Journal of assisted reproduction and genetics
August 20, 2026 · via Europe PMC
Circular RNA-Mediated ceRNA networks predict sperm retrieval outcomes in non-obstructive azoospermia.
Babakhanzadeh E, Khodadadian A, Nazari M, +5 more, Ghasemi N.
AI summary — for doctors, generated from the abstract only
Two circRNA-miRNA-mRNA regulatory axes were dysregulated in non-obstructive azoospermia, more so in men with failed sperm retrieval, and showed high discrimination for mTESE outcome.
What was studied
An integrative bioinformatics and experimental validation study of the circSH3PXD2A/miR-375-3p/SH3PXD2A and hsa_circ_0037070/miR-487b-3p/ALDH1A3 axes in NOA patients.
Key findings
- SH3PXD2A and ALDH1A3 upregulated in NOA, with their regulatory miRNAs downregulated
- circRNA partners showed subtype-specific changes
- Dysregulation was more extreme in men with failed sperm retrieval
- circRNAs and miRNAs showed AUC >0.90 for discrimination
Clinical relevance
These RNA markers may become minimally invasive predictors of sperm retrieval success, but external validation is needed before clinical use.
Who should care
Limitations
Sample size and cohort details are not reported in the abstract, and very high AUCs from a discovery setting risk overfitting.
Circulating circRNA and miRNA signatures are promising candidates for predicting sperm retrieval in NOA.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Introduction
Non-obstructive azoospermia (NOA) is a severe form of male infertility in which focal spermatogenesis may persist in otherwise functionally impaired testes. Testicular sperm extraction by microdissection (mTESE) remains the standard procedure for sperm retrieval, but its unpredictable success rate emphasizes the urgent need for reliable, non-invasive biomarkers to support clinical decision-making. Recent advances in transcriptomics have highlighted the role of circular RNAs (circRNAs), microRNAs (miRNAs), and their mRNA targets in the formation of competing endogenous RNA networks (ceRNAs) that regulate spermatogenesis.
Methods
In this study, we identified and validated two novel ceRNA axes, circSH3PXD2A/miR-375-3p/SH3PXD2A and hsa_circ_0037070/miR-487b-3p/ALDH1A3, by integrative bioinformatics and experimental analyses.
Results
Both SH3PXD2A and ALDH1A3 were significantly upregulated in NOA patients, while their regulatory miRNAs were downregulated, with circRNA partners showing subtype-specific changes. Importantly, the differences in expression correlated with the mTESE results: NOA - patients (failed recovery) showed more extreme dysregulation than NOA + . Receiver operating characteristic (ROC) curve analysis confirmed the diagnostic potential of these markers, with circRNAs and miRNAs showing high discriminatory power (AUC > 0.90).
Conclusion
Our results demonstrate that dysregulation of circRNA-miRNA-mRNA networks is a key feature of NOA and that circulating circRNAs and miRNAs can serve as minimally invasive biomarkers for predicting sperm retrieval success. These findings not only improve our understanding of the molecular basis of NOA, but also open up new avenues for precision diagnostics in male infertility.
DOI
10.1007/s10815-026-04013-x
PMID
42623004
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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