infertility factor is involved. The PIWI-LIKE genes, a subclade of the Argonaute protein family, are involved in RNA silencing and transposon control in the germline. Knockout of murine Piwi-like 1 and 2 homologs results in complete infertility in males. The aim of this study was to analyze whether the mRNA expression of human PIWI-LIKE 1-4 genes is altered in ejaculated spermatozoa of men with impaired sperm characteristics. Ninety male participants were included in the study, among which 47 were with normozoospermia, 36 with impaired semen characteristics according to the World Health Organization (WHO) manual, 5th edition, and 7 with azoospermia serving as negative control for the PIWI-LIKE 1-4 mRNA expression in somatic cells in the ejaculate. PIWI-LIKE 1-4 mRNA expression in the ejaculated spermatozoa of the participants was measured by quantitative real-time PCR. In nonazoospermic men, PIWI-LIKE 1-4 mRNA was measurable in ejaculated spermatozoa in different proportions. PIWI-LIKE 1 (100.0%) and PIWI-LIKE 2 (49.4%) were more frequently expressed than PIWI-LIKE 3 (9.6%) and PIWI-LIKE 4 (15.7%). Furthermore, a decreased PIWI-LIKE 2 mRNA expression showed a significant correlation with a decreased sperm count (P = 0.022) and an increased PIWI-LIKE 1 mRNA expression with a decreased progressive motility (P = 0.048). PIWI-LIKE 1 and PIWI-LIKE 2 mRNA expression exhibited a significant association with impaired sperm characteristics and may be a useful candidate for the evaluation of the impact of PIWI-LIKE 1-4 mRNA expression on male infertility.

Analysis of chromosome in 1 324 patients with oligozoospermia or azoosperm / 北京大学学报(医学版)

OBJECTIVE@#To explore the incidience of chromosome abnormality of the patients with oligozoospermia or azoospermia and male infertility, to discuss the relationship between the quantitative and structural abnormality of chromosome and to lay the foundation for the clinical diagnosis and consultation.@*METHODS@#A retrospective analysis was conducted from January 1, 2015 to May 1, 2016, in the Center for Reproduction Medicine, the Second Hospital of Jilin University, with male reproductive abnormalities history excluded. In the study, 1 324 cases were included with 448 cases of azoospermia and 876 cases of oligozoospermia. All the patients through ultrasound examination, color Doppler ultrasonography, the seminal plasma Zn determination, their hormone level determination, chromosome karyotype (the perinatal blood samples were obtained from the 1 324 patients with oligozoospermia or azoospermia for lymphocyte culture, then chromosomal specimens were prepared, G-banding analyses combined with clinical data were used to statistically analyze the incidence of chromosomal abnormality), Y chromosome azoospermia factor [PCR technique was used to detect SY157 locus, SY254 locus, and SY255 locus in male Y chromosome azoospermia factor (AZF) gene of the patients with oligozoospermia or azoospermia]. The relationship between chromosome abnormalities and oligozoospermia or azoospermia were analyzed.@*RESULTS@#Among the 876 cases of oligospermia patients, 78 cases were chromosome number abnormality and chromosomal structural abnormality, the abnormal number of sex chromosomes in 22 cases, and sex chromosomes and chromosome structural abnormalities in 56 cases; in the 448 cases of azoospermia patients, 91 cases were chromosomal structural abnormality and chromosome number abnormality, of them, 78 cases were of abnormal number of sex chromosomes, and 13 cases were of abnormal structure. In addition, 137 cases were of chromosome polymorphism in all the 1 324 patients, The incidence of Y chromosome abnormality in azoospermatism was higher than that of the 43 patients with Y chromosome AZF microdeletion. In addition, the asthenospermia and recurrent spontaneous abortion were closely related to Y chromosome abnormality and the chromosome translocations and inversions.@*CONCLUSION@#Oligozoospermia and azoospermia patients with abnormal chromosome karyotype have high incidence rate, and chromosome karyotype analyses were carried out on it, which is conducive to clinical diagnosis for the patients with abnormal chromosome karyotype. There is a close relationship between male infertility and abnormal karyotype. It is conducive to clinical diagnosis for the patients with infertility through chromosome karyotye analysis, which also provides evidence for genetic counseling.

prevalence of Y chromosome microdeletions in iranian infertile men with azoospermia and severe oligospermia

Objective: Microdeletions of the Y chromosome long arm are the most common molecular genetic causes of severe infertility in men. They affect three regions including azoospermia factors [AZFa, AZFb and AZFc], which contain various genes involved in spermatogenesis. The aim of the present study was to reveal the patterns of Y chromosome microdeletions in Iranian infertile men referred to Royan Institute with azoospermia/ severe oligospermia

Materials and Methods: Through a cross-sectional study, 1885 infertile men referred to Royan Institute with azoospermia/severe oligospermia were examined for Y chromosome microdeletions from March 2012 to March 2014. We determined microdeletions of the Y chromosome in the AZFa, AZFb and AZFc regions using multiplex Polymerase chain reaction and six different Sequence-Tagged Site [STS] markers

Results: Among the 1885 infertile men, we determined 99 cases of Y chromosome microdeletions [5.2%]. Among 99 cases, AZFc microdeletions were found in 70 cases [70.7%]; AZFb microdeletions in 5 cases [5%]; and AZFa microdeletions in only 3 cases [3%]. AZFbc microdeletions were detected in 18 cases [18.1%] and AZFabc microdeletions in 3 cases [3%]

Conclusion: Based on these data, our results are in agreement with similar studies from other regions of the world as well as two other recent studies from Iran which have mostly reported a frequency of less than 10% for Y chromosome microdeletions

Screening of two neighboring CFTR mutations in Iranian infertile men with non-obstructive azoospermia

The genetic association between cystic fibrosis transmembrane conductance regulator [CFTR] gene mutations and male infertility due to congenital bilateral absence of vas deferens [CBAVD] is well established. Mutant CFTR, however may also be involved in the etiology of male infertility in non-CBAVD cases. The present study was conducted to estimate the frequency of DELTA I507 and DELTA F508 CFTR gene mutations in Iranian infertile males. We undertook the first study of association between these CFTR mutations and non-obstructive azoospermia in Iran. In this case-control study, 100 fertile healthy fathers and 100 non-obstructive azoospermia's men were recruited from Isfahan Infertility Center [IIC] and Sari Saint Mary's Infertility Center, between 2008 and 2009. Screening of F508del and I507del mutations was carried out by the multiplex-ARMS-PCR. Significance of differences in mutation frequencies between the patient and control groups was assessed by Fisher's exact test. The DELTA F508 was detected in three patients. However there are no significant association was found between the presence of this mutated allele and infertility [OR=9.2 [allele-based] and 7.2 [individual-based], P=0.179]. None of the samples carried the DELTA I507 mutation. Altogether, we show that neither DELTA I507 nor DELTA F508 is involved in this population of Iranian infertile males with non-obstructive azoospermia

Incidence of Y-chromosome microdeletions in children whose fathers underwent vasectomy reversal or in vitro fertilization with epididymal sperm aspiration: a case-control study / Incidência de microdeleções do cromossomo Y em filhos de pais que passaram por reversão de vasectomia ou fertilização in vitro com aspiração do epidídimo: um estudo caso-controle

ABSTRACT Objective To evaluate the incidence of Y-chromosome microdeletions in individuals born from vasectomized fathers who underwent vasectomy reversal or in vitro fertilization with sperm retrieval by epididymal aspiration (percutaneous epididymal sperm aspiration). Methods A case-control study comprising male children of couples in which the man had been previously vasectomized and chose vasectomy reversal (n=31) or in vitro fertilization with sperm retrieval by percutaneous epididymal sperm aspiration (n=30) to conceive new children, and a Control Group of male children of fertile men who had programmed vasectomies (n=60). Y-chromosome microdeletions research was performed by polymerase chain reaction on fathers and children, evaluating 20 regions of the chromosome. Results The results showed no Y-chromosome microdeletions in any of the studied subjects. The incidence of Y-chromosome microdeletions in individuals born from vasectomized fathers who underwent vasectomy reversal or in vitro fertilization with spermatozoa recovered by percutaneous epididymal sperm aspiration did not differ between the groups, and there was no difference between control subjects born from natural pregnancies or population incidence in fertile men. Conclusion We found no association considering microdeletions in the azoospermia factor region of the Y chromosome and assisted reproduction. We also found no correlation between these Y-chromosome microdeletions and vasectomies, which suggests that the assisted reproduction techniques do not increase the incidence of Y-chromosome microdeletions.

RESUMO Objetivo Avaliar a incidência de microdeleções do cromossomo Y em indivíduos nascidos de pais vasectomizados submetidos à reversão de vasectomia ou fertilização in vitro com recuperação de espermatozoides por aspiração do epidídimo (aspiração percutânea de espermatozoides do epidídimo). Métodos Estudo caso-controle que compreende crianças do sexo masculino de casais em que o homem havia sido previamente vasectomizado e escolheu reversão da vasectomia (n=31) ou fertilização in vitro com recuperação espermática por aspiração percutânea de espermatozoides do epidídimo (n=30) para obtenção de novos filhos, e um Grupo Controle de crianças do sexo masculino de homens férteis com vasectomia programada (n=60). A pesquisa de microdeleções do cromossomo Y foi realizada por reação em cadeia da polimerase nos pais e filhos, avaliando 20 regiões do cromossomo. Resultados O resultado não revelou microdeleções do cromossomo Y em qualquer indivíduo estudado. A incidência de microdeleções do cromossomo Y em indivíduos nascidos de pais vasectomizados que sofreram reversão de vasectomia ou fertilização in vitro com espermatozoides recuperados pela aspiração percutânea de espermatozoides do epidídimo não diferiu entre os grupos, e não houve nenhuma diferença entre indivíduos controle nascidos de gestações naturais ou incidência populacional em homens férteis. Conclusão Não foi encontrada nenhuma associação considerando microdeleções da região do fator de azoospermia no cromossomo Y e reprodução assistida. Não houve correlação entre microdeleções do cromossomo Y e vasectomia, o que sugere que as técnicas de reprodução assistida não aumentam a incidência de microdeleções do cromossomo Y.

45,X/46,XY mosaicism: report on 14 patients from a Brazilian hospital. A retrospective study / Mosaicismo 45,X/46,XY: relato de 14 pacientes de um hospital do Brasil. Um estudo retrospectivo

CONTEXT AND OBJECTIVE: 45,X/46,XY mosaicism, or mixed gonadal dysgenesis, is considered to be a rare disorder of sex development. The aim of our study was to investigate the clinical and cytogenetic characteristics of patients with this mosaicism. DESIGN AND SETTING: A retrospective study in a referral hospital in southern Brazil. METHODS: Our sample consisted of patients diagnosed at the clinical genetics service of a referral hospital in southern Brazil, from 1975 to 2012. Clinical and cytogenetic data were collected from the medical records. RESULTS: Fourteen patients were included in the sample, with ages at the first evaluation ranging from 2 days to 38 years. Nine of them had female sex of rearing and five, male. Regarding the external genitalia, most were ambiguous (n = 10). One patient presented male phenotype and was treated for a history of azoospermia, while three patients presented female phenotype, of whom two had findings of Turner syndrome and one presented secondary amenorrhea alone. Some findings of Turner syndrome were observed even among patients with ambiguous genitalia. None presented gonadal malignancy. One patient underwent surgical correction for genital ambiguity and subsequent exchange of sex of rearing. Regarding cytogenetics, we did not observe any direct correlation between percentages of cell lines and phenotype. CONCLUSIONS: 45,X/46,XY mosaicism can present with a wide variety of phenotypes resulting from the involvement of different aspects of the individual. All these observations have important implications for early recognition of these patients and their appropriate management. .

CONTEXTO E OBJETIVO: O mosaicismo 45,X/46,XY, ou disgenesia gonadal mista, é considerado uma doença rara do desenvolvimento sexual. O objetivo do nosso estudo foi verificar as características clínicas e citogenéticas de pacientes com este mosaicismo. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo em um hospital de referência no sul do Brasil. MÉTODOS: Nossa amostra foi composta por pacientes diagnosticados em um serviço de genética clínica de um hospital de referência no sul do Brasil, no período de 1975 até 2012. Os dados clínicos e citogenéticos foram coletados a partir dos prontuários médicos. RESULTADOS: Catorze pacientes foram incluídos na amostra, idades na primeira avaliação variando de 2 dias a 38 anos. Nove deles apresentavam sexo feminino de criação e cinco, masculino. A genitália externa, na maioria, era ambígua (n = 10). O paciente com fenótipo masculino foi tratado por história de azoospermia, enquanto que das três pacientes do fenótipo feminino, duas apresentavam achados da síndrome de Turner e a outra, amenorreia secundária isolada. Alguns achados da síndrome de Turner foram observados mesmo entre pacientes com genitália ambígua. Nenhum deles apresentou neoplasia gonadal. Um paciente foi submetido à correção cirúrgica de ambiguidade genital e posterior troca de sexo de criação. Quanto à citogenética, não observamos correlação direta entre a porcentagem de linhas de células e o fenótipo. CONCLUSÕES: O mosaicismo 45,X/46,XY pode apresentar grande variedade de fenótipos resultantes do envolvimento de diferentes aspectos do indivíduo. Todas essas observações têm implicações importantes para o reconhecimento precoce desses pacientes e seu adequado manejo. .

No CAG repeat expansion of polymerase gamma is associated with male infertility in Tamil Nadu, South India.

Mitochondria contains a single deoxyribonucleic acid (DNA) polymerase, polymerase gamma (POLG) mapped to long arm of chromosome 15 (15q25), responsible for replication and repair of mitochondrial DNA. Exon 1 of the human POLG contains CAG trinucleotide repeat, which codes for polyglutamate. Ten copies of CAG repeat were found to be uniformly high (0.88) in different ethnic groups and considered as the common allele, whereas the mutant alleles (not -10/not -10 CAG repeats) were found to be associated with oligospermia/oligoasthenospermia in male infertility. Recent data suggested the implication of POLG CAG repeat expansion in infertility, but are debated. The aim of our study was to explore whether the not -10/not -10 variant is associated with spermatogenic failure. As few study on Indian population have been conducted so far to support this view, we investigated the distribution of the POLG CAG repeats in 61 infertile men and 60 normozoospermic control Indian men of Tamil Nadu, from the same ethnic background. This analysis interestingly revealed that the homozygous wild type genotype (10/- 10) was common in infertile men (77% - 47/61) and in normozoospermic control men (71.7% - 43/60). Our study failed to confirm any influence of the POLG gene polymorphism on the efficiency of the spermatogenesis.

Comparative expression analysis of septin 14 in testes of infertile men with normal spermatogenesis and spermatogenic failure

Septins are an evolutionary conserved group of GTP-binding and filament-forming proteins that have diverse cellular roles. An increasing body of data implicates the septin family in the pathogenesis of diverse states including cancers, neurodegeneration, and male infertility. The objective of the study was to evaluate the expression pattern of Septin14 in testis tissue of men with and without spermatogenic failure. The samples retrieved accessible random between infertile men who underwent diagnostic testicular biopsy in Royan institute. 10 infertile men with obstructive azoospermia and normal spermatogenesis and 20 infertile men with non-obstructive azoospermia were recruited for real-time reverse transcription [RT]-PCR analysis of the testicular tissue. Total RNA was extracted with trizol reagent. Comparison of the mRNA level of septin14 revealed that in tissues with partial [n=10] or complete spermatogenesis [n=10], the expression of septin 14 was significantly higher than sertoli cell only tissues. The testicular tissues of men with hypospermatogenesis, maturation arrest and sertoli cell only had lower levels of septin 14 transcripts than normal men. These data indicates that Septin 14 expression level is critical for human spermatogenesis

Update in the evaluation of the azoospermic male

Approximately 1% of all men in the general population suffer from azoospermia, and azoospermic men constitute approximately 10 to 15% of all infertile men. Thus, this group of patients represents a significant population in the field of male infertility. A thorough medical history, physical examination and hormonal profile are essential in the evaluation of azoospermic males. Imaging studies, a genetic workup and a testicular biopsy (with cryopreservation) may augment the workup and evaluation. Men with nonobstructive azoospermia should be offered genetic counseling before their spermatozoa are used for assisted reproductive techniques. This article provides a contemporary review of the evaluation of the azoospermic male.

A comprehensive review of genetics and genetic testing in azoospermia

Azoospermia due to obstructive and non-obstructive mechanisms is a common manifestation of male infertility accounting for 10-15% of such cases. Known genetic factors are responsible for approximately 1/3 of cases of azoospermia. Nonetheless, at least 40% of cases are currently categorized as idiopathic and may be linked to unknown genetic abnormalities. It is recommended that various genetic screening tests are performed in azoospermic men, given that their results may play vital role in not only identifying the etiology but also in preventing the iatrogenic transmission of genetic defects to offspring via advanced assisted conception techniques. In the present review, we examine the current genetic information associated with azoospermia based on results from search engines, such as PUBMED, OVID, SCIENCE DIRECT and SCOPUS. We also present a critical appraisal of use of genetic testing in this subset of infertile patients.