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      Extracellular vesicles and reproduction–promotion of successful pregnancy

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          Abstract

          Extracellular vesicles (EVs) are membrane-bound complexes secreted from cells under both physiological and pathological conditions. They contain proteins, nucleic acids and lipids and act as messengers for cell–cell communication and signalling, particularly between immune cells. EV research is a rapidly evolving and expanding field, and it appears that all biological fluids contain very large numbers of EVs; they are produced from all cells that have been studied to date, and are known to have roles in several reproductive processes. This review analyses the evidence for the role of EVs throughout human reproduction, starting with the paternal and maternal gametes, followed by the establishment and continuation of successful pregnancies, with specific focus, where possible, on the interaction of EVs with the maternal immune system. Importantly, variations within the EV populations are identified in various reproductive disorders, such as pre-term labour and pre-eclampsia.

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          Characterization of microRNA expression profiles in normal human tissues

          Hao-Yu Liang, Dana Ridzon, Linda Wong … (2007)
          Background Measuring the quantity of miRNAs in tissues of different physiological and pathological conditions is an important first step to investigate the functions of miRNAs. Matched samples from normal state can provide essential baseline references to analyze the variation of miRNA abundance. Results We provided expression data of 345 miRNAs in 40 normal human tissues, which identified universally expressed miRNAs, and several groups of miRNAs expressed exclusively or preferentially in certain tissue types. Many miRNAs with co-regulated expression patterns are located within the same genomic clusters, and candidate transcriptional factors that control the pattern of their expression may be identified by a comparative genomic strategy. Hierarchical clustering of normal tissues by their miRNA expression profiles basically followed the structure, anatomical locations, and physiological functions of the organs, suggesting that functions of a miRNA could be appreciated by linking to the biologies of the tissues in which it is uniquely expressed. Many predicted target genes of miRNAs that had specific reduced expression in brain and peripheral blood mononuclear cells are required for embryonic development of the nervous and hematopoietic systems based on database search. Conclusion We presented a global view of tissue distribution of miRNAs in relation to their chromosomal locations and genomic structures. We also described evidence from the cis-regulatory elements and the predicted target genes of miRNAs to support their tissue-specific functional roles to regulate the physiologies of the normal tissues in which they are expressed.
          Article 0 comments Cited 355 times – based on 0 reviews     Review now
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            Human villous trophoblasts express and secrete placenta-specific microRNAs into maternal circulation via exosomes.

            Shan-Shun Luo, Osamu Ishibashi, Gen Ishikawa … (2009)
            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.
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              Human placental trophoblasts confer viral resistance to recipient cells.

              E. Delorme-Axford, R Donker, J-F Mouillet … (2013)
              Placental trophoblasts form the interface between the fetal and maternal environments and serve to limit the maternal-fetal spread of viruses. Here we show that cultured primary human placental trophoblasts are highly resistant to infection by a number of viruses and, importantly, confer this resistance to nonplacental recipient cells by exosome-mediated delivery of specific microRNAs (miRNAs). We show that miRNA members of the chromosome 19 miRNA cluster, which are almost exclusively expressed in the human placenta, are packaged within trophoblast-derived exosomes and attenuate viral replication in recipient cells by the induction of autophagy. Together, our findings identify an unprecedented paracrine and/or systemic function of placental trophoblasts that uses exosome-mediated transfer of a unique set of placental-specific effector miRNAs to directly communicate with placental or maternal target cells and regulate their immunity to viral infections.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cell Mol Immunol
                Journal ID (iso-abbrev): Cell. Mol. Immunol
                Title: Cellular and Molecular Immunology
                Publisher: Nature Publishing Group
                ISSN (Print): 1672-7681
                ISSN (Electronic): 2042-0226
                Publication date (Print): November 2014
                Publication date (Electronic): 23 June 2014
                Publication date PMC-release: 1 November 2014
                Volume: 11
                Issue: 6
                Pages: 548-563
                Affiliations
                [1]Nuffield Department of Obstetrics and Gynaecology, University of Oxford John Radcliffe Hospital Oxford , UK
                Author notes
                [* ]Nuffield Department of Obstetrics and Gynaecology, University of Oxford John Radcliffe Hospital Oxford , OX3 9DU, UK. E-mail: dionne.tannetta@ 123456obs-gyn.ox.ac.uk
                Article
                Publisher Item ID: cmi201442
                DOI: 10.1038/cmi.2014.42
                PMC ID: 4220835
                PubMed ID: 24954226
                SO-VID: f2b1be93-c38e-454b-8efb-71fa1a10038d
                Copyright © Copyright © 2014 Chinese Society of Immunology and The University of Science and Technology
                License:

                This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0

                History
                Date received : 09 May 2014
                Date accepted : 11 May 2014
                Categories
                Subject: Review

                ScienceOpen disciplines: Immunology
                Keywords: extracellular vesicles,pregnancy,microvesicles,exosomes,nanoparticle tracking analysis,pre-eclampsia
                Data availability:
                ScienceOpen disciplines: Immunology
                Keywords: extracellular vesicles, pregnancy, microvesicles, exosomes, nanoparticle tracking analysis, pre-eclampsia

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