Association of spermatogenic failure with the b2/b3 partial AZFc deletion.
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ABSTRACT:
SUBMITTER: Eloualid A
PROVIDER: S-EPMC3325924 | biostudies-other | 2012
REPOSITORIES: biostudies-other
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Project description:To determine the involvement of Copy Number Variants (CNVs) in the origin of male infertility, patients with idiopathic severe oligozoospermia, Sertoli-cell-only syndrome and controls with normozoospermia were analysed by array CGH using the 244A/400K array sets (Agilent Technologies). Comparison of 89 infertile male patients with severe oligozoospermia (≤5 x Mill./ml sperm concentration and ≤10 Mill. total sperm count) and 37 with azoospermia due to complete, bilateral Sertoli-cell-only syndrome (SCOS) with 100 healthy controls with normal semen parameters (≥20 Mill./ml sperm concentration, ≥40 Mill. total sperm count, ≥2 ml semen volume, ≥50% of a+b or ≥25% a motility, high percentage of normal forms (≥10%)). Patients with recurring, patient-specific and mostly private, sex-chromosomal CNVs (29 with OAT and 17 with SCOS) are reported as possibly causing spermatogenic failure.
2011-03-17 | E-GEOD-27965 | biostudies-arrayexpress
Project description:To determine the involvement of Copy Number Variants (CNVs) in the origin of male infertility, patients with idiopathic severe oligozoospermia, Sertoli-cell-only syndrome and controls with normozoospermia were analysed by array CGH using the 244A/400K array sets (Agilent Technologies).
2011-03-17 | GSE27965 | GEO
Project description:Approximately 10%-15% of couples are infertile, and a male factor is involved in almost half of these cases. This observation is due in part to defects in spermatogenesis, and the underlying causes, including genetic abnormalities, remain largely unknown. Until recently, the only genetic tests used in the diagnosis of male infertility were aimed at detecting the presence of microdeletions of the long arm of the Y chromosome and/or chromosomal abnormalities. Various other single-gene or polygenic defects have been proposed to be involved in male fertility. However, their causative effects often remain unproven. The recent evolution in the development of whole-genome-based techniques and the large-scale analysis of mouse models might help in this process. Through knockout mouse models, at least 388 genes have been shown to be associated with spermatogenesis in mice. However, problems often arise when translating this information from mice to humans.
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Project description:Piwi-interacting RNAs (piRNAs) are a broad group of noncoding small RNAs that have important biological functions in germline cells and can maintain genome integrity via silencing of retrotransposons. In this study, we aimed to explore the associations between genetic variants of important genes involved in piRNA biogenesis and male infertility with spermatogenic impairment.To this end, five single-nucleotide polymorphisms (SNPs) in the ASZ1, PIWIL1, TDRD1, and TDRD9 genes were genotyped by TaqMan allelic discrimination assays in 342 cases of nonobstructive azoospermia (NOA) and 493 controls.The SNP rs77559927 in TDRD1 was associated with a reduced risk of spermatogenic impairment. The genotypes TC and TC?+?CC showed odds ratios and 95 % confidence intervals of 0.73 (0.55-0.98, P?=?0.034) and 0.73 (0.56-0.97, P?=?0.030), respectively, in patients with NOA compared with those in the controls.Thus, our results provided the first epidemiological evidence supporting the involvement of TDRD1 genetic polymorphisms in piRNA processing genes in determining the risk of spermatogenic impairment in a Han Chinese population.
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Project description:Coenurus cerebralis, the metacestode of Taenia multiceps, causes coenurosis, a disease severely affecting goat, sheep, cattle and yak farming and resulting in huge economic losses annually. Annexins bind calcium ions and play an important role in flatworm parasite development. To explore potential functions of annexins in T. multiceps, three homologous genes, namely, TmAnxB2, TmAnxB3 and TmAnxB12, were screened from the transcriptome dataset, amplified from C. cerebralis cDNA and subjected to bioinformatics analysis. Then, polyclonal antibodies recognizing the recombinant TmAnxB2 (rTmAnxB2) and rTmAnxB3 were prepared for localization of TmAnxB2 and TmAnxB3 in different tissues and developmental stages by immunofluorescence. The transcription of all three genes was also measured by relative fluorescent quantitative PCR. The sizes of rTmAnxB2, rTmAnxB3 and rTmAnxB12 were 58.00, 53.06 and 53.51 kDa, respectively, and rTmAnxB12 was unstable. Both rTmAnxB2 and rTmAnxB3 were recognized by goat-positive T. multiceps sera in Western blots. Immunofluorescence revealed that TmAnxB2 and TmAnxB3 were localized in the protoscolex and cyst wall and TmAnxB3 was also detected in adult cortex. TmAnxB2 and TmAnxB12 mRNA levels were determined to be highest in oncospheres and protoscolex, whereas transcription of TmAnxB3 was highest in scolex and immature segments. Taken together, these findings indicate that TmAnxB2 and TmAnxB12 may play critical roles in T. multiceps larvae, while TmAnxB3 may have important functions in adults. These results will lay the foundation for functional research of annexins in T. multiceps.
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Project description:Non-obstructive azoospermia (NOA) is the most severe form of male infertility and typically incurable. Defining the genetic basis of NOA has proven challenging, and the most advanced classification of NOA subforms is not based on genetics, but simple description of testis histology. In this study, we exome-sequenced over 1000 clinically diagnosed NOA cases and identified a plausible recessive Mendelian cause in 20%. We find further support for 21 genes in a 2-stage burden test with 2072 cases and 11,587 fertile controls. The disrupted genes are primarily on the autosomes, enriched for undescribed human "knockouts", and, for the most part, have yet to be linked to a Mendelian trait. Integration with single-cell RNA sequencing data shows that azoospermia genes can be grouped into molecular subforms with synchronized expression patterns, and analogs of these subforms exist in mice. This analysis framework identifies groups of genes with known roles in spermatogenesis but also reveals unrecognized subforms, such as a set of genes expressed across mitotic divisions of differentiating spermatogonia. Our findings highlight NOA as an understudied Mendelian disorder and provide a conceptual structure for organizing the complex genetics of male infertility, which may provide a rational basis for disease classification.
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Project description:ImportanceStudies on uveal melanomas (UMs) have demonstrated the prognostic value of 8q gain and monosomy 3, but the prognosis of UMs with partial deletion of chromosome 3 remains to be defined.ObjectiveTo examine the association of partial chromosome 3 deletion in UMs with metastasis-free survival.Design, setting, and participantsThis retrospective cohort study of 1088 consecutive comparative genomic hybridization arrays performed from May 1, 2006, to July 31, 2015, assessed patients presenting with UMs with and without partial loss of chromosome 3 at a referral center. Data analysis was performed from September 1, 2017, to November 30, 2017.ExposureUveal melanoma with or without partial loss of chromosome 3.Main outcomes and measuresMetastasis-free survival and overall survival at 60 months.ResultsOf the 1088 consecutive comparative genomic hybridization arrays that were performed, 43 UMs (4.0%) in 43 patients (median age, 58 years [range, 12-79 years]; 22 [51%] female) carried partial deletions of chromosome 3. Median follow-up was 66 months (range, 1.2-126.2 months). Metastasis-free survival at 60 months was 33.6% (95% CI, 15.8%-71.4%) for UMs that carried a deletion of the BAP1 (BRCA1 associated protein 1) locus (BAP1del; 24 tumors) and 80.5% (95% CI, 64.8%-100%) for UMs without the loss of the BAP1 locus (BAP1 normal [BAP1nl]; 19 tumors) (log-rank P = .001). Overall survival at 60 months was 64.5% (95% CI, 43.5%-95.8%) in the BAP1del group vs 84.1% (95% CI, 69.0%-100%) in the BAP1nl group (log-rank P < .001). In these 43 cases, metastasis-free survival at 60 months was 100% for UMs without loss of the BAP1 locus or 8q gain, 70.0% (95% CI, 50.5%-96.9%) for UMs that carried 1 of these alterations, and 12.5% (95% CI, 2.1%-73.7%) for those that carried both (log-rank P < .001). Similarly, overall survival at 60 months was 100% for UMs without loss of the BAP1 locus or 8q gain, 80.8% (95% CI, 63.3%-100%) for UMs that carried 1 of these alterations, and 46.7% (95% CI, 23.3%-93.6%) for those that carried both (log-rank P < .001).Conclusions and relevanceThese findings suggest that partial deletion of chromosome 3 encompassing the BAP1 locus is associated with poor prognosis. A cytogenetic classification of UMs could be proposed based on the status of the BAP1 locus instead of the chromosome 3 locus, while also taking chromosome 8q into account.
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Project description:IntroductionHip arthroplasty (HA) is commonly performed to treat various hip pathologies. Its volume is expected to rise further due to the increasing age of the population. Complication rates are low; however, periprosthetic femoral fractures (PFF) are a rare, albeit serious, complication with substantial economic impact. While current guidelines propose revision with long-stemmed prostheses for all Vancouver B2 and B3 PFF, some recent research papers suggest that open reduction with internal fixation (ORIF) could lead to an equivalent outcome. Our aim was to summarize the evidence, elucidating under which circumstances ORIF leads to a favorable outcome after B2 and B3 PFF compared with revision surgery.Materials and methodsA systematic literature search was performed to identify studies on patients treated with ORIF and with stem revision after B2 and/or B3 fractures. Extracted information included initial pathology, stem fixation mechanism, bone quality and stem stability at the time of PFF, clinical outcomes, and mortality. Results of individual studies were summarized in a table in lieu of a quantitative data synthesis due to a lack of standardized information.ResultsWe identified 14 original research articles including both patients treated with ORIF and with stem revision after B2 and/or B3 PFF. Five studies included statistical comparisons, all were in favor of ORIF or indeterminate. The common lack of rigorous statistical analyses and significant methodological weaknesses made identification of outcome predictors impossible.ConclusionThe choice of treatment modality for PFF depends on fracture, implant, and bone characteristics. Recent data show that successful outcome can be achieved without revising loose stems. ORIF may be a viable option if bone stock is adequate around uncemented or tapered polished stems with an intact cement mantle and the fracture geometry allows stable anatomic reconstruction. Conceptional considerations support this idea, but more data are needed to identify outcome predictors.
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