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PRMT5在胚胎发育停滞中的作用:来自体外受精-胚胎移植废弃人类胚胎的见解

The Role of PRMT5 in Embryonic Developmental Arrest: Insights from IVF-ET Discarded Human Embryos.

作者信息

Sun Ningyu, Li Shifeng, Li Kai, Yin Ping, Zhong Xiufang, Chen Yuanyuan, Lu Lu, Li Yun, Wu Yuanyuan, Yan Hua, Zhang Wuwen

机构信息

Department of Infertility and Reproductive Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No.528, Zhangheng Road, Pudong NewDistrict, Shanghai, 201203, China.

Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, 200031, China.

出版信息

Reprod Sci. 2025 Sep 18. doi: 10.1007/s43032-025-01957-w.

DOI:10.1007/s43032-025-01957-w
PMID:40968250
Abstract

Embryonic developmental arrest is a critical factor affecting the success rate of in vitro fertilization and embryo transfer (IVF-ET), and protein arginine methyltransferase 5 (PRMT5) plays a crucial role in early embryonic development. However, the mechanisms by which PRMT5 regulates embryonic development remain largely unexplored. Following the acquisition of informed consent from the patients, human embryos discarded from the IVF process were collected as experimental material. Real-time quantitative polymerase chain reaction (qRT-PCR) and confocal analysis were employed to quantify the levels of PRMT5 mRNA and protein at different developmental stages of early embryos, as well as to assess changes in H4R3me2s methylation levels. Furthermore, PRMT5 knockdown was performed in developmentally arrested embryos to observe its impact on further embryonic development. The results demonstrated a significant increase in both PRMT5 mRNA and protein levels in arrested embryos compared to control embryos. Additionally, a significant increase in the methylation level of H4R3me2s was observed in arrested embryos. The knockdown of PRMT5 has the potential to rescue some of the developmentally arrested embryos. In conclusion, the results of this study indicate that overexpression of PRMT5 leads to developmental arrest in early embryos, which can be partially rescued by knocking down the PRMT5 protein.

摘要

胚胎发育停滞是影响体外受精-胚胎移植(IVF-ET)成功率的关键因素,蛋白质精氨酸甲基转移酶5(PRMT5)在早期胚胎发育中起关键作用。然而,PRMT5调节胚胎发育的机制在很大程度上仍未得到探索。在获得患者知情同意后,收集IVF过程中丢弃的人类胚胎作为实验材料。采用实时定量聚合酶链反应(qRT-PCR)和共聚焦分析来量化早期胚胎不同发育阶段PRMT5 mRNA和蛋白质的水平,以及评估H4R3me2s甲基化水平的变化。此外,在发育停滞的胚胎中进行PRMT5基因敲低,以观察其对胚胎进一步发育的影响。结果表明,与对照胚胎相比,停滞胚胎中PRMT5 mRNA和蛋白质水平均显著增加。此外,在停滞胚胎中观察到H4R3me2s甲基化水平显著增加。敲低PRMT5有可能挽救一些发育停滞的胚胎。总之,本研究结果表明,PRMT5的过表达导致早期胚胎发育停滞,敲低PRMT5蛋白可部分挽救这种情况。

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本文引用的文献

1
Epigenetic regulation of early human embryo development.人类早期胚胎发育的表观遗传调控
Cell Stem Cell. 2023 Dec 7;30(12):1569-1584. doi: 10.1016/j.stem.2023.09.010. Epub 2023 Oct 18.
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Effectors and effects of arginine methylation.精氨酸甲基化的效应物和效应。
Biochem Soc Trans. 2023 Apr 26;51(2):725-734. doi: 10.1042/BST20221147.
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Novel histone post-translational modifications in diabetes and complications of diabetes: The underlying mechanisms and implications.糖尿病及并发症中新型组蛋白翻译后修饰:潜在机制与意义。
Biomed Pharmacother. 2022 Dec;156:113984. doi: 10.1016/j.biopha.2022.113984. Epub 2022 Nov 7.
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Klf4 methylated by Prmt1 restrains the commitment of primitive endoderm.PRMT1 甲基化 Klf4 抑制原始内胚层的特化。
Nucleic Acids Res. 2022 Feb 28;50(4):2005-2018. doi: 10.1093/nar/gkac054.
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Phenotypic drug screening in a human fibrosis model identified a novel class of antifibrotic therapeutics.在人类纤维化模型中进行的表型药物筛选鉴定出了一类新型抗纤维化治疗药物。
Sci Adv. 2021 Dec 24;7(52):eabb3673. doi: 10.1126/sciadv.abb3673. Epub 2021 Dec 22.
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Human embryonic development: from peri-implantation to gastrulation.人类胚胎发育:从着床前期到原肠胚形成期。
Trends Cell Biol. 2022 Jan;32(1):18-29. doi: 10.1016/j.tcb.2021.07.008. Epub 2021 Aug 17.
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The role of protein arginine methyltransferase 7 in human developmentally arrested embryos cultured in vitro.精氨酸甲基转移酶 7 在体外培养的人发育阻滞胚胎中的作用。
Acta Biochim Biophys Sin (Shanghai). 2021 Jul 5;53(7):925-932. doi: 10.1093/abbs/gmab068.
8
Protein arginine methylation: from enigmatic functions to therapeutic targeting.蛋白质精氨酸甲基化:从神秘功能到治疗靶点。
Nat Rev Drug Discov. 2021 Jul;20(7):509-530. doi: 10.1038/s41573-021-00159-8. Epub 2021 Mar 19.
9
The proteome of human Fallopian tube lavages during the phase of embryo transit reveals candidate proteins for the optimization of preimplantation embryo culture.人类输卵管灌洗液在胚胎转运阶段的蛋白质组学研究揭示了候选蛋白,可用于优化胚胎植入前的培养。
Hum Reprod. 2021 Jan 25;36(2):367-380. doi: 10.1093/humrep/deaa333.
10
Insights into epigenetic patterns in mammalian early embryos.哺乳动物早期胚胎中表观遗传模式的研究进展。
Protein Cell. 2021 Jan;12(1):7-28. doi: 10.1007/s13238-020-00757-z. Epub 2020 Jul 15.