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      Insights Into Extracellular Vesicle/Exosome and miRNA Mediated Bi-Directional Communication During Porcine Pregnancy

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          Abstract

          Spontaneous fetal loss is one of the most important challenges that commercial pig industry is still facing in North America. Research over the decade provided significant insights into some of the associated mechanisms including uterine capacity, placental efficiency, deficits in vasculature, and immune-inflammatory alterations at the maternal-fetal interface. Pigs have unique epitheliochorial placentation where maternal and fetal layers lay in opposition without any invasion. This has provided researchers opportunities to accurately tease out some of the mechanisms associated with maternal-fetal interface adaptations to the constantly evolving needs of a developing conceptus. Another unique feature of porcine pregnancy is the conceptus derived recruitment of immune cells during the window of conceptus attachment. These immune cells in turn participate in pregnancy associated vascular changes and contribute toward tolerance to the semi-allogeneic fetus. However, the precise mechanism of how maternal-fetal cells communicate during the critical times in gestation is not fully understood. Recently, it has been established that bi-directional communication between fetal trophoblasts and maternal cells/tissues is mediated by extracellular vesicles (EVs) including exosomes. These EVs are detected in a variety of tissues and body fluids and their role has been described in modulating several physiological and pathological processes including vascularization, immune-modulation, and homeostasis. Recent literature also suggests that these EVs (exosomes) carry cargo (nucleic acids, protein, and lipids) as unique signatures associated with some of the pregnancy associated pathologies. In this review, we provide overview of important mechanisms in porcine pregnancy success and failure and summarize current knowledge about the unique cargo containing biomolecules in EVs. We also discuss how EVs (including exosomes) transfer their contents into other cells and regulate important biological pathways critical for pregnancy success.

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          Most cited references152

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          Shedding light on the cell biology of extracellular vesicles

          Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising exosomes and microvesicles, which originate from the endosomal system or which are shed from the plasma membrane, respectively. They are present in biological fluids and are involved in multiple physiological and pathological processes. Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material. Knowledge of the cellular processes that govern extracellular vesicle biology is essential to shed light on the physiological and pathological functions of these vesicles as well as on clinical applications involving their use and/or analysis. However, in this expanding field, much remains unknown regarding the origin, biogenesis, secretion, targeting and fate of these vesicles.
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            Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.

            Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).
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              Biological properties of extracellular vesicles and their physiological functions

              In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.
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                Author and article information

                Contributors
                Journal
                Front Vet Sci
                Front Vet Sci
                Front. Vet. Sci.
                Frontiers in Veterinary Science
                Frontiers Media S.A.
                2297-1769
                15 April 2021
                2021
                : 8
                : 654064
                Affiliations
                [1] 1Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University , Baton Rouge, LA, United States
                [2] 2Department Biomedical and Molecular Sciences, Queen's University , Kingston, ON, Canada
                [3] 3Department of Obstetrics and Gynecology, Queen's University , Kingston, ON, Canada
                Author notes

                Edited by: Dariusz Jan Skarzynski, Institute of Animal Reproduction and Food Research (PAS), Poland

                Reviewed by: Aneta Andronowska, Institute of Animal Reproduction and Food Research (PAS), Poland; Hakhyun Ka, Yonsei University, South Korea

                *Correspondence: Chandrakant Tayade tayadec@ 123456queensu.ca

                This article was submitted to Animal Reproduction - Theriogenology, a section of the journal Frontiers in Veterinary Science

                Article
                10.3389/fvets.2021.654064
                8081834
                33937376
                c8b0fc22-4c49-4ef8-97c2-87f89b28a3f5
                Copyright © 2021 Bidarimath, Lingegowda, Miller, Koti and Tayade.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 January 2021
                : 11 March 2021
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 153, Pages: 13, Words: 11711
                Funding
                Funded by: Natural Sciences and Engineering Research Council of Canada 10.13039/501100000038
                Categories
                Veterinary Science
                Review

                angiogenesis,cytokines,exosomes,fetal loss,immune cells,inflammation,trophoblasts

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