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piRNAs 在介导哺乳动物精子发生中的功能和机制及其在生殖医学中的应用。

The functions and mechanisms of piRNAs in mediating mammalian spermatogenesis and their applications in reproductive medicine.

机构信息

The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, The Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University School of Medicine, The Manufacture-Based Learning and Research Demonstration Center for Human Reproductive Health New Technology of Hunan Normal University, Changsha, 410013, China.

Shanghai Key Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

出版信息

Cell Mol Life Sci. 2024 Sep 2;81(1):379. doi: 10.1007/s00018-024-05399-6.

DOI:10.1007/s00018-024-05399-6
PMID:39222270
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11369131/
Abstract

As the most abundant small RNAs, piwi-interacting RNAs (piRNAs) have been identified as a new class of non-coding RNAs with 24-32 nucleotides in length, and they are expressed at high levels in male germ cells. PiRNAs have been implicated in the regulation of several biological processes, including cell differentiation, development, and male reproduction. In this review, we focused on the functions and molecular mechanisms of piRNAs in controlling spermatogenesis, including genome stability, regulation of gene expression, and male germ cell development. The piRNA pathways include two major pathways, namely the pre-pachytene piRNA pathway and the pachytene piRNA pathway. In the pre-pachytene stage, piRNAs are involved in chromosome remodeling and gene expression regulation to maintain genome stability by inhibiting transposon activity. In the pachytene stage, piRNAs mediate the development of male germ cells via regulating gene expression by binding to mRNA and RNA cleavage. We further discussed the correlations between the abnormalities of piRNAs and male infertility and the prospective of piRNAs' applications in reproductive medicine and future studies. This review provides novel insights into mechanisms underlying mammalian spermatogenesis and offers new targets for diagnosing and treating male infertility.

摘要

作为最丰富的小 RNA 之一,piwi 相互作用 RNA (piRNAs) 已被确定为一类新的非编码 RNA,长度为 24-32 个核苷酸,在雄性生殖细胞中高水平表达。piRNAs 参与了几个生物学过程的调节,包括细胞分化、发育和雄性生殖。在这篇综述中,我们重点介绍了 piRNAs 在控制精子发生中的功能和分子机制,包括基因组稳定性、基因表达调控和雄性生殖细胞发育。piRNA 途径包括两个主要途径,即前期 piRNA 途径和粗线期 piRNA 途径。在前期阶段,piRNAs 参与染色体重塑和基因表达调控,通过抑制转座子活性来维持基因组稳定性。在粗线期,piRNAs 通过与 mRNA 结合和 RNA 切割来调节基因表达,从而介导雄性生殖细胞的发育。我们进一步讨论了 piRNAs 异常与男性不育之间的相关性,以及 piRNAs 在生殖医学和未来研究中应用的前景。本综述为哺乳动物精子发生的机制提供了新的见解,并为男性不育的诊断和治疗提供了新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6cb/11369131/22a5541d9773/18_2024_5399_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6cb/11369131/98b43dd0f000/18_2024_5399_Figa_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6cb/11369131/0f5e55711745/18_2024_5399_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6cb/11369131/2a3f215e5acf/18_2024_5399_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6cb/11369131/22a5541d9773/18_2024_5399_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6cb/11369131/98b43dd0f000/18_2024_5399_Figa_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6cb/11369131/0f5e55711745/18_2024_5399_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6cb/11369131/2a3f215e5acf/18_2024_5399_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6cb/11369131/22a5541d9773/18_2024_5399_Fig3_HTML.jpg

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Two RNA binding proteins, ADAD2 and RNF17, interact to form a heterogeneous population of novel meiotic germ cell granules with developmentally dependent organelle association.两个 RNA 结合蛋白,ADAD2 和 RNF17,相互作用形成了一种具有发育依赖性细胞器关联的新型减数分裂生殖细胞颗粒的异质群体。
PLoS Genet. 2023 Jul 10;19(7):e1010519. doi: 10.1371/journal.pgen.1010519. eCollection 2023 Jul.
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The PIWI-specific insertion module helps load longer piRNAs for translational activation essential for male fertility.
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Int J Mol Sci. 2025 Apr 9;26(8):3537. doi: 10.3390/ijms26083537.
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Epigenetic Alterations in Ovarian Function and Their Impact on Assisted Reproductive Technologies: A Systematic Review.卵巢功能的表观遗传改变及其对辅助生殖技术的影响:一项系统综述。
Biomedicines. 2025 Mar 17;13(3):730. doi: 10.3390/biomedicines13030730.
PIWI 特异性插入模块有助于加载更长的 piRNA,从而进行翻译激活,这对于雄性育性至关重要。
Sci China Life Sci. 2023 Jul;66(7):1459-1481. doi: 10.1007/s11427-023-2390-5. Epub 2023 Jun 15.
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