Proteomic biomarkers in seminal plasma as predictors of reproductive potential in azoospermic men
Ontology highlight
ABSTRACT:
INSTRUMENT(S):
ORGANISM(S): Homo Sapiens (human)
DISEASE(S): Male Infertility
SUBMITTER: 
Laura Dagley
LAB HEAD: Daniela Fietz
PROVIDER: PXD045519 | Pride | 2024-03-20
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| P3790_A10_Slot1-15_1_3613.d.zip | Other | |||
| P3790_A11_Slot1-22_1_3659.d.zip | Other | |||
| P3790_A12_Slot1-21_1_3619.d.zip | Other | |||
| P3790_A1_Slot1-37_1_3635.d.zip | Other | |||
| P3790_A2_Slot1-20_1_3618.d.zip | Other |
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Project description:Male factor infertility is involved in almost half of all infertile couples. Lack of the ejaculated sperm owing to testicular malfunction has been reported in 6-10% of infertile men, a condition named nonobstructive azoospermia (NOA). In this study, we investigated untargeted metabolomic profiling of the seminal plasma in NOA men using gas chromatography-mass spectrometry and advance chemometrics. In this regard, the seminal plasma fluids of 11 NOA men with TESE-negative, nine NOA men with TESE-positive and 10 fertile healthy men (as a control group) were collected. Quadratic discriminate analysis (QDA) technique was implemented on total ion chromatograms (TICs) for identification of discriminatory retention times. We developed multivariate classification models using the QDA technique. Our results revealed that the developed QDA models could predict the classes of samples using their TIC data. The receiver operating characteristic curves for these models were >0.88. After recognition of discriminatory retention time's asymmetric penalized least square, evolving factor analysis, correlation optimized warping and alternating least squares strategies were applied for preprocessing and deconvolution of the overlapped chromatographic peaks. We could identify 36 discriminatory metabolites. These metabolites may be considered discriminatory biomarkers for different groups in NOA.
2018-04-19 | MTBLS420 | MetaboLights
Project description:Infertility affects about one in six couples attempting pregnancy, with the man responsible in approximately half of the cases. Because the pathophysiology underlying azoospermia is not elucidated, most male infertility is diagnosed as idiopathic. Genome-wide gene expression analyses with microarray on testis specimens from 47 non-obstructive azoospermia (NOA) and 11 obstructive azoospermia (OA) patients were performed, and 2,611 transcripts that preferentially included genes relevant to gametogenesis and reproduction according to Gene Ontology classification were found to be differentially expressed. Using a set of 945 of the 2,611 transcripts without missing data, NOA was further categorized into three classes using the non-negative matrix factorization method. These three subclasses showed differences in Johnsenâs score, FSH level, and LH level. In addition, the 52 genes showing high statistical difference between NOA subclasses (P < 0.01 with Tukey's post hoc test) were subjected to allelic association analyses to identify genetic susceptibilities in 442 NOA patients and 475 fertile men. After two rounds of screening, SNPs of the ADP-ribosyltransferase 3 (ART3) gene were associated with NOA with highest significance with ART3-SNP25 (rs6836703; P = 0.0025). Haplotypes with 5 SNPs were constructed, and the most common haplotype was found to be under-represented in patients (NOA 26.6 % versus control 35.3 %, P = 0.000073). Subjects having the most common haplotype showed an elevated level of testosterone, suggesting a protective effect of the haplotype on spermatogenesis. Thus, genome-wide gene expression analyses were used to identify genes involved in the pathogenesis of NOA, and ART3 was subsequently identified as a susceptibility gene for NOA. These findings clarify the molecular pathophysiology of NOA and suggest a novel therapeutic target in the treatment of NOA. Experiment Overall Design: Comparative analysis of two disease phenotypes, using testicular biopsy specimens from 47 NOA and 11 OA patients. No experimental replicates.
2008-06-16 | E-GEOD-9210 | biostudies-arrayexpress
Project description:About half of testicular sperm extraction (TESE) procedures in men with non-obstructive azoospermia (NOA), including men with Klinefelter syndrome (KS), are unsuccessful. To avoid unnecessary invasive surgery, biomarkers for spermatozoa have been studied and identified. In addition, markers for spermatogonia in testis tissue have been researched. This study aimed to find biomarkers in semen and/or urine of NOA patients to predict the presence of spermatogonia in the testis. This would especially be interesting for young boys. Differentially expressed miRNAs were identified (1) between samples from patients with and those of patients without a positive TESE procedure as well as (2) between TESE negative patients with and those without spermatogonia. A total of ten up-regulated miRNAs (seven in seminal plasma and three in urine) were found in the TESE-negative/spermatogonia-positive group compared to the TESE-negative/spermatogonia-negative group. These miRNAs could become biomarkers for spermatogonia, however, more research is necessary.
2023-02-06 | GSE224511 | GEO
Project description:This project presents an in-depth site-specific N-glycoproteomic analysis of extracellular vesicles (EVs) isolated from human seminal plasma, aiming to identify diagnostic biomarkers for the molecular typing of azoospermia. Using an optimized EVGlyco platform, we characterized 8,435 site-specific N-glycans from 394 N-glycoproteins in EVs, with targeted validation via parallel reaction monitoring (PRM) confirming key glycan signatures (e.g., MPO-N355-H6N2, ACP3-N94-H5N4F1, and CLU-N374-H10N9F1) that distinguish obstructive azoospermia (OA) from nonobstructive azoospermia (NOA) and its subtypes (hypospermatogenesis, maturation arrest, Sertoli cell-only syndrome). The dataset includes mass spectrometry raw files of intact N-glycopeptides from 110 seminal plasma samples (discovery and validation cohorts), supporting the potential of EV site-specific N-glycans as non-invasive biomarkers for azoospermia typing.
2026-08-17 | PXD080611 | Pride
Project description:This project presents an in-depth site-specific N-glycoproteomic analysis of extracellular vesicles (EVs) isolated from human seminal plasma, aiming to identify diagnostic biomarkers for the molecular typing of azoospermia. Using an optimized EVGlyco platform, we characterized 8,435 site-specific N-glycans from 394 N-glycoproteins in EVs, with targeted validation via parallel reaction monitoring (PRM) confirming key glycan signatures (e.g., MPO-N355-H6N2, ACP3-N94-H5N4F1, and CLU-N374-H10N9F1) that distinguish obstructive azoospermia (OA) from nonobstructive azoospermia (NOA) and its subtypes (hypospermatogenesis, maturation arrest, Sertoli cell-only syndrome). The dataset includes mass spectrometry raw files of intact N-glycopeptides from 110 seminal plasma samples (discovery and validation cohorts), supporting the potential of EV site-specific N-glycans as non-invasive biomarkers for azoospermia typing.
2026-08-15 | PXD066843 | Pride
Project description:The accurate diagnosis of non-obstructive azoospermia (NOA) and obstructive azoospermia (OA) is crucial for selecting appropriate clinical treatments. This study aimed to investigate the pivotal role of miRNAs in circulating plasma exosomes in distinguishing between NOA and OA, as well as uncovering the signaling pathways involved in azoospermia pathogenesis. In this study, differential expression of extracellular vesicles (EVs) miR-513c-5p and miR-202-5p was observed between NOA and OA patients, while the selenocompound metabolism pathway was identified as relevant to azoospermia pathogenesis through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The predictive power of these microRNAs was evaluated using ROC-AUC analysis, demonstrating promising sensitivity, specificity, and area under the curve values. A binomial regression equation incorporating circulating plasma levels of EVs miR-202-5p and miR-513c-5p along with follicle-stimulating hormone was calculated to provide a clinically applicable method for diagnosing NOA and OA. This study presents a non-invasive testing approach for distinguishing between NOA and OA, offering a valuable tool for clinical practice.
2025-06-18 | GSE270320 | GEO
Project description:Background Non-obstructive azoospermia (NOA) is a leading cause of male infertility, affecting approximately 1% of men worldwide. Accurate pathological diagnosis and subclassification of NOA remain challenging due to the lack of reliable markers for germ cells (GCs) and Sertoli cells (SCs) within seminiferous tubules. Current histopathological evaluation relies on Hematoxylin and Eosin (H/E) staining, which lacks molecular specificity and cannot precisely quantify GCs or identify the stage of spermatogenic arrest. This limits both prognostic accuracy and the development of targeted therapeutic strategies. The identification of robust cellular and molecular markers is therefore essential to improve diagnosis, subclassification, and clinical management of NOA. Methods We performed immunofluorescence staining for SOX9, DAZL, and SYCP3 on 146 testicular samples to refine NOA subtyping. Single-cell RNA sequencing (scRNA-seq) was conducted on samples from 5 NOA patients, integrated with data from healthy and obstructive azoospermia (OA) controls. Candidate markers identified from SC-specific transcriptional profiles were validated via immunofluorescence in human and mouse testicular tissues. Findings Immunostaining enabled a refined classification of NOA into three subtypes: Maturation Arrest-Meiotic Arrested (MA-MA), Maturation Arrest-Premeiotic Arrested (MA-PA), and Sertoli cell-only (SCO). The scRNA-seq revealed that SCs in adult NOA patients exhibit an immature transcriptional state resembling prepubertal SCs, characterized by a distinct metabolic profile. From this profile, we identified LDHB and PKM2 as significantly upregulated markers in NOA SCs. Immunofluorescence confirmed their elevated expression in human NOA samples and in immature mouse testes. Interpretation Our integrated approach establishes a novel immunostaining-based classification for NOA and identifies an immature SC state as a key pathological feature. The overexpression of LDHB and PKM2 in SCs provides two new candidate biomarkers for improving the pathological diagnosis and subclassification of NOA, with potential implications for future diagnostic and therapeutic strategies.
2026-04-03 | GSE326372 | GEO
Project description:Context. Non-obstructive azoospermia (NOA) is the most severe form of male infertility affecting 1% of all men, with a clinical picture characterized by no sperm production, hyalinization of the basal membrane of the seminiferous tubules, primary hypogonadism and earlier onset of age-related comorbidities compared with fertile men. NOA is also characterized by etiologic heterogeneity and the non-genetic form has higher incidence of testicular germ cell cancer (TGCC) compared to the forms with genetic abnormalities. Objective. We aimed to establish molecular pathways in the testicular somatic cells that are either shared or specific for non-genetic and genetic forms of NOA, as Complete Androgen Insensitivity Syndrome (CAIS) and Klinefelter Syndrome (KS). Methods. Single cell RNAseq of the testis somatic cells of an individual with CAIS, and data integration with published scRNA-seq datasets of testis with normal spermatogenesis, NOA, KS and germinal testicular cancer. Detailed clinical data of the CAIS patient, Testosterone and Estradiol levels in age-matched men (120 fertile, 155 infertile, 116 NOA, 18 KS, and 343 with TGCC). Results. In all conditions, Leydig cells are immature and senescent, but those of NOA associated with primary hypogonadism depict the highest expression of transcripts associated with the seminoma microenvironment, including estrogen-responsive genes. An oncological transcriptional signature in the Leydig cells has been confirmed at the systemic levels by showing a prognostic role of the decreasing Testosterone/Estradiol ratio for TGCC in men with non-genetic NOA. Conclusion. This study offers molecular insights into the prediction of TGCC in persons with NOA and eligibility for the use of aromatase inhibitors.
2025-07-21 | GSE298368 | GEO
Project description:Infertility affects about one in six couples attempting pregnancy, with the man responsible in approximately half of the cases. Because the pathophysiology underlying azoospermia is not elucidated, most male infertility is diagnosed as idiopathic. Genome-wide gene expression analyses with microarray on testis specimens from 47 non-obstructive azoospermia (NOA) and 11 obstructive azoospermia (OA) patients were performed, and 2,611 transcripts that preferentially included genes relevant to gametogenesis and reproduction according to Gene Ontology classification were found to be differentially expressed. Using a set of 945 of the 2,611 transcripts without missing data, NOA was further categorized into three classes using the non-negative matrix factorization method. These three subclasses showed differences in Johnsen’s score, FSH level, and LH level. In addition, the 52 genes showing high statistical difference between NOA subclasses (P < 0.01 with Tukey's post hoc test) were subjected to allelic association analyses to identify genetic susceptibilities in 442 NOA patients and 475 fertile men. After two rounds of screening, SNPs of the ADP-ribosyltransferase 3 (ART3) gene were associated with NOA with highest significance with ART3-SNP25 (rs6836703; P = 0.0025). Haplotypes with 5 SNPs were constructed, and the most common haplotype was found to be under-represented in patients (NOA 26.6 % versus control 35.3 %, P = 0.000073). Subjects having the most common haplotype showed an elevated level of testosterone, suggesting a protective effect of the haplotype on spermatogenesis. Thus, genome-wide gene expression analyses were used to identify genes involved in the pathogenesis of NOA, and ART3 was subsequently identified as a susceptibility gene for NOA. These findings clarify the molecular pathophysiology of NOA and suggest a novel therapeutic target in the treatment of NOA. Keywords: Disease state analysis
2007-12-31 | GSE9210 | GEO
Project description:The objective of this study was to determine whether prostate cancer-associated miRNAs are present in seminal fluid and, if so, evaluate their diagnostic potential. Small RNA sequencing was used to profile and compare miRNAs in the non-sperm cellular fraction of seminal fluid from men with biopsy-proven cancer (one pooled sample from 6 men) and men with elevated serum PSA but negative biopsy results (one pooled sample from 6 men).
2014-04-15 | E-GEOD-56686 | biostudies-arrayexpress