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IZUMO1 依赖性精子配子融合影响小鼠的雄性生育能力。

Sperm IZUMO1-Dependent Gamete Fusion Influences Male Fertility in Mice.

机构信息

Department of Cell Science, Institute of Biomedical Sciences, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima City, Fukushima 960-1295, Japan.

出版信息

Int J Mol Sci. 2019 Sep 27;20(19):4809. doi: 10.3390/ijms20194809.

DOI:10.3390/ijms20194809
PMID:31569716
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6801368/
Abstract

Sperm-egg fusion is accomplished through the interaction of a specific set of membrane proteins in each gamete: sperm IZUMO1 and oocyte JUNO. Recently, we found that alternative splicing of the gene generates a novel IZUMO1 isoform (IZUMO1_v2). Here, we obtained four mouse lines, having graded different levels of IZUMO1 protein by combining an original IZUMO1 (IZUMO1_v1) knockout with IZUMO1-null (both IZUMO1_v1 and _v2 disrupted) genetic background, in order to determine how the quantity of IZUMO1 influences male fertility. Subsequently, we clarified that the signal intensity from two quantitative assays, western blot and immunostaining analyses with a monoclonal antibody against mouse IZUMO1, were strongly correlated with average litter size. These results suggest that evaluating IZUMO1 protein levels is useful for predicting fecundity, and is a suitable test for male fertility.

摘要

精卵融合是通过每个配子中一组特定的膜蛋白相互作用完成的

精子 IZUMO1 和卵子 JUNO。最近,我们发现基因的可变剪接产生了一种新的 IZUMO1 同工型(IZUMO1_v2)。在这里,我们获得了四条鼠系,通过将原始 IZUMO1(IZUMO1_v1)敲除与 IZUMO1 缺失(IZUMO1_v1 和 _v2 均被破坏)遗传背景相结合,产生了不同程度的 IZUMO1 蛋白,以确定 IZUMO1 的数量如何影响雄性生育能力。随后,我们阐明了两种定量检测方法的信号强度,即western blot 和针对小鼠 IZUMO1 的单克隆抗体的免疫染色分析,与平均产仔数呈强相关。这些结果表明,评估 IZUMO1 蛋白水平有助于预测生育能力,是一种适合男性生育力的检测方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/761c/6801368/5ec2ae75fde3/ijms-20-04809-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/761c/6801368/391f9a020b0e/ijms-20-04809-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/761c/6801368/be3795c681dd/ijms-20-04809-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/761c/6801368/5ec2ae75fde3/ijms-20-04809-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/761c/6801368/391f9a020b0e/ijms-20-04809-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/761c/6801368/be3795c681dd/ijms-20-04809-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/761c/6801368/5ec2ae75fde3/ijms-20-04809-g003.jpg

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本文引用的文献

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Identification of multiple male reproductive tract-specific proteins that regulate sperm migration through the oviduct in mice.鉴定多种调控精子在小鼠输卵管中迁移的雄性生殖管道特异性蛋白。
Proc Natl Acad Sci U S A. 2019 Sep 10;116(37):18498-18506. doi: 10.1073/pnas.1908736116. Epub 2019 Aug 27.
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An update of the regulatory factors of sperm migration from the uterus into the oviduct by genetically manipulated mice.通过基因改造小鼠更新调控精子从子宫迁移到输卵管的因素。
Mol Reprod Dev. 2019 Aug;86(8):935-955. doi: 10.1002/mrd.23180. Epub 2019 May 27.
3
Alternative splicing of the Izumo1 gene ensures triggering gamete fusion in mice.
C11orf94/Frey通过控制Izumo1复合物组装,是男性生育力的关键调节因子。
Sci Adv. 2022 Aug 12;8(32):eabo6049. doi: 10.1126/sciadv.abo6049.
4
The Role of Sperm Proteins IZUMO1 and TMEM95 in Mammalian Fertilization: A Systematic Review.精子蛋白 IZUMO1 和 TMEM95 在哺乳动物受精中的作用:系统评价。
Int J Mol Sci. 2022 Apr 1;23(7):3929. doi: 10.3390/ijms23073929.
5
Cell Fusion-Related Proteins and Signaling Pathways, and Their Roles in the Development and Progression of Cancer.细胞融合相关蛋白与信号通路及其在癌症发生发展中的作用
Front Cell Dev Biol. 2022 Feb 1;9:809668. doi: 10.3389/fcell.2021.809668. eCollection 2021.
Izumo1 基因的可变剪接确保了小鼠配子融合的触发。
Sci Rep. 2019 Feb 28;9(1):3151. doi: 10.1038/s41598-019-40130-7.
4
Monitoring dimeric status of IZUMO1 during the acrosome reaction in living spermatozoon.监测活体精子顶体反应过程中 IZUMO1 的二聚体状态。
Cell Cycle. 2018;17(11):1279-1285. doi: 10.1080/15384101.2018.1489181. Epub 2018 Jul 25.
5
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Reprod Med Biol. 2017 Mar 20;16(2):89-98. doi: 10.1002/rmb2.12021. eCollection 2017 Apr.
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Changes of IZUMO1 in bull spermatozoa during the maturation, acrosome reaction, and cryopreservation.在成熟、顶体反应和冷冻保存过程中公牛精子中IZUMO1的变化。
Theriogenology. 2016 Dec;86(9):2179-2188.e3. doi: 10.1016/j.theriogenology.2016.07.010. Epub 2016 Jul 21.
7
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