MicroRNA profile comparison of testicular tissues derived from successful and unsuccessful microdissection testicular sperm extraction retrieval in non-obstructive azoospermia patients
MicroRNA profile comparison of testicular tissues derived from successful and unsuccessful microdissection testicular sperm extraction retrieval in non-obstructive azoospermia patients
复制标题
非梗阻性无精症患者成功和不成功的显微解剖睾丸取精术中睾丸组织的 MicroRNA 谱比较
DOI：
10.1071/rd17423
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发表时间：
2019-03-01
影响因子：
1.9
通讯作者：
Huang, Xunbin
中科院分区：
文献类型：
--
作者：
Fang, Na;Cao, Congcong;Huang, Xunbin
非梗阻性无精子症(NOA)是男性不育患者中最严重的临床诊断。虽然在某些NOA病例中，可以通过显微分离睾丸精子提取(Micro-TESE)通过卵胞浆内单精子注射(ICSI)受精卵来获取精子，但在Micro-TESE手术前仍缺乏潜在的非侵入性诊断生物标志物。为了在微TESE前确定成功取精的预测生物标志物，本研究的目的是利用下一代小RNA测序(RNA-Seq)技术，探讨在取精成功(SSR)和取精不成功(USR)的NOA患者睾丸组织中，microRNAs(MiRNAs)的表达是否存在差异。总共鉴定了180个miRNAs，它们在SSR和USR睾丸组织中的表达水平有显著差异。其中，与SSR组相比，USR组有13个miRNAs表达上调，167个miRNAs表达下调。出人意料的是，在USR组中发现86个睾丸miRNAs完全缺失，而在SSR组中却有高表达，这表明这些miRNAs可能作为microTESE的生物标志物，也可能在精子发生中发挥重要作用。此外，基因本体论(GO)和京都基因和基因组百科全书(KEGG)途径分析表明，USR组和SSR组之间明显不同的miRNAs参与了细胞的凋亡、增殖和分化，这在精子发生过程中具有相当重要的作用。综上所述，本研究发现了一组在SSR而不是NOA患者的睾丸组织中高表达的miRNAs，为了解特定的miRNAs可能在精子发生过程中的表观遗传调控中发挥重要作用提供了新的见解。这些发现为进一步阐明miRNAs在精子发生中的调控作用提供了基础，并为寻找有用的生物标记物来预测辅助生殖技术治疗期间NOA患者的残余生精基因提供了线索。
Non-obstructive azoospermia (NOA) is the most severe clinical diagnosis in cases of male infertility. Although in some cases of NOA spermatozoa can be retrieved by microdissection testicular sperm extraction (micro-TESE) to fertilise eggs through intracytoplasmic sperm injection (ICSI), there remains a lack of potential biomarkers for non-invasive diagnosis before micro-TESE surgery. To determine predictive biomarkers for successful sperm retrieval before micro-TESE, the aim of this study was to explore whether microRNAs (miRNAs) were differentially expressed in testicular tissues in NOA patients in whom sperm retrieval had been successful (SSR) versus those in whom it had been unsuccessful (USR) using next-generation small RNA sequencing (RNA-Seq). In all, 180 miRNAs were identified with significantly altered expression levels between SSR and USR testicular tissues. Of these, the expression of 13 miRNAs was upregulated and that of 167 miRNAs was downregulated in the USR compared with SSR group. Unexpectedly, 86 testicular miRNAs were found to be completely absent in the USR group, but showed high expression in the SSR group, suggesting that these miRNAs may serve as biomarkers for micro-TESE and may also play an essential role in spermatogenesis. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that the miRNAs that differed significantly between the USR and SSR groups were involved in cell apoptosis, proliferation and differentiation, which are of considerable importance during spermatogenesis. In summary, this study identified a panel of miRNAs highly expressed in testicular tissues of SSR but not USR NOA patients, providing new insights into specific miRNAs that may play important roles in epigenetic regulation during spermatogenesis. The findings provide a basis for further elucidation of the regulatory role of miRNAs in spermatogenesis and clues to identifying useful biomarkers to predict residual spermatogenic loci in NOA patients during treatment with assisted reproductive technologies.