Circulatory exosomal tRF-Glu-CTC-005 and tRF-Gly-GCC-002 serve as predictive factors of successful microdissection testicular sperm extraction in patients with nonobstructive azoospermia

In nonobstructive azoospermia patients with sperm retrieval by microsurgical testicular sperm extraction, successful ones expressed higher circulatory exosomal tRF-Gly-GCC-002 and tRF-Glu-CTC-005, suggesting which as potent predictors for residual sperm.

VOLUME 117, ISSUE 3, P512-521

Authors:

Qiang Zhang, Ph.D., Zhao Liu, M.S., Xiaoxiao Han, M.D., Ying Li, Ph.D., Tian Xia, B.S., Yao Zhu, B.S., Zhenbei Li, B.S., Liang Wang, Ph.D., Lin Hao, Ph.D., Fangfang Hu, M.S., Yijuan Cao, M.D., Conghui Han, M.D., Zuobin Zhu, Ph.D. 

Abstract:

Objective

To identify circulating plasma exosomal transfer RNA-derived fragments (tRFs) as the predictive factors of successful microdissection testicular sperm extraction (micro-TESE) in patients with nonobstructive azoospermia (NOA).


Design

Case and control prospective study.


Setting

Academic research laboratory.


Patient(s)

Twelve patients with NOA with successful sperm retrieval by micro-TESE, 18 patients with NOA with failed sperm retrieval by micro-TESE, and 12 normozoospermic fertile controls.


Intervention(s)

Blood samples were collected from participants.


Main Outcome Measure(s)

The abundance of tRFs normalized as counts per million of the total aligned reads with the next-generation sequencing system; candidate tRF levels were validated through quantitative reverse transcription polymerase chain reaction; predictive accuracy was evaluated by the receiver operating characteristic area under the curve analysis. The nomogram was built for ranking.


Result(s)

The plasma circulating exosomal tRF-Gly-GCC-002 and tRF-Glu-CTC-005 manifested the most confident differential expression between patients with NOA with successful sperm retrieval by micro-TESE and patients with NOA with failed sperm retrieval by micro-TESE. The target gene prediction of these 2 tRFs followed by the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis indicated the functional enrichment of neuroendocrine protein metabolism and striatum/subpallium development. The herpes simplex virus 1 infection pathway was also involved. The receiver operating characteristic area under the curve (AUC) analysis demonstrated a promising predictive accuracy: tRF-Gly-GCC-002, AUC of 0.921, and tRF-Glu-CTC-005, AUC of 0.954. A regression model was built and presented with the nomogram for further assessment.


Conclusion(s)

This study described the exosomal tRF-Gly-GCC-002 and tRF-Glu-CTC-005 expression values, indicated a promising predictive effect for accessibility of sperm retrieval through micro-TESE from patients with NOA, and highlighted tRF-Gly-GCC-002 and tRF-Glu-CTC-005 as useful biomarkers in patients with NOA seeking in vitro conception with their residual sperm.