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Biomarkers in semen/urine from non-obstructive azoospermia patients to predict the presence of testicular spermatozoa and spermatogonia

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE224511 | GEO | 2023/02/06

REPOSITORIES: GEO

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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.

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Biomarkers in semen/urine from non-obstructive azoospermia patients to predict the presence of testicular spermatozoa and spermatogonia

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