Integral Proteomic Analysis of Blastocysts Reveals Key Molecular Machinery Governing Embryonic Diapause and Reactivation for Implantation in Mice

Integral Proteomic Analysis of Blastocysts Reveals Key Molecular Machinery Governing Embryonic Diapause and Reactivation for Implantation in Mice
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囊胚的整体蛋白质组学分析揭示了控制小鼠胚胎滞育和植入重新激活的关键分子机制

DOI:
10.1095/biolreprod.113.115337
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发表时间:
2014-03-01
影响因子:
3.6
通讯作者:
Wang, Haibin
Wang, Haibin
中科院分区:
生物学2区
文献类型:
--
作者:
Fu, Zheng;Wang, Bingyan;Wang, Haibin

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在近100种哺乳动物中,着床可以在囊胚阶段暂停一定时间,并在有利条件下重新激活,这种现象称为胚胎滞育。到目前为止,控制胚胎滞育和植入重新激活的潜在分子机制仍然很大程度上未知。在这里,我们使用生理相关的小鼠延迟着床模型对囊胚从滞育到重新激活的过程进行了首次整体蛋白质组学分析。超过 6000 个休眠和重新激活的囊胚被用于蛋白质组分析。总共检测到2255个蛋白质。各种细胞和分子过程,包括蛋白质翻译、有氧糖酵解、磷酸戊糖途径、嘌呤核苷酸生物合成、谷胱甘肽代谢和染色质组织被确定为差异调节的。特别是,我们证明了囊胚从休眠状态重新激活后线粒体的显着激活,突出了它们的重要生理意义。此外,在重新激活的囊胚的壁滋养外胚层中,内体-溶酶体系统的活性显着增强,并伴有胎儿-母体界面处的活跃吞噬作用,表明在促进滋养层侵袭中发挥着关键作用。总的来说,我们对滞育囊胚再激活的调控网络提供了完整的蛋白质组学观点,这将有助于更好地解释野生动物胚胎滞育和再激活的性质,并确定用于选择具有高植入能力的囊胚的分子指标。
Among nearly 100 mammalian species, implantation can be suspended at blastocyst stage for a certain time and reactivated under favorable conditions, a phenomenon known as embryonic diapause. Until now, the underlying molecular mechanism governing embryonic diapause and reactivation for implantation remained largely unknown. Here we conducted the first integral proteomic analysis of blastocysts from diapause to reactivation by using a physiologically relevant mouse delayed implantation model. More than 6000 dormant and reactivated blastocysts were used for the proteomic analysis. A total of 2255 proteins were detected. Various cellular and molecular processes, including protein translation, aerobic glycolysis, pentose phosphate pathway, purine nucleotide biosynthesis, glutathione metabolism, and chromatin organization were identified as differentially regulated. In particular, we demonstrated a remarkable activation of mitochondria in blastocysts upon reactivation from dormancy, highlighting their essential physiological significance. Moreover, the activities of the endosome-lysosome system were prominently enhanced in the mural trophectoderm of reactivated blastocysts, accompanied by active phagocytosis at the fetal-maternal interface, suggesting a critical role in promoting trophoblast invasion. Collectively, we provided an integral proteomic view upon the regulatory network of blastocyst reactivation from diapause, which will help to better interpret the nature of embryonic diapause and reactivation in wild animals and to identify molecular indicators for selecting blastocysts with high implantation competency.