Related Experiment Video
Updated: May 28, 2026
Flow Cytometric Analysis of Biomarkers for Detecting Human Sperm Functional Defects
Published on: April 21, 2022
A novel hsa_circ_0070963/miR-223-3p/ CCDC96-CCDC112 regulatory axis as a non-invasive biomarker for predicting sperm
Emad Babakhanzadeh1,2, Ali Khodadadian2, Majid Nazari2
1Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Background:
Non-obstructive azoospermia (NOA) is a severe cause of male infertility. Testicular sperm extraction has limited success, largely due to the absence of reliable, non-invasive biomarkers to predict outcomes. Emerging evidence highlights the role of non-coding RNAs in spermatogenesis, providing promising targets for biomarker development.
Objective:
This study investigated the competing endogenous RNA regulatory axis hsa_circ_0070963/miR-223-3p/CCDC96-CCDC112 as a potential biomarker for predicting microsurgical testicular sperm extraction (micro-TESE) outcomes in NOA individuals.
Materials And Methods:
In this case-control study, 60 men with NOA undergoing micro-TESE and 40 fertile controls were recruited. Testicular histology categorized individuals into Sertoli cell-only syndrome, hypospermatogenesis, or maturation arrest. Individuals were further stratified into NOA⁺ (successful retrieval) and NOA⁻ (failed retrieval). Plasma RNA was extracted, and expression levels of candidate genes were measured by quantitative reverse transcription polymerase chain reaction.
Results:
Findings demonstrated significant downregulation of CCDC96 and CCDC112 in NOA plasma, particularly in NOA⁻ individuals, while hsa-miR-223-3p was upregulated, with the highest expression in NOA⁻ cases. Conversely, hsa_circ_0070963 was markedly reduced in NOA, especially in NOA⁻ individuals. Dysregulation was more pronounced in hypospermatogenesis and maturation arrest compared to Sertoli cell-only syndrome. Receiver operating characteristic analysis revealed strong predictive accuracy, with hsa_circ_0070963 (area under the receiver operating characteristic curve = 0.983) and hsa-miR-223-3p (area under the curve = 0.970) outperforming CCDC96 and CCDC112.
Conclusion:
hsa_circ_0070963/miR-223-3p/CCDC96-CCDC112 axis represents a novel competing endogenous RNAs regulatory network linked to impaired spermatogenesis. Its expression profile provides mechanistic insights and serves as a robust, non-invasive biomarker for predicting micro-TESE outcomes, supporting improved stratification and individualized treatment strategies in male infertility.
