经体外受精治疗的精液质量差的男性精浆外泌体中改变的非编码 RNA 谱。
Altered non-coding RNA profiles of seminal plasma extracellular vesicles of men with poor semen quality undergoing in vitro fertilization treatment.
机构信息
Department of Obstetrics and Gynecology, C.S. Mott Center for Human Growth and Development, School of Medicine, Wayne State University, Detroit, Michigan, USA.
Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, Massachusetts, USA.
出版信息
Andrology. 2023 May;11(4):677-686. doi: 10.1111/andr.13295. Epub 2022 Oct 2.
BACKGROUND
Currently, the precise mechanisms that underline male infertility are still unclear. Accumulating data implicate non-coding RNA cargo of seminal plasma extracellular vesicles due to their association with poor semen quality and higher expression levels relative to vesicle-free seminal plasma.
METHOD
We assessed sperm-free seminal plasma extracellular vesicle non-coding RNA profiles from 91 semen samples collected from male participants of couples seeking infertility treatment. Men were classified into two groups (poor, n = 32; normal, n = 59) based on World Health Organization semen cutoffs. Small RNA sequencing reads were mapped to standard biotype-specific transcriptomes in the order micro RNA > transfer RNA > piwi-interacting RNA > ribosomal RNA > ribosomal RNA > circular RNA > long non-coding RNA using STAR. Differential expression of normalized non-coding RNA read counts between the two groups was conducted by EdgeR (Fold change ≥1.5 and (false discovery rate [FDR] < 0.05).
RESULT
Small RNA sequencing identified a wide variety of seminal plasma extracellular vesicle non-coding RNA biotypes including micro RNA, ribosomal RNAs, piwi-interacting RNAs, transfer RNA, long non-coding RNAs as well as circular RNAs, and fragments associated with pseudogenes, and nonsense-mediated decay. The expression levels of 57 seminal plasma extracellular vesicle non-coding RNAs (micro RNA: 6, piwi-interacting RNA: 4, ribosomal RNA: 6, circular RNA: 34, and long non-coding RNA: 7) were altered in men with poor semen quality relative to normal semen parameters, many (60%) of which were circular RNA species. Ontology analysis of differentially expressed micro RNAs and circular RNAs showed enrichment in functional terms related to cellular communication and early development.
CONCLUSION
This is the first study to generate comprehensive seminal plasma extracellular vesicle non-coding RNA profiles in a clinical setting and to determine the differences between men with normal and abnormal semen parameters. Thus, our study suggests that seminal plasma extracellular vesicle non-coding RNAs may represent novel biomarkers of male reproductive phenotypes.
背景
目前，男性不育的确切机制仍不清楚。越来越多的数据表明，由于与精液质量差有关，并且相对于无囊泡精液，囊泡外泌体中非编码 RNA 的表达水平更高，因此非编码 RNA 是精液外泌体的主要成分。
方法
我们评估了 91 例寻求不孕治疗的夫妇中男性参与者的精子游离精液外泌体非编码 RNA 图谱。根据世界卫生组织的精液标准，将男性分为两组（差，n=32；正常，n=59）。使用 STAR 将小 RNA 测序读取映射到标准生物型特异性转录组中，顺序为 micro RNA>转移 RNA>piwi 相互作用 RNA>核糖体 RNA>核糖体 RNA>环状 RNA>长非编码 RNA。使用 EdgeR（差异倍数≥1.5 和（错误发现率[FDR]<0.05）对两组之间的非编码 RNA 读数计数进行差异表达。
结果
小 RNA 测序确定了广泛的精液外泌体非编码 RNA 生物类型，包括 micro RNA、核糖体 RNA、piwi 相互作用 RNA、转移 RNA、长非编码 RNA 以及环状 RNA 和与假基因和无义介导的降解相关的片段。与正常精液参数相比，精液质量差的男性中 57 种精液外泌体非编码 RNA（micro RNA：6，piwi 相互作用 RNA：4，核糖体 RNA：6，环状 RNA：34，长非编码 RNA：7）的表达水平发生改变，其中许多（60%）为环状 RNA 物种。差异表达的 micro RNA 和环状 RNA 的本体论分析显示，与细胞通讯和早期发育相关的功能术语富集。
结论
这是首次在临床环境中生成全面的精液外泌体非编码 RNA 图谱，并确定正常和异常精液参数男性之间的差异。因此，我们的研究表明，精液外泌体非编码 RNA 可能代表男性生殖表型的新型生物标志物。
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