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人类精子染色质的表观遗传潜能:基因组学、蛋白质组学与男性不育症

Human sperm chromatin epigenetic potential: genomics, proteomics, and male infertility.

作者信息

Castillo Judit, Estanyol Josep Maria, Ballescá Josep Lluis, Oliva Rafael

机构信息

Human Genetics Research Group, IDIBAPS, Faculty of Medicine, University of Barcelona, Casanova 143; Biochemistry and Molecular Genetics Service, Biomedical Diagnostic Centre, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain.

出版信息

Asian J Androl. 2015 Jul-Aug;17(4):601-9. doi: 10.4103/1008-682X.153302.

DOI:10.4103/1008-682X.153302
PMID:25926607
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4492051/
Abstract

The classical idea about the function of the mammalian sperm chromatin is that it serves to transmit a highly protected and transcriptionally inactive paternal genome, largely condensed by protamines, to the next generation. In addition, recent sperm chromatin genome-wide dissection studies indicate the presence of a differential distribution of the genes and repetitive sequences in the protamine-condensed and histone-condensed sperm chromatin domains, which could be potentially involved in regulatory roles after fertilization. Interestingly, recent proteomic studies have shown that sperm chromatin contains many additional proteins, in addition to the abundant histones and protamines, with specific modifications and chromatin affinity features which are also delivered to the oocyte. Both gene and protein signatures seem to be altered in infertile patients and, as such, are consistent with the potential involvement of the sperm chromatin landscape in early embryo development. This present work reviews the available information on the composition of the human sperm chromatin and its epigenetic potential, with a particular focus on recent results derived from high-throughput genomic and proteomic studies. As a complement, we provide experimental evidence for the detection of phosphorylations and acetylations in human protamine 1 using a mass spectrometry approach. The available data indicate that the sperm chromatin is much more complex than what it was previously thought, raising the possibility that it could also serve to transmit crucial paternal epigenetic information to the embryo.

摘要

关于哺乳动物精子染色质功能的经典观点是,它用于将高度受保护且转录无活性的父本基因组传递给下一代,该基因组主要由鱼精蛋白凝聚而成。此外,最近的精子染色质全基因组剖析研究表明,在鱼精蛋白凝聚和组蛋白凝聚的精子染色质结构域中,基因和重复序列存在差异分布,这可能在受精后发挥调控作用。有趣的是,最近的蛋白质组学研究表明,除了丰富的组蛋白和鱼精蛋白外,精子染色质还含有许多其他蛋白质,这些蛋白质具有特定的修饰和染色质亲和特性,也会传递给卵母细胞。不育患者的基因和蛋白质特征似乎都发生了改变,因此,这与精子染色质格局在早期胚胎发育中的潜在作用是一致的。本研究综述了关于人类精子染色质组成及其表观遗传潜力的现有信息,特别关注了高通量基因组和蛋白质组学研究的最新结果。作为补充,我们提供了使用质谱方法检测人类鱼精蛋白1磷酸化和乙酰化的实验证据。现有数据表明,精子染色质比之前认为的要复杂得多,这增加了它也可能将关键的父本表观遗传信息传递给胚胎的可能性。

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本文引用的文献

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The specification and global reprogramming of histone epigenetic marks during gamete formation and early embryo development in C. elegans.秀丽隐杆线虫配子形成和早期胚胎发育过程中组蛋白表观遗传标记的特异性及全局重编程
PLoS Genet. 2014 Oct 9;10(10):e1004588. doi: 10.1371/journal.pgen.1004588. eCollection 2014 Oct.
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Sperm epigenomics: challenges and opportunities.精子表观基因组学:挑战与机遇。
Front Genet. 2014 Sep 18;5:330. doi: 10.3389/fgene.2014.00330. eCollection 2014.
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Genomic and proteomic dissection and characterization of the human sperm chromatin.
精子中较高的组蛋白H3赖氨酸4三甲基化(H3K4me3)水平与特发性复发性流产相关。
Epigenetics. 2025 Dec;20(1):2498859. doi: 10.1080/15592294.2025.2498859. Epub 2025 Apr 29.
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The microbiota: a key regulator of health, productivity, and reproductive success in mammals.微生物群:哺乳动物健康、生产力和繁殖成功的关键调节因子。
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Adverse Effects of Nicotine on Human Sperm Nuclear Proteins.尼古丁对人类精子核蛋白的不良影响。
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Variations in Sperm DNA and Its Correlation to Pregnancy.精子 DNA 变异及其与妊娠的关系。
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Sperm epigenetics and male infertility: unraveling the molecular puzzle.精子表观遗传学与男性不育:揭开分子谜题。
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A critical review of the recent concept of regulatory performance of DNA Methylations, and DNA methyltransferase enzymes alongside the induction of immune microenvironment elements in recurrent pregnancy loss.对DNA甲基化的调控性能、DNA甲基转移酶以及复发性流产中免疫微环境元素诱导的最新概念进行批判性综述。
Toxicol Rep. 2024 May 9;12:546-563. doi: 10.1016/j.toxrep.2024.05.001. eCollection 2024 Jun.
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Genes (Basel). 2024 Apr 7;15(4):464. doi: 10.3390/genes15040464.
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