Shi Shuang, Tan Qiang, Liang Jingjie, Cao Dingren, Wang Shaoyu, Liang Junyong, Chen Kaiyu, Wang Zhengguang
College of Animal Science, Zhejiang University, Hangzhou 310058, PR China.
Hainan Institute, Zhejiang University, Sanya 572000, PR China.
Mol Ther Nucleic Acids. 2021 Sep 24;26:760-772. doi: 10.1016/j.omtn.2021.09.009. eCollection 2021 Dec 3.
Communication between the maternal uterus and the embryo is vital for a successful pregnancy. Exosomes, subtypes of extracellular vesicles comprising many bioactive factors, regulate the early stages of pregnancy, specifically during embryo implantation. Nevertheless, the mechanism by which exosomal microRNAs (miRNAs) derived from placental trophoblasts regulate embryo implantation remains elusive. We isolated and identified exosomes derived from placental trophoblast cells (HTR8/SVneo). Subsequently, we evaluated the loading miRNA in exosomes by small RNA sequencing. Consequently, we showed that trophoblast cell-derived exosomes could transfer to endometrial epithelial cells. Besides, these exosomes promoted the epithelial-mesenchymal transition (EMT) as well as migration of endometrial cells and were implicated in the regulation of inflammation. Further, the specific miRNAs were screened in exosomes, and as a result, miRNA (miR)-1290 was enriched specifically in exosomes. miR-1290 promoted the expression of inflammatory factors (interleukin [IL]-6 and IL-8) and migration of endometrial epithelial cells. In addition, exosomal miR-1290 promoted angiogenesis . More importantly, by targeting LHX6, trophoblast HTR8/SVneo cell-derived exosomal miR-1290 promoted the EMT process of endometrial epithelial cell HEC-1-A. Altogether, our findings provide novel insights into the mechanism of trophoblast cell-derived exosomes during embryo implantation.
母体子宫与胚胎之间的通讯对于成功怀孕至关重要。外泌体是包含许多生物活性因子的细胞外囊泡亚型,可调节妊娠早期,特别是在胚胎着床期间。然而,源自胎盘滋养层细胞的外泌体微小RNA(miRNA)调节胚胎着床的机制仍不清楚。我们分离并鉴定了源自胎盘滋养层细胞(HTR8/SVneo)的外泌体。随后,我们通过小RNA测序评估了外泌体中装载的miRNA。结果表明,滋养层细胞来源的外泌体可以转移到子宫内膜上皮细胞。此外,这些外泌体促进了上皮-间质转化(EMT)以及子宫内膜细胞的迁移,并参与了炎症调节。此外,我们在外泌体中筛选出了特定的miRNA,结果发现,miRNA(miR)-1290在外泌体中特异性富集。miR-1290促进了炎症因子(白细胞介素[IL]-6和IL-8)的表达以及子宫内膜上皮细胞的迁移。此外,外泌体miR-1290促进了血管生成。更重要的是,通过靶向LHX6,滋养层HTR8/SVneo细胞来源的外泌体miR-1290促进了子宫内膜上皮细胞HEC-1-A的EMT过程。总之,我们的研究结果为胚胎着床期间滋养层细胞来源的外泌体机制提供了新的见解。