Endometrial exosomes/microvesicles in the uterine microenvironment: a new paradigm for embryo-endometrial cross talk at implantation.
Endometrial exosomes/microvesicles in the uterine microenvironment: a new paradigm for embryo-endometrial cross talk at implantation.
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DOI：
10.1371/journal.pone.0058502
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Salamonsen LA
中科院分区：
文献类型：
--
作者：
Ng YH;Rome S;Jalabert A;Forterre A;Singh H;Hincks CL;Salamonsen LA
外泌体是从细胞中释放的纳米颗粒（直径约100 nm），它可以通过细胞外环境将小rna和mRNA转移到远处的细胞中。我们假设外泌体或稍大的微泡（100-300 nm）从子宫内膜上皮释放到子宫腔，这些微泡含有特定的微（mi）RNA，可以转移到囊胚的滋养外胚层细胞或子宫内膜上皮细胞，以促进着床。本研究的目的是专门鉴定和表征子宫内膜上皮细胞释放的外泌体/微囊泡（mv），并确定外泌体/微囊泡是否存在于子宫液中。免疫染色显示，在月经周期的组织切片中，作为外泌体细胞表面标记物的tetraspanins、CD9和CD63存在于子宫内膜上皮细胞的顶端表面：CD63表现出周期性调节。以子宫内膜上皮细胞（ECC1细胞）和子宫液及其相关黏液为培养基，采用连续超离心培养法制备外泌体/mv微球。外泌体与微球结合后，通过FACS和免疫荧光染色在所有制剂中阳性鉴定出外泌体/mv。粒径颗粒分析证实了每种流体中50 - 150nm颗粒的优势。对ECC1细胞及其外泌体/mv的MiRNA分析表明，MiRNA可以分选到外泌体/mv中：227个MiRNA中有13个特异于外泌体/mv，另外5个不存在于外泌体/mv中。外泌体/mv中最丰富的miRNA是hsa-miR-200c、hsa-miR-17和hsa-miR-106a。生物信息学分析表明，外泌体/mv特异性mirna在与胚胎着床高度相关的生物学途径中具有潜在的靶点。因此，含有特定miRNA的外泌体/mv存在于胚胎着床发生的微环境中，并可能促成这一过程所必需的子宫内膜-胚胎串扰。
Exosomes are nanoparticles (∼100 nm diameter) released from cells, which can transfer small RNAs and mRNA via the extracellular environment to cells at distant sites. We hypothesised that exosomes or the slightly larger microvesicles (100–300 nm) are released from the endometrial epithelium into the uterine cavity, and that these contain specific micro (mi)RNA that could be transferred to either the trophectodermal cells of the blastocyst or to endometrial epithelial cells, to promote implantation. The aim of this study was to specifically identify and characterise exosomes/microvesicles (mv) released from endometrial epithelial cells and to determine whether exosomes/mv are present in uterine fluid. Immunostaining demonstrated that the tetraspanins, CD9 and CD63 used as cell surface markers of exosomes are present on the apical surfaces of endometrial epithelial cells in tissue sections taken across the menstrual cycle: CD63 showed cyclical regulation. Exosome/mv pellets were prepared from culture medium of endometrial epithelial cell (ECC1 cells) and from uterine fluid and its associated mucus by sequential ultracentifugation. Exosomes/mv were positively identified in all preparations by FACS and immunofluorescence staining following exosome binding to beads. Size particle analysis confirmed the predominance of particles of 50–150 nm in each of these fluids. MiRNA analysis of the ECC1 cells and their exosomes/mv demonstrated sorting of miRNA into exosomes/mv: 13 of the 227 miRNA were specific to exosomes/mv, while a further 5 were not present in these. The most abundant miRNA in exosomes/mv were hsa-miR-200c, hsa-miR-17 and hsa-miR-106a. Bioinformatic analysis showed that the exosome/mv-specific miRNAs have potential targets in biological pathways highly relevant for embryo implantation. Thus exosomes/mv containing specific miRNA are present in the microenvironment in which embryo implantation occurs and may contribute to the endometrial-embryo cross talk essential for this process.
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