In the article we present a case report of a young man who was undergoing investigation for infertility. Spermogram results showed azoospermia. Only a complex sexological, urological and genetic examination found the cause of the couple's infertility, namely a structural aberration of the Y chromosome - isochromosome i(Y)(p10), duplication of the short arm of the Y chromosome and deletion of the entire long arm of the Y chromosome (hence the entire AZF gene region). This finding correlated with the clinical findings of azoospermia. Isochromosome Yp (ORPHA:98797) is a rare gonosomal aberration characterised by variable clinical manifestations including: normal healthy fertile men, men with infertility and men with ambiguous genitalia and incomplete masculinisation. After the discovery of this chromosomal aberration, the couple decided to undergo assisted reproduction using donor sperm.
Male infertility is a global public health concern. Teratozoospermia is a qualitative anomaly of spermatozoa morphology, contributing significantly to male infertility, whereas azoospermia is the complete absence of spermatozoa in the ejaculate. Thus, there is a serious need for unveiling the common origin and/or connection between both of these diseases, if any. This study aims to identify common potential biomarker genes of these two diseases via an in silico approach using a meta-analysis of microarray data. In this study, a differential expression analysis of genes was performed on four publicly available RNA microarray datasets, two each from teratozoospermia (GSE6872 and GSE6967) and azoospermia (GSE145467 and GSE25518). From the analysis, 118 DEGs were found to be common to teratozoospermia and azoospermia, and, interestingly, sperm autoantigenic protein 17 (SPA17) was found to possess the highest fold change value among all the DEGs (9.471), while coiled-coil domain-containing 90B (CCDC90B) and coiled-coil domain-containing 91 (CCDC91) genes were found to be common among three of analyses, i.e., Network Analyst, ExAtlas, and GEO2R. This observation indicates that SPA17, CCDC90B, and CCDC91 genes might have significant roles to play as potential biomarkers for teratozoospermia and azoospermia. Thus, our study opens a new window of research in this area and can provide an important theoretical basis for the diagnosis and treatment of both these diseases.
Male infertility is a serious problem in an increasing number of couples. We report an infertile man with non-obstructive azoospermia and karyotype 45,XY,rob(14;22). The immunofluorescence analysis of his testicular tissue using antibodies to SYCP1, SYCP3, HORMAD2, MLH1, and centromeres showed delayed synapsis of the chromosomes involved in the translocation, a varying extent of trivalent asynapsis and its association with sex chromosomes. The mean frequency of meiotic recombination per cell was within the range of normal values. Fluorescence in situ hybridization (FISH) with probes for chromosomes 14 and 22 revealed 5.83% of chromosomally abnormal testicular spermatozoa. FISH with probes for chromosomes X, Y, and 21 showed frequencies of disomic and diploid testicular spermatozoa increased when compared to ejaculated sperm of healthy donors, but comparable with published results for azoospermic patients. PGD by FISH for the translocation and aneuploidy of chromosomes X, Y, 13, 18, and 21 showed a normal chromosomal complement in one out of three analyzed embryos. A healthy carrier girl was born after the embryo transfer. This study shows the benefits of preimplantation genetic diagnosis in a case of a rare Robertsonian translocation carrier with azoospermia and a relatively low frequency of chromosomally unbalanced testicular spermatozoa.
- MeSH
- aneuploidie * MeSH
- azoospermie genetika MeSH
- detekce genetických nosičů * MeSH
- karyotypizace MeSH
- lidé MeSH
- lidské chromozomy, pár 14 * MeSH
- lidské chromozomy, pár 22 * MeSH
- meióza genetika MeSH
- spermie metabolismus MeSH
- translokace genetická * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
BACKGROUND: High-throughput studies provide a wide spectrum of genes for use as predictive markers during testicular sperm extraction (TESE) in combination with ICSI. In this work, we used the specimens from testicular biopsies of men with non-obstructive azoospermia who underwent TESE to investigate the expression of spermatogenesis-related genes MND1, SPATA22, GAPDHS and ACR. METHODS: Testicular biopsy specimens were subdivided into three groups: hypospermatogenesis (HS); maturation arrest (MA); and Sertoli cell-only syndrome (SCO). The levels of expression of the spermatogenesis-related genes MND1, SPATA22, GAPDHS and ACR in the testes were compared among these three groups using the reverse transcription polymerase chain reaction (RT-PCR) technique. RESULTS: Analysis of the expression of spermatogenic genes in human testes with abnormal spermatogenesis showed different expression patterns in patients from different groups. Fertilization rate for studied set of patients was 66% and pregnancy rate 29%. For HS group fertilization rate was 72% and pregnancy rate 32%, while for MA group fertilization and pregnancy rates were 54% and 26%, respectively. Fertilization rates in relation to the studied genes were uniformly around 70%, pregnancy rates for ACR and GAPDHS genes were surprisingly low at 6% and 8% correspondingly. CONCLUSIONS: Analysis of the expression of genes involved in spermatogenesis can be a fast additional test for the level of spermatogenesis in testicular samples.
- MeSH
- akrosin genetika MeSH
- azoospermie genetika patologie MeSH
- biopsie MeSH
- dospělí MeSH
- fertilizace MeSH
- glyceraldehyd-3-fosfátdehydrogenasy genetika MeSH
- intracytoplazmatické injekce spermie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci varlat genetika patologie MeSH
- odběr spermií MeSH
- oligospermie genetika patologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- proteiny buněčného cyklu genetika MeSH
- Sertoli cell only syndrom genetika patologie MeSH
- spermatogeneze genetika MeSH
- stanovení celkové genové exprese MeSH
- těhotenství MeSH
- testis metabolismus patologie MeSH
- úhrn těhotenství na počet žen v reprodukčním věku MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- azoospermie genetika MeSH
- chromozomální aberace MeSH
- chromozomální delece MeSH
- cystická fibróza genetika MeSH
- delece genu MeSH
- ductus deferens abnormality embryologie MeSH
- fenotyp MeSH
- genetické nemoci vrozené * genetika MeSH
- genetické poradenství MeSH
- intracytoplazmatické injekce spermie MeSH
- karyotyp MeSH
- Klinefelterův syndrom genetika patofyziologie MeSH
- lidé MeSH
- lidský chromozom Y MeSH
- mutace MeSH
- mužská infertilita * genetika MeSH
- oligospermie genetika MeSH
- protein CFTR genetika MeSH
- spermatogeneze genetika MeSH
- spermie cytologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- směrnice pro lékařskou praxi MeSH
BACKGROUND: Non-obstructive azoospermic (NOA) men can father children after testicular sperm extraction (TESE). Previous studies suggest that they may be at risk of producing chromosomally abnormal spermatozoa, but the number of sperm analysed per patient was usually very low. METHODS: Multicolour fluorescence in situ hybridization was used for detection of chromosome 13, 15, 16, 18, 21, 22, X and Y disomy and diploidy in sperm obtained from NOA men (n = 17) and control donors (n = 10). At least 500 testicular sperm were scored in each patient to increase the precision of our study. RESULTS: The mean frequency of overall disomy (2.32%) and diploidy (0.80%) found in 13 689 testicular spermatozoa of NOA patients was significantly higher than in the ejaculated sperm of normospermic control donors, disomy (0.62%) and diploidy (0.29%). A highly significant increase in frequencies of chromosome 15, Y and overall disomy (P < 0.001), and a significant increase in disomy of chromosome 13 (P = 0.002), 16 (P = 0.031) and 21 (P = 0.018), overall diploidy (P = 0.031) and diploidy caused by errors in meiosis I (P = 0.011) were observed in the NOA group. CONCLUSIONS: Testicular sperm samples of NOA patients show a higher incidence of numerical chromosomal abnormalities compared with ejaculated sperm of control donors. Appropriate genetic counselling is necessary in NOA men undergoing TESE.
- MeSH
- aneuploidie MeSH
- azoospermie genetika MeSH
- chromozomální aberace MeSH
- dospělí MeSH
- hybridizace in situ fluorescenční MeSH
- lidé středního věku MeSH
- lidé MeSH
- mapování chromozomů MeSH
- meióza MeSH
- přenos embrya MeSH
- riziko MeSH
- senioři MeSH
- spermie patologie MeSH
- testis patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Aims. The Y chromosome accumulates male-related genes including sex-determining region of Y-chromosome (SRY) and several spermatogenesis-related genes. The long arm contains azoospermia factor (AZF) region (including sub-regions AZFa, AZFb and AZFc). Microdeletions in this region are responsible for azoospermia and oligospermia and result in the male infertility. The aim of this study was to analyze incidence of microdeletions in the AZF region of Y chromosome in patients with azoospermia from Slovakia. Patients and Methods. Over the period from 2005 to 2009 a total of 239 men (mean age 31.74 years) were analyzed. The diagnosis of azoospermia was established on the basis of semen analysis. All patient samples were analyzed cytogenetically. Chromosomal analysis was performed on all patients on cultured lymphocytes from peripheral blood. For exact diagnosis of microdeletions in AZF region we used a PCR-method using a set of sequence-tagged sites from all AZF sub-regions (according to the recommendation by the European Academy of Andrology and the European Quality Monitoring Network Group). Results. Among our 226 patients with azoospermia and with normal karyotype, 8 patients (mean age 30.6 years) had microdeletions in the AZF region of the Y chromosome (3.35%). Considering particular types of deletions we determined deletions in each region AZFa,b,c but also a complete deletion of the entire AZF region. The presence of microdeletion(s) in the AZFc region was the most frequent. In our study we found 12 patients (5%) with 47,XXY karyotype (Klinefelter syndrome), but these patients didn't have microdeletion of Y chromosomes. Conclusion. The study confirmed that percentage of microdeletions in the AZF region is low in Slovak azoospermic patients, but important from a prognostic view.
- MeSH
- azoospermie genetika MeSH
- chromozomální delece MeSH
- dospělí MeSH
- lidé MeSH
- lidský chromozom Y genetika MeSH
- proteiny semenné plazmy genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Geografické názvy
- Slovenská republika MeSH
Cieľ štúdie: Zavedenie metódy DNA analýzy AZF (Azoospermia factor region) oblasti Y chromozómu u mužov s poruchami plodnosti v Slovenskej republike. Typ štúdie: Genetická-prospektívna štúdia. Názov a sídlo pracoviska: Ústav lekárskej biológie, genetiky a klinickej genetiky LFUK a FNsP, Bratislava. Metodika: Detekcia bola robená pomocou polymerázovej reťazovej reakcie, použitím troch rôznych sád sY sekvencií. Na overenie niektorých typov delécií bol použitý fluorescenčne značený diagnostický set. Výsledky: Súbor tvorilo 822 mužov, z nich 349 s azoospermiou a 473 s oligospermiou. Delécie v AZF oblasti Y chromozómu boli potvrdené v 38 prípadoch (4,62 %). Z nich je 24 (6,88 %) pacientov zo súboru s azoospermiou a 14 zo súboru pacientov s oligospermiou (2,95 %). Zaznamenali sme delécie v každej z podoblastí AZF (a, b, c), kombinovanú AZFbc deléciu, ale aj deléciu celej AZF oblasti. Záver: Štúdia potvrdila, že detekcia mikrodelécii AZF oblasti má diagnostický a prognostický význam a poukázala na dôležitosť selekčných kritérií výberu pacientov.
Objective: Study on Y chromosomal AZF region deletions in Slovak population, application of DNA technique. Design: Genetic-prospective study. Setting: Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava. Methods: For detecting microdeletions in the Y-chromosomal AZF region in men with fertility disorders and for identifying Y-specific sequences we used the method of polymerase chain reaction (PCR) with using three different sets of sY sequences. For a verification of the specific type of deletion we used also fluorescently labeled kit. Results: Diagnoses of referred patients were divided into 2 groups: azoospermia, oligospermia. In the followed-up group of 822 patients there were 349 patients with azoospermia, 473 patients with oligospermia. Globally we reported 38 cases of deletions in the AZF region of the Y chromosome, i.e. 4.62%. 24 patients with deletion are from the group of patients with azoospermia, i.e. 6.88%, 14 patients are from the group of patients with oligospermia (2.95%). Considering particular types of deletions we recorded deletions in each region, AZFa, AZFb and AZFc, combinated AZFbc deletion, but also a complete deletion of the whole AZF region. Conclusion: The study confirmed that detection of microdeletions of the AZF region is significant from diagnostic and prognostic view and it pointed out the importance of selection criteria for selecting patients.
- MeSH
- azoospermie genetika MeSH
- chromozomální delece MeSH
- dospělí MeSH
- lidé genetika MeSH
- lidský chromozom Y genetika MeSH
- mužská infertilita genetika MeSH
- oligospermie genetika MeSH
- polymerázová řetězová reakce MeSH
- proteiny semenné plazmy genetika MeSH
- sekvenční analýza DNA MeSH
- Check Tag
- dospělí MeSH
- lidé genetika MeSH
- mužské pohlaví MeSH
