Oxygen tension regulates the miRNA profile and bioactivity of exosomes released from extravillous trophoblast cells - Liquid biopsies for monitoring complications of pregnancy
Our understanding of how cells communicate has undergone a paradigm shift since the recent recognition of the role of exosomes in intercellular signaling. In this study, we investigated whether oxygen tension alters the exosome release and miRNA profile from extravillous trophoblast (EVT) cells, mod...
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| Veröffentlicht in: | PloS one 2017-03, Vol.12 (3), p.e0174514-e0174514 |
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| creator | Truong, Grace Guanzon, Dominic Kinhal, Vyjayanthi Elfeky, Omar Lai, Andrew Longo, Sherri Nuzhat, Zarin Palma, Carlos Scholz-Romero, Katherin Menon, Ramkumar Mol, Ben W Rice, Gregory E Salomon, Carlos |
| description | Our understanding of how cells communicate has undergone a paradigm shift since the recent recognition of the role of exosomes in intercellular signaling. In this study, we investigated whether oxygen tension alters the exosome release and miRNA profile from extravillous trophoblast (EVT) cells, modifying their bioactivity on endothelial cells (EC). Furthermore, we have established the exosomal miRNA profile at early gestation in women who develop pre-eclampsia (PE) and spontaneous preterm birth (SPTB). HTR-8/SVneo cells were used as an EVT model. The effect of oxygen tension (i.e. 8% and 1% oxygen) on exosome release was quantified using nanocrystals (Qdot®) coupled to CD63 by fluorescence NTA. A real-time, live-cell imaging system (Incucyte™) was used to establish the effect of exosomes on EC. Plasma samples were obtained at early gestation ( |
| doi_str_mv | 10.1371/journal.pone.0174514 |
| format | Article |
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In this study, we investigated whether oxygen tension alters the exosome release and miRNA profile from extravillous trophoblast (EVT) cells, modifying their bioactivity on endothelial cells (EC). Furthermore, we have established the exosomal miRNA profile at early gestation in women who develop pre-eclampsia (PE) and spontaneous preterm birth (SPTB). HTR-8/SVneo cells were used as an EVT model. The effect of oxygen tension (i.e. 8% and 1% oxygen) on exosome release was quantified using nanocrystals (Qdot®) coupled to CD63 by fluorescence NTA. A real-time, live-cell imaging system (Incucyte™) was used to establish the effect of exosomes on EC. Plasma samples were obtained at early gestation (<18 weeks) and classified according to pregnancy outcomes. An Illumina TrueSeq Small RNA kit was used to construct a small RNA library from exosomal RNA obtained from EVT and plasma samples. The number of exosomes was significantly higher in EVT cultured under 1% compared to 8% oxygen. In total, 741 miRNA were identified in exosomes from EVT. Bioinformatic analysis revealed that these miRNA were associated with cell migration and cytokine production. Interestingly, exosomes isolated from EVT cultured at 8% oxygen increased EC migration, whilst exosomes cultured at 1% oxygen decreased EC migration. These changes were inversely proportional to TNF-α released from EC. Finally, we have identified a set of unique miRNAs in exosomes from EVT cultured at 1% oxygen and exosomes isolated from the circulation of mothers at early gestation, who later developed PE and SPTB. We suggest that aberrant exosomal signalling by placental cells is a common aetiological factor in pregnancy complications characterised by incomplete SpA remodeling and is therefore a clinically relevant biomarker of pregnancy complications.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0174514</identifier><identifier>PMID: 28350871</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Angiogenesis ; Apoptosis ; Arteries - metabolism ; Biochemistry ; Biological activity ; Biology ; Biology and Life Sciences ; Biopsy - methods ; Blotting, Western ; Breast cancer ; Causes of ; CD63 antigen ; Cell migration ; Cell Movement - genetics ; Cells, Cultured ; Chorionic Villi - metabolism ; Cluster Analysis ; Crystals ; Endothelial cells ; Exosomes ; Exosomes - genetics ; Exosomes - metabolism ; Exosomes - ultrastructure ; Female ; Gene Expression Profiling - methods ; Gestation ; Gynecology ; Health aspects ; Human Umbilical Vein Endothelial Cells - cytology ; Human Umbilical Vein Endothelial Cells - metabolism ; Humans ; Hypoxia ; Immunology ; Laboratories ; Liver cancer ; Medicine ; Medicine and Health Sciences ; MicroRNA ; MicroRNAs ; MicroRNAs - blood ; MicroRNAs - genetics ; Microscopy, Electron, Transmission ; miRNA ; Nanocrystals ; Obstetrics ; Oxygen ; Oxygen - metabolism ; Oxygen - pharmacology ; Oxygen tension ; Oxygen therapy ; Pharmacy ; Physical Sciences ; Placenta ; Pre-eclampsia ; Preeclampsia ; Pregnancy ; Pregnancy complications ; Pregnancy Complications - blood ; Pregnancy Complications - genetics ; Pregnancy Complications - metabolism ; Pregnant women ; Premature birth ; Resorts & spas ; Ribonucleic acid ; Risk factors ; RNA ; Smooth muscle ; Trophoblasts - cytology ; Trophoblasts - drug effects ; Trophoblasts - metabolism ; Tumorigenesis ; Uterine diseases ; Uterus - blood supply ; Veins & arteries ; Womens health</subject><ispartof>PloS one, 2017-03, Vol.12 (3), p.e0174514-e0174514</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Truong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Truong et al 2017 Truong et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c809t-6780684e3134f74e8aaa44c31b3c59b8b0265d24ec9ce553b83c9d6f9e5099e33</citedby><cites>FETCH-LOGICAL-c809t-6780684e3134f74e8aaa44c31b3c59b8b0265d24ec9ce553b83c9d6f9e5099e33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370130/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370130/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28350871$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Truong, Grace</creatorcontrib><creatorcontrib>Guanzon, Dominic</creatorcontrib><creatorcontrib>Kinhal, Vyjayanthi</creatorcontrib><creatorcontrib>Elfeky, Omar</creatorcontrib><creatorcontrib>Lai, Andrew</creatorcontrib><creatorcontrib>Longo, Sherri</creatorcontrib><creatorcontrib>Nuzhat, Zarin</creatorcontrib><creatorcontrib>Palma, Carlos</creatorcontrib><creatorcontrib>Scholz-Romero, Katherin</creatorcontrib><creatorcontrib>Menon, Ramkumar</creatorcontrib><creatorcontrib>Mol, Ben W</creatorcontrib><creatorcontrib>Rice, Gregory E</creatorcontrib><creatorcontrib>Salomon, Carlos</creatorcontrib><title>Oxygen tension regulates the miRNA profile and bioactivity of exosomes released from extravillous trophoblast cells - Liquid biopsies for monitoring complications of pregnancy</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Our understanding of how cells communicate has undergone a paradigm shift since the recent recognition of the role of exosomes in intercellular signaling. In this study, we investigated whether oxygen tension alters the exosome release and miRNA profile from extravillous trophoblast (EVT) cells, modifying their bioactivity on endothelial cells (EC). Furthermore, we have established the exosomal miRNA profile at early gestation in women who develop pre-eclampsia (PE) and spontaneous preterm birth (SPTB). HTR-8/SVneo cells were used as an EVT model. The effect of oxygen tension (i.e. 8% and 1% oxygen) on exosome release was quantified using nanocrystals (Qdot®) coupled to CD63 by fluorescence NTA. A real-time, live-cell imaging system (Incucyte™) was used to establish the effect of exosomes on EC. Plasma samples were obtained at early gestation (<18 weeks) and classified according to pregnancy outcomes. An Illumina TrueSeq Small RNA kit was used to construct a small RNA library from exosomal RNA obtained from EVT and plasma samples. The number of exosomes was significantly higher in EVT cultured under 1% compared to 8% oxygen. In total, 741 miRNA were identified in exosomes from EVT. Bioinformatic analysis revealed that these miRNA were associated with cell migration and cytokine production. Interestingly, exosomes isolated from EVT cultured at 8% oxygen increased EC migration, whilst exosomes cultured at 1% oxygen decreased EC migration. These changes were inversely proportional to TNF-α released from EC. Finally, we have identified a set of unique miRNAs in exosomes from EVT cultured at 1% oxygen and exosomes isolated from the circulation of mothers at early gestation, who later developed PE and SPTB. We suggest that aberrant exosomal signalling by placental cells is a common aetiological factor in pregnancy complications characterised by incomplete SpA remodeling and is therefore a clinically relevant biomarker of pregnancy complications.</description><subject>Adult</subject><subject>Angiogenesis</subject><subject>Apoptosis</subject><subject>Arteries - metabolism</subject><subject>Biochemistry</subject><subject>Biological activity</subject><subject>Biology</subject><subject>Biology and Life Sciences</subject><subject>Biopsy - methods</subject><subject>Blotting, Western</subject><subject>Breast cancer</subject><subject>Causes of</subject><subject>CD63 antigen</subject><subject>Cell migration</subject><subject>Cell Movement - genetics</subject><subject>Cells, Cultured</subject><subject>Chorionic Villi - metabolism</subject><subject>Cluster Analysis</subject><subject>Crystals</subject><subject>Endothelial cells</subject><subject>Exosomes</subject><subject>Exosomes - genetics</subject><subject>Exosomes - metabolism</subject><subject>Exosomes - ultrastructure</subject><subject>Female</subject><subject>Gene Expression Profiling - methods</subject><subject>Gestation</subject><subject>Gynecology</subject><subject>Health aspects</subject><subject>Human Umbilical Vein Endothelial Cells - cytology</subject><subject>Human Umbilical Vein Endothelial Cells - metabolism</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Immunology</subject><subject>Laboratories</subject><subject>Liver cancer</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - blood</subject><subject>MicroRNAs - genetics</subject><subject>Microscopy, Electron, Transmission</subject><subject>miRNA</subject><subject>Nanocrystals</subject><subject>Obstetrics</subject><subject>Oxygen</subject><subject>Oxygen - metabolism</subject><subject>Oxygen - pharmacology</subject><subject>Oxygen tension</subject><subject>Oxygen therapy</subject><subject>Pharmacy</subject><subject>Physical Sciences</subject><subject>Placenta</subject><subject>Pre-eclampsia</subject><subject>Preeclampsia</subject><subject>Pregnancy</subject><subject>Pregnancy complications</subject><subject>Pregnancy Complications - blood</subject><subject>Pregnancy Complications - genetics</subject><subject>Pregnancy Complications - metabolism</subject><subject>Pregnant women</subject><subject>Premature birth</subject><subject>Resorts & spas</subject><subject>Ribonucleic acid</subject><subject>Risk factors</subject><subject>RNA</subject><subject>Smooth muscle</subject><subject>Trophoblasts - cytology</subject><subject>Trophoblasts - drug effects</subject><subject>Trophoblasts - metabolism</subject><subject>Tumorigenesis</subject><subject>Uterine diseases</subject><subject>Uterus - blood supply</subject><subject>Veins & arteries</subject><subject>Womens health</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9tq3DAQhk1padK0b1BaQaG0F7uVLNmWbwJL6CEQGkgPt0KWx14FWXIkOWSfqq9YebMJ2ZKLogsL-fv_GY1msuw1wUtCK_Lp0k3eSrMcnYUlJhUrCHuSHZKa5osyx_Tpg_1B9iKES4wLysvyeXaQc1pgXpHD7M_5zaYHiyLYoJ1FHvrJyAgBxTWgQV98X6HRu04bQNK2qNFOqqivddwg1yG4ccENifZgQAZoUefdkI6jl9faGDclI-_GtWuMDBEpMCagBTrTV5Peuo1BJ3nnPBqc1dF5bXuk3DAarWRMKYU5zpjystKqzcvsWSdNgFe771H268vnnyffFmfnX09PVmcLxXEdF2XFcckZUEJZVzHgUkrGFCUNVUXd8AbnZdHmDFStoChow6mq27KrocB1DZQeZW9vfUfjgtjVOgjCeZ6zquY4Eae3ROvkpRi9HqTfCCe12B443wvpo1YGBM9bSZoKJ9-WdS3ljFGsuqZouaprNkc73kWbmgFaBTbVz-yZ7v-xei16dy0KWmFC52Q-7Ay8u5ogRDHoMBdbWkhvsM0bc5yTKqHv_kEfv92O6mW6gLadS3HVbCpWjFcFxTkniVo-QqXVwqBVasy5b_YFH_cEiYmpWXo5hSBOf1z8P3v-e599_4BdgzRxHZyZtg20D7JbUHkXgofuvsgEi3mu7qoh5rkSu7lKsjcPH-hedDdI9C_wZyGc</recordid><startdate>20170328</startdate><enddate>20170328</enddate><creator>Truong, Grace</creator><creator>Guanzon, Dominic</creator><creator>Kinhal, Vyjayanthi</creator><creator>Elfeky, Omar</creator><creator>Lai, Andrew</creator><creator>Longo, Sherri</creator><creator>Nuzhat, Zarin</creator><creator>Palma, Carlos</creator><creator>Scholz-Romero, Katherin</creator><creator>Menon, Ramkumar</creator><creator>Mol, Ben W</creator><creator>Rice, Gregory E</creator><creator>Salomon, Carlos</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20170328</creationdate><title>Oxygen tension regulates the miRNA profile and bioactivity of exosomes released from extravillous trophoblast cells - Liquid biopsies for monitoring complications of pregnancy</title><author>Truong, Grace ; Guanzon, Dominic ; Kinhal, Vyjayanthi ; Elfeky, Omar ; Lai, Andrew ; Longo, Sherri ; Nuzhat, Zarin ; Palma, Carlos ; Scholz-Romero, Katherin ; Menon, Ramkumar ; Mol, Ben W ; Rice, Gregory E ; Salomon, Carlos</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c809t-6780684e3134f74e8aaa44c31b3c59b8b0265d24ec9ce553b83c9d6f9e5099e33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Angiogenesis</topic><topic>Apoptosis</topic><topic>Arteries - metabolism</topic><topic>Biochemistry</topic><topic>Biological activity</topic><topic>Biology</topic><topic>Biology and Life Sciences</topic><topic>Biopsy - methods</topic><topic>Blotting, Western</topic><topic>Breast cancer</topic><topic>Causes of</topic><topic>CD63 antigen</topic><topic>Cell migration</topic><topic>Cell Movement - genetics</topic><topic>Cells, Cultured</topic><topic>Chorionic Villi - metabolism</topic><topic>Cluster Analysis</topic><topic>Crystals</topic><topic>Endothelial cells</topic><topic>Exosomes</topic><topic>Exosomes - genetics</topic><topic>Exosomes - metabolism</topic><topic>Exosomes - ultrastructure</topic><topic>Female</topic><topic>Gene Expression Profiling - methods</topic><topic>Gestation</topic><topic>Gynecology</topic><topic>Health aspects</topic><topic>Human Umbilical Vein Endothelial Cells - cytology</topic><topic>Human Umbilical Vein Endothelial Cells - metabolism</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Immunology</topic><topic>Laboratories</topic><topic>Liver cancer</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - blood</topic><topic>MicroRNAs - genetics</topic><topic>Microscopy, Electron, Transmission</topic><topic>miRNA</topic><topic>Nanocrystals</topic><topic>Obstetrics</topic><topic>Oxygen</topic><topic>Oxygen - metabolism</topic><topic>Oxygen - pharmacology</topic><topic>Oxygen tension</topic><topic>Oxygen therapy</topic><topic>Pharmacy</topic><topic>Physical Sciences</topic><topic>Placenta</topic><topic>Pre-eclampsia</topic><topic>Preeclampsia</topic><topic>Pregnancy</topic><topic>Pregnancy complications</topic><topic>Pregnancy Complications - blood</topic><topic>Pregnancy Complications - genetics</topic><topic>Pregnancy Complications - metabolism</topic><topic>Pregnant women</topic><topic>Premature birth</topic><topic>Resorts & spas</topic><topic>Ribonucleic acid</topic><topic>Risk factors</topic><topic>RNA</topic><topic>Smooth muscle</topic><topic>Trophoblasts - cytology</topic><topic>Trophoblasts - drug effects</topic><topic>Trophoblasts - metabolism</topic><topic>Tumorigenesis</topic><topic>Uterine diseases</topic><topic>Uterus - blood supply</topic><topic>Veins & arteries</topic><topic>Womens health</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Truong, Grace</creatorcontrib><creatorcontrib>Guanzon, Dominic</creatorcontrib><creatorcontrib>Kinhal, Vyjayanthi</creatorcontrib><creatorcontrib>Elfeky, Omar</creatorcontrib><creatorcontrib>Lai, Andrew</creatorcontrib><creatorcontrib>Longo, Sherri</creatorcontrib><creatorcontrib>Nuzhat, Zarin</creatorcontrib><creatorcontrib>Palma, Carlos</creatorcontrib><creatorcontrib>Scholz-Romero, Katherin</creatorcontrib><creatorcontrib>Menon, Ramkumar</creatorcontrib><creatorcontrib>Mol, Ben W</creatorcontrib><creatorcontrib>Rice, Gregory E</creatorcontrib><creatorcontrib>Salomon, Carlos</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Truong, Grace</au><au>Guanzon, Dominic</au><au>Kinhal, Vyjayanthi</au><au>Elfeky, Omar</au><au>Lai, Andrew</au><au>Longo, Sherri</au><au>Nuzhat, Zarin</au><au>Palma, Carlos</au><au>Scholz-Romero, Katherin</au><au>Menon, Ramkumar</au><au>Mol, Ben W</au><au>Rice, Gregory E</au><au>Salomon, Carlos</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oxygen tension regulates the miRNA profile and bioactivity of exosomes released from extravillous trophoblast cells - Liquid biopsies for monitoring complications of pregnancy</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-03-28</date><risdate>2017</risdate><volume>12</volume><issue>3</issue><spage>e0174514</spage><epage>e0174514</epage><pages>e0174514-e0174514</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Our understanding of how cells communicate has undergone a paradigm shift since the recent recognition of the role of exosomes in intercellular signaling. In this study, we investigated whether oxygen tension alters the exosome release and miRNA profile from extravillous trophoblast (EVT) cells, modifying their bioactivity on endothelial cells (EC). Furthermore, we have established the exosomal miRNA profile at early gestation in women who develop pre-eclampsia (PE) and spontaneous preterm birth (SPTB). HTR-8/SVneo cells were used as an EVT model. The effect of oxygen tension (i.e. 8% and 1% oxygen) on exosome release was quantified using nanocrystals (Qdot®) coupled to CD63 by fluorescence NTA. A real-time, live-cell imaging system (Incucyte™) was used to establish the effect of exosomes on EC. Plasma samples were obtained at early gestation (<18 weeks) and classified according to pregnancy outcomes. An Illumina TrueSeq Small RNA kit was used to construct a small RNA library from exosomal RNA obtained from EVT and plasma samples. The number of exosomes was significantly higher in EVT cultured under 1% compared to 8% oxygen. In total, 741 miRNA were identified in exosomes from EVT. Bioinformatic analysis revealed that these miRNA were associated with cell migration and cytokine production. Interestingly, exosomes isolated from EVT cultured at 8% oxygen increased EC migration, whilst exosomes cultured at 1% oxygen decreased EC migration. These changes were inversely proportional to TNF-α released from EC. Finally, we have identified a set of unique miRNAs in exosomes from EVT cultured at 1% oxygen and exosomes isolated from the circulation of mothers at early gestation, who later developed PE and SPTB. We suggest that aberrant exosomal signalling by placental cells is a common aetiological factor in pregnancy complications characterised by incomplete SpA remodeling and is therefore a clinically relevant biomarker of pregnancy complications.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28350871</pmid><doi>10.1371/journal.pone.0174514</doi><tpages>e0174514</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2017-03, Vol.12 (3), p.e0174514-e0174514 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1882247980 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adult Angiogenesis Apoptosis Arteries - metabolism Biochemistry Biological activity Biology Biology and Life Sciences Biopsy - methods Blotting, Western Breast cancer Causes of CD63 antigen Cell migration Cell Movement - genetics Cells, Cultured Chorionic Villi - metabolism Cluster Analysis Crystals Endothelial cells Exosomes Exosomes - genetics Exosomes - metabolism Exosomes - ultrastructure Female Gene Expression Profiling - methods Gestation Gynecology Health aspects Human Umbilical Vein Endothelial Cells - cytology Human Umbilical Vein Endothelial Cells - metabolism Humans Hypoxia Immunology Laboratories Liver cancer Medicine Medicine and Health Sciences MicroRNA MicroRNAs MicroRNAs - blood MicroRNAs - genetics Microscopy, Electron, Transmission miRNA Nanocrystals Obstetrics Oxygen Oxygen - metabolism Oxygen - pharmacology Oxygen tension Oxygen therapy Pharmacy Physical Sciences Placenta Pre-eclampsia Preeclampsia Pregnancy Pregnancy complications Pregnancy Complications - blood Pregnancy Complications - genetics Pregnancy Complications - metabolism Pregnant women Premature birth Resorts & spas Ribonucleic acid Risk factors RNA Smooth muscle Trophoblasts - cytology Trophoblasts - drug effects Trophoblasts - metabolism Tumorigenesis Uterine diseases Uterus - blood supply Veins & arteries Womens health |
| title | Oxygen tension regulates the miRNA profile and bioactivity of exosomes released from extravillous trophoblast cells - Liquid biopsies for monitoring complications of pregnancy |
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