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基于 miRNA 测序的精子 DNA 损伤机制研究。

A Study of Sperm DNA Damage Mechanism Based on miRNA Sequencing.

机构信息

Henan University of Chinese Medicine, Zhengzhou, China.

Department of Andrology, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.

出版信息

Am J Mens Health. 2024 Sep-Oct;18(5):15579883241286672. doi: 10.1177/15579883241286672.

DOI:10.1177/15579883241286672
PMID:39462893
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11528732/
Abstract

To analyze the differential expression profiles of microRNAs (miRNAs) in spermatozoa of patients with sperm DNA damage and to investigate the role of miRNAs in sperm DNA damage. Male infertility patients with sperm DNA damage who attended the First Affiliated Hospital of Henan University of Chinese Medicine from October 2023 to December 2023 were selected and included in this study as a case group. Fertile healthy men who were seen at the health check-up center during the same period and diagnosed by examination were also included as a control group. Sperm miRNA expression was detected in patients with sperm DNA damage (case group, = 5) and healthy medical check-ups (control group, = 5) using high-throughput sequencing technology. The differentially expressed miRNAs between the two groups were bioinformatically analyzed to explore the main biological functions of the target genes. We found that 63 miRNAs were significantly changed in the spermatozoa of patients with sperm DNA damage,|log2 (foldchange)| ≥ 1, < .05. Gene Ontology (GO) enrichment analysis indicated that these differential miRNAs might be involved in developmental process, anatomical structure development, cellular macromolecule metabolic process, multicellular organism development, system development, and so on. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that that they mainly affect the PI3K-AKT signaling pathway. The present study suggests that the altered expression of miR-1255a, miR-921, and miR-3156-5p may play an important role in the sperm DNA damage process, and the mechanism may involve the phosphatidylinositol-3'-kinase-AKT (PI3K-AKT) signaling pathway.

摘要

分析精子 DNA 损伤患者精子中 microRNAs (miRNAs) 的差异表达谱,并探讨 miRNAs 在精子 DNA 损伤中的作用。选择 2023 年 10 月至 12 月在河南中医药大学第一附属医院就诊的精子 DNA 损伤的男性不育患者作为病例组,并纳入研究。同时纳入同期在健康体检中心体检、经检查诊断为健康的男性作为对照组。采用高通量测序技术检测精子 DNA 损伤患者(病例组,n = 5)和健康体检者(对照组,n = 5)的精子 miRNA 表达。对两组间差异表达的 miRNAs 进行生物信息学分析,以探讨靶基因的主要生物学功能。结果发现,精子 DNA 损伤患者精子中 63 个 miRNAs 表达明显改变,|log2(foldchange)|≥1,P<0.05。基因本体论(GO)富集分析表明,这些差异表达的 miRNAs 可能参与发育过程、解剖结构发育、细胞大分子代谢过程、多细胞生物发育、系统发育等。京都基因与基因组百科全书(KEGG)富集分析显示,它们主要影响 PI3K-AKT 信号通路。本研究提示 miR-1255a、miR-921 和 miR-3156-5p 的表达改变可能在精子 DNA 损伤过程中发挥重要作用,其机制可能涉及磷脂酰肌醇-3'-激酶-AKT(PI3K-AKT)信号通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd1/11528732/7366acca8681/10.1177_15579883241286672-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd1/11528732/ee0fd193f7ef/10.1177_15579883241286672-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd1/11528732/cc11c481345c/10.1177_15579883241286672-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd1/11528732/7366acca8681/10.1177_15579883241286672-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd1/11528732/ee0fd193f7ef/10.1177_15579883241286672-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd1/11528732/cc11c481345c/10.1177_15579883241286672-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd1/11528732/7366acca8681/10.1177_15579883241286672-fig3.jpg

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本文引用的文献

1
High sperm DNA fragmentation: do we have robust evidence to support antioxidants and testicular sperm extraction to improve fertility outcomes? a narrative review.精子 DNA 碎片化程度高:我们有充分的证据支持抗氧化剂和睾丸精子提取术来改善生育结局吗?一篇叙述性综述。
Front Endocrinol (Lausanne). 2023 Oct 5;14:1150951. doi: 10.3389/fendo.2023.1150951. eCollection 2023.
2
The Impact of Oxidative Stress on Male Reproductive Function: Exploring the Role of Antioxidant Supplementation.氧化应激对男性生殖功能的影响:探索抗氧化剂补充剂的作用
Cureus. 2023 Jul 27;15(7):e42583. doi: 10.7759/cureus.42583. eCollection 2023 Jul.
3
GPx3 knockdown inhibits the proliferation and DNA synthesis and enhances the early apoptosis of human spermatogonial stem cells via mediating CXCL10 and cyclin B1.
GPx3基因敲低通过介导CXCL10和细胞周期蛋白B1抑制人精原干细胞的增殖和DNA合成,并增强其早期凋亡。
Front Cell Dev Biol. 2023 Jul 7;11:1213684. doi: 10.3389/fcell.2023.1213684. eCollection 2023.
4
Repair mechanism of Yishen Tongluo formula on mouse sperm DNA fragmentation caused by polystyrene microplastics.益肾通络方修复聚苯乙烯微塑料致小鼠精子 DNA 碎片化的作用机制。
Pharm Biol. 2023 Dec;61(1):488-498. doi: 10.1080/13880209.2023.2168705.
5
Transcriptomic and proteomic characteristics of the di(2-ethylhexyl) phthalate-induced sperm dna damage mouse model.邻苯二甲酸二(2-乙基己基)酯致精子 DNA 损伤小鼠模型的转录组学和蛋白质组学特征。
Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221139444. doi: 10.1177/09603271221139444.
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[Molecular mechanisms of male infertility: main directions of scientific research].[男性不育的分子机制:科学研究的主要方向]
Urologiia. 2022 Sep(4):114-117.
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GM-CSF (granulocyte-macrophage colony-stimulating factor) treatment improves sperm parameters in men with oligoasthenoteratospermia via PI3K/AKT pathway.粒细胞-巨噬细胞集落刺激因子(GM-CSF)治疗通过PI3K/AKT途径改善少弱畸精子症男性的精子参数。
Andrologia. 2022 Aug;54(7):1618-1630. doi: 10.1111/and.14427. Epub 2022 May 11.
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The Role of Seminal Oxidative Stress Scavenging System in the Pathogenesis of Sperm DNA Damage in Men Exposed and Not Exposed to Genital Heat Stress.精液氧化应激清除系统在暴露和未暴露于生殖热应激男性精子 DNA 损伤发病机制中的作用。
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HPV-mediated regulation of SMAD4 modulates the DNA damage response in head and neck cancer.HPV 介导的 SMAD4 调节在头颈部癌症中的 DNA 损伤反应。
J Exp Clin Cancer Res. 2022 Feb 10;41(1):59. doi: 10.1186/s13046-022-02258-9.
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miR-125a-5p increases cellular DNA damage of aging males and perturbs stage-specific embryo development via Rbm38-p53 signaling.miR-125a-5p 通过 Rbm38-p53 信号增加衰老雄性细胞的 DNA 损伤,并扰乱胚胎发育的特定阶段。
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