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人类精子tsRNA作为男性生育力的潜在生物标志物和治疗靶点。

Human sperm tsRNA as potential biomarker and therapy target for male fertility.

作者信息

Chen Xiaoxu, Sun Qian, Zheng Yi, Liu Zidong, Meng Xiangqian, Zeng Wenxian, Lu Hongzhao

机构信息

College of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong, China.

Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.

出版信息

Reproduction. 2021 Feb;161(2):111-122. doi: 10.1530/REP-20-0415.

DOI:10.1530/REP-20-0415
PMID:33434159
Abstract

Infertility caused by male factors is routinely diagnosed by assessing traditional semen parameters. Growing evidence has indicated that the tsRNAs carried in sperm act as epigenetic factors and potential biomarkers for the assessment of sperm quality. We recently demonstrated that tRNAGln-TTG derived small RNAs played notable roles in the first cleavage of a porcine embryo. However, the function of human sperm tRNAGln-TTG derived small RNAs as a diagnostic biomarker and its role in early embryo development remains unclear. In this study, we found that human sperm tRNAGln-TTG derived small RNAs were highly associated with sperm quality. By microinjecting the antisense sequence into human tripronuclear (3PN) zygotes followed by single-cell RNA-sequencing, we found that human sperm tRNAGln-TTG derived small RNAs participated in the development of a human embryo. Furthermore, Gln-TTGs might influence embryonic genome activation by modulating noncoding RNA processing. These findings demonstrated that human sperm tRNAGln-TTG derived small RNAs could be potential diagnostic biomarkers and could be used as a clinical target for male infertility.

摘要

男性因素导致的不育通常通过评估传统精液参数来诊断。越来越多的证据表明,精子中携带的tsRNAs作为表观遗传因子和评估精子质量的潜在生物标志物。我们最近证明,tRNAGln-TTG衍生的小RNA在猪胚胎的第一次卵裂中发挥了显著作用。然而,人类精子tRNAGln-TTG衍生的小RNA作为诊断生物标志物的功能及其在早期胚胎发育中的作用仍不清楚。在本研究中,我们发现人类精子tRNAGln-TTG衍生的小RNA与精子质量高度相关。通过将反义序列显微注射到人类三原核(3PN)合子中,然后进行单细胞RNA测序,我们发现人类精子tRNAGln-TTG衍生的小RNA参与了人类胚胎的发育。此外,Gln-TTGs可能通过调节非编码RNA加工来影响胚胎基因组激活。这些发现表明,人类精子tRNAGln-TTG衍生的小RNA可能是潜在的诊断生物标志物,可作为男性不育的临床靶点。

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