The effect of bta-miR-26b in intrauterine extracellular vesicles on maternal immune system during the implantation period
The effect of bta-miR-26b in intrauterine extracellular vesicles on maternal immune system during the implantation period
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DOI：
10.1016/j.bbrc.2021.08.019
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发表时间：
2021-08-14
影响因子：
3.1
通讯作者：
Imakawa, Kazuhiko
中科院分区：
文献类型：
--
作者：
Nakamura, Keigo;Kusama, Kazuya;Imakawa, Kazuhiko
子宫内的细胞外囊泡（EV）在围着床期孕子宫内膜（胚胎和胚外膜）之间的细胞相互作用中发挥作用。然而，子宫内EV如何对子宫内膜起作用尚未得到很好的表征。在我们之前的研究中，在妊娠第20天（最初的胚胎附着后半天，P20）的子宫冲洗液（UF）中发现的子宫内EV中的bta-miR-98可以调节母体免疫系统，并与其他miRNA和/或EV组分合作进行胚胎植入。因此，我们假设除了bta-miR-98，牛子宫内EV中存在的其他miRNA可能调节子宫内膜上皮中的母体免疫系统。对P17和P20 UFs EV之间差异表达蛋白的总体分析显示，宫内P20 EV的组分对“参与免疫应答的中性粒细胞活化”和“中性粒细胞介导的免疫”的下调具有影响。计算机模拟分析预测bta-miR-26 b是调节母体免疫系统的潜在miRNA之一。在我们的细胞培养实验中，bta-miR-26 b在牛子宫内膜上皮细胞中负调控几个免疫系统相关基因PSMC 6、CD 40和IER 3。我们的研究结果显示，子宫内EV衍生的bta-miR-26 b有助于母体免疫系统的下调，允许孕体植入子宫内膜。此外，我们的研究结果表明，从P20 UFs中提取的子宫内EV可以调节中性粒细胞，免疫防御的第一道防线，以调节子宫内膜的免疫和炎症反应，用于植入孕体。(c)2021爱思唯尔公司All rights reserved.
Extracellular vesicles (EVs) in utero play a role in cellular interactions between endometriumconceptuses (embryo plus extraembryonic membranes) during peri-implantation periods. However, how intrauterine EVs function on endometrium have not been well characterized. In our previous study, bta-miR-98 found in intrauterine EVs from uterine flushing fluids (UFs) on pregnant day 20 (a half day after initial conceptus attachment, P20) could regulate the maternal immune system and collaborate with other miRNAs and/or components of EVs for conceptus implantation. We, therefore, hypothesized that in addition to bta-miR-98, other miRNAs present in bovine intrauterine EVs may regulate the maternal immune system in the endometrial epithelium. A global analysis of differentially expressed proteins between EVs from P17 and P20 UFs revealed that components of intrauterine P20 EVs had the effect on the down-regulation of "neutrophil activation involved in immune response" and "neutrophil mediated immunity". In silico analyses predicted bta-miR-26b as one of potential miRNA to regulate maternal immune system. In our cell culture experiments, bta-miR-26b negatively regulated several immune system-related genes PSMC6, CD40, and IER3 in bovine endometrial epithelial cells. Our findings revealed that intrauterine EV-derived bta-miR-26b contributes to the down-regulation of the maternal immune system, allowing conceptus implantation to the uterine endometrium. Furthermore, our results suggest that intrauterine EVs extracted from P20 UFs could regulate neutrophils, the first line of immunological defense, to modulate endometrial immune and inflammatory responses for implanting conceptuses. (c) 2021 Elsevier Inc. All rights reserved.