Oviduct extracellular vesicles protein content and their role during oviduct-embryo cross-talk

Oviduct extracellular vesicles protein content and their role during oviduct-embryo cross-talk
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DOI:
10.1530/rep-17-0054
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发表时间:
2017-09-01
期刊:
影响因子:
3.8
通讯作者:
Mermillod, Pascal
Mermillod, Pascal
中科院分区:
生物学3区
文献类型:
--
作者:
Alminana, Carmen;Corbin, Emilie;Mermillod, Pascal

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成功的怀孕需要母亲和胚胎之间进行适当的沟通。最近,输卵管液中存在的两种膜结合的细胞外小泡(EV)--外切体和微囊--被认为是这种独特的串扰的关键调节器。然而,对它们的含量及其在输卵管-胚胎对话中的作用知之甚少。鉴于体内和体外输卵管上皮细胞(OEC)分泌的已知差异,我们的目标是破译来自这两个来源的输卵管EVS蛋白含量。此外,我们还分析了它们对胚胎发育的功能影响。我们的研究首次证明了体内和体外输卵管EVS分泌/含量的显著差异。质谱分析鉴定了EVS中的319个蛋白质,其中186个蛋白质在体内和体外EVS的比较中差异表达(P<0.01)。有趣的是,97个仅在体内EV中表达,47个仅在体外表达,175个普遍存在。功能分析揭示了参与精子-卵母细胞结合、受精和胚胎发育的关键蛋白质,其中一些蛋白质在体外缺乏EVS。此外,我们还表明,体外产生的胚胎在培养过程中能够内化体内的EVS,在胚胎发育中具有功能效应。在体内,EVS可提高囊胚率,延长胚胎存活时间,提高胚胎质量。我们的研究首次提供了输卵管EVS的特征,增加了我们对输卵管EVS作为配子/胚胎-输卵管相互作用调节器的作用的理解。此外,我们的结果表明,它们是在体外条件下改善胚胎发育和存活的有前景的工具。
Successful pregnancy requires an appropriate communication between the mother and the embryo. Recently, exosomes and microvesicles, both membrane-bound extracellular vesicles (EVs) present in the oviduct fluid have been proposed as key modulators of this unique cross-talk. However, little is known about their content and their role during oviduct-embryo dialog. Given the known differences in secretions by in vivo and in vitro oviduct epithelial cells (OEC), we aimed at deciphering the oviduct EVs protein content from both sources. Moreover, we analyzed their functional effect on embryo development. Our study demonstrated for the first time the substantial differences between in vivo and in vitro oviduct EVs secretion/content. Mass spectrometry analysis identified 319 proteins in EVs, from which 186 were differentially expressed when in vivo and in vitro EVs were compared (P < 0.01). Interestingly, 97 were exclusively expressed in in vivo EVs, 47 were present only in in vitro and 175 were common. Functional analysis revealed key proteins involved in sperm-oocyte binding, fertilization and embryo development, some of them lacking in in vitro EVs. Moreover, we showed that in vitro-produced embryos were able to internalize in vivo EVs during culture with a functional effect in the embryo development. In vivo EVs increased blastocyst rate, extended embryo survival over time and improved embryo quality. Our study provides the first characterization of oviduct EVs, increasing our understanding of the role of oviduct EVs as modulators of gamete/embryo-oviduct interactions. Moreover, our results point them as promising tools to improve embryo development and survival under in vitro conditions.