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.

中文翻译：

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循环外泌体 tRF-Glu-CTC-005 和 tRF-Gly-GCC-002 作为非梗阻性无精子症患者成功显微解剖睾丸精子提取的预测因素

客观的

确定循环血浆外泌体转移 RNA 衍生片段 (tRF) 作为非梗阻性无精子症 (NOA) 患者成功显微解剖睾丸精子提取 (micro-TESE) 的预测因素。

设计

案例和对照前瞻性研究。

环境

学术研究实验室。

患者）

12 名 NOA 患者通过微型 TESE 成功取精，18 名 NOA 患者通过微型 TESE 取精失败，12 名正常精子可育对照。

干预措施

从参与者身上采集了血样。

主要观察指标）

使用下一代测序系统将 tRF 的丰度标准化为总比对读数的每百万计数；通过定量逆转录聚合酶链反应验证候选 tRF 水平；通过曲线分析下的接受者操作特征面积评估预测准确性。列线图是为排名而构建的。

结果）

血浆循环外泌体 tRF-Gly-GCC-002 和 tRF-Glu-CTC-005 在微 TESE 取精成功的 NOA 患者和微 TESE 取精失败的 NOA 患者之间表现出最可信的差异表达。这 2 个 tRF 的靶基因预测以及基因本体论和京都基因和基因组百科全书分析表明神经内分泌蛋白代谢和纹状体/大脑皮下层发育的功能丰富。单纯疱疹病毒 1 型感染途径也参与其中。接受者操作曲线下的特征区域 (AUC) 分析表明预测准确性很有前途：tRF-Gly-GCC-002，AUC 为 0.921，tRF-Glu-CTC-005，AUC 为 0.954。建立了一个回归模型，并与列线图一起呈现以供进一步评估。

结论

本研究描述了外泌体 tRF-Gly-GCC-002 和 tRF-Glu-CTC-005 表达值，表明通过微 TESE 从 NOA 患者中提取精子的可及性具有良好的预测效果，并强调了 tRF-Gly-GCC- 002 和 tRF-Glu-CTC-005 作为 NOA 患者寻求用其残留精子进行体外受孕的有用生物标志物。