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母龄对小鼠卵母细胞的影响:蛋白质组学分析带来的新生物学见解

Maternal age effect on mouse oocytes: new biological insight from proteomic analysis.

作者信息

Schwarzer Caroline, Siatkowski Marcin, Pfeiffer Martin J, Baeumer Nicole, Drexler Hannes C A, Wang Bingyuan, Fuellen Georg, Boiani Michele

机构信息

Max Planck Institute for Molecular BiomedicineRöntgenstraße 20, D-48149 Münster, GermanyDZNEGerman Centre for Neurodegenerative Disorders, Gehlsheimer Straße 20, D-18147 Rostock, GermanyInstitute for Biostatistics and Informatics in Medicine and Ageing ResearchRostock University Medical Center, Ernst Heydemann-Str. 8, D-18057 Rostock, GermanyArrows Biomedical GmbHGievenbecker Weg 11, D-48149 Münster, GermanyMax Planck Institute for Molecular BiomedicineBioanalytical Mass Spectrometry Facility, Röntgenstraße 20, D-48149 Münster, Germany.

Max Planck Institute for Molecular BiomedicineRöntgenstraße 20, D-48149 Münster, GermanyDZNEGerman Centre for Neurodegenerative Disorders, Gehlsheimer Straße 20, D-18147 Rostock, GermanyInstitute for Biostatistics and Informatics in Medicine and Ageing ResearchRostock University Medical Center, Ernst Heydemann-Str. 8, D-18057 Rostock, GermanyArrows Biomedical GmbHGievenbecker Weg 11, D-48149 Münster, GermanyMax Planck Institute for Molecular BiomedicineBioanalytical Mass Spectrometry Facility, Röntgenstraße 20, D-48149 Münster, GermanyMax Planck Institute for Molecular BiomedicineRöntgenstraße 20, D-48149 Münster, GermanyDZNEGerman Centre for Neurodegenerative Disorders, Gehlsheimer Straße 20, D-18147 Rostock, GermanyInstitute for Biostatistics and Informatics in Medicine and Ageing ResearchRostock University Medical Center, Ernst Heydemann-Str. 8, D-18057 Rostock, GermanyArrows Biomedical GmbHGievenbecker Weg 11, D-48149 Münster, GermanyMax Planck Institute for Molecular BiomedicineBioanalytical Mass Spectrometry Facility, Röntgenstraße 20, D-48149 Münster, Germany.

出版信息

Reproduction. 2014 Jul;148(1):55-72. doi: 10.1530/REP-14-0126. Epub 2014 Mar 31.

Abstract

The long-standing view of 'immortal germline vs mortal soma' poses a fundamental question in biology concerning how oocytes age in molecular terms. A mainstream hypothesis is that maternal ageing of oocytes has its roots in gene transcription. Investigating the proteins resulting from mRNA translation would reveal how far the levels of functionally available proteins correlate with mRNAs and would offer novel insights into the changes oocytes undergo during maternal ageing. Gene ontology (GO) semantic analysis revealed a high similarity of the detected proteome (2324 proteins) to the transcriptome (22 334 mRNAs), although not all proteins had a cognate mRNA. Concerning their dynamics, fourfold changes of abundance were more frequent in the proteome (3%) than the transcriptome (0.05%), with no correlation. Whereas proteins associated with the nucleus (e.g. structural maintenance of chromosomes and spindle-assembly checkpoints) were largely represented among those that change in oocytes during maternal ageing; proteins associated with oxidative stress/damage (e.g. superoxide dismutase) were infrequent. These quantitative alterations are either impoverishing or enriching. Using GO analysis, these alterations do not relate in any simple way to the classic signature of ageing known from somatic tissues. Given the lack of correlation, we conclude that proteome analysis of mouse oocytes may not be surrogated with transcriptome analysis. Furthermore, we conclude that the classic features of ageing may not be transposed from somatic tissues to oocytes in a one-to-one fashion. Overall, there is more to the maternal ageing of oocytes than mere cellular deterioration exemplified by the notorious increase of meiotic aneuploidy.

摘要

“不朽的生殖系与必死的体细胞”这一长期观点在生物学中提出了一个基本问题,即卵母细胞在分子层面是如何衰老的。一个主流假说是,卵母细胞的母体衰老源于基因转录。研究mRNA翻译产生的蛋白质将揭示功能可用蛋白质的水平与mRNA的相关程度,并为卵母细胞在母体衰老过程中所经历的变化提供新的见解。基因本体(GO)语义分析显示,检测到的蛋白质组(2324种蛋白质)与转录组(22334种mRNA)具有高度相似性,尽管并非所有蛋白质都有对应的mRNA。关于它们的动态变化,蛋白质组中丰度四倍变化比转录组(0.05%)更频繁(3%),且两者无相关性。在母体衰老过程中卵母细胞发生变化的蛋白质中,与细胞核相关的蛋白质(如染色体结构维持和纺锤体组装检查点)占很大比例;与氧化应激/损伤相关的蛋白质(如超氧化物歧化酶)则很少见。这些定量变化既有减少的也有增加的。通过GO分析,这些变化与从体细胞组织中已知的经典衰老特征没有任何简单的关联。鉴于缺乏相关性,我们得出结论,小鼠卵母细胞的蛋白质组分析不能用转录组分析来替代。此外,我们得出结论,衰老的经典特征可能不会以一对一的方式从体细胞组织转移到卵母细胞。总体而言,卵母细胞的母体衰老不仅仅是由减数分裂非整倍体显著增加所例证的单纯细胞退化。

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