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期刊名称: Biology of Reproduction
Volume:81    Issue:4        Page:717-729
ISSN:0006-3363

Human Villous Trophoblasts Express and Secrete Placenta-Specific MicroRNAs into Maternal Circulation via Exosomes期刊论文

作者: Shan-Shun Luo Osamu Ishibashi Gen Ishikawa Tomoko Ishikawa Akira Katayama
DOI:10.1095/biolreprod.108.075481

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页码: 717-729
被引频次: 241
出版者: Society for the Study of Reproduction,SOC STUDY REPRODUCTION
期刊名称: Biology of Reproduction
ISSN: 0006-3363
卷期: Volume:81    Issue:4
语言: English
摘要: In this study, we performed small RNA library sequencing using human placental tissues to identify placenta-specific miRNAs. We also tested the hypothesis that human chorionic villi could secrete miRNAs extracellularly via exosomes, which in turn enter into maternal circulation. By small RNA library sequencing, most placenta-specific miRNAs (e.g., MIR517A ) were linked to a miRNA cluster on chromosome 19. The miRNA cluster genes were differentially expressed in placental development. Subsequent validation by real-time PCR and in situ hybridization revealed that villous trophoblasts express placenta-specific miRNAs. The analysis of small RNA libraries from the blood plasma showed that the placenta-specific miRNAs are abundant in the plasma of pregnant women. By real-time PCR, we confirmed the rapid clearance of the placenta-specific miRNAs from the plasma after delivery, indicating that such miRNAs enter into maternal circulation. By using the trophoblast cell line BeWo in culture, we demonstrated that miRNAs are indeed extracellularly released via exosomes. Taken together, our findings suggest that miRNAs are exported from the human placental syncytiotrophoblast into maternal circulation, where they could target maternal tissues. Finally, to address the biological functions of placenta-specific miRNAs, we performed a proteome analysis of BeWo cells transfected with MIR517A . Bioinformatic analysis suggests that this miRNA is possibly involved in tumor necrosis factor-mediated signaling. Our data provide important insights into miRNA biology of the human placenta.
相关主题: Human placenta, Pregnancy, Placenta, Exosome, Tumor necrosis factor, Maternal blood plasma, MiRNA, Syncytiotrophoblast, Trophoblast, CELLS, SMALL RNAS, maternal blood plasma, pregnancy, MOUSE, ANIMAL DEVELOPMENT, IDENTIFICATION, CANCER, BIOMARKERS, REPRODUCTIVE BIOLOGY, CAENORHABDITIS-ELEGANS, tumor necrosis factor, REPRESSION, human placenta, miRNA, placenta, trophoblast, exosome, syncytiotrophoblast, EMBRYOS, Cell Line, Trophoblasts - metabolism, Humans, MicroRNAs - metabolism, Gene Expression Profiling, Chorionic Villi - metabolism, Chorionic Villi - secretion, MicroRNAs - secretion, In Situ Hybridization, Sequence Analysis, RNA, Trophoblasts - secretion, Polymerase Chain Reaction, Proteomics, Female, Pregnancy - blood, Exosomes - secretion, Index Medicus,

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