{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:24:02Z","timestamp":1790115842171,"version":"4.0.1"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"vor","delay-in-days":220,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005047","name":"Natural Science Foundation of Liaoning Province","doi-asserted-by":"publisher","award":["2019-ZD-0769"],"award-info":[{"award-number":["2019-ZD-0769"]}],"id":[{"id":"10.13039\/501100005047","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>The placenta could transmit information to the maternal circulation via the secretion of small extracellular vesicles (sEVs), but little is known about whether and how these sEVs participate in premature labor (PTL). We speculate that miRNA plays an important role in sEV\u2010mediated fetal\u2010maternal information transmission. The present study was aimed at investigating whether the placenta can regulate the contraction of the maternal myometrium via sEV\u2010mediated transmit of miR\u201025\u20103p during PTL. The expression of miR\u201025\u20103p and its targets Cav3.2 and SERCA2a in clinical samples, cells, and animal specimens was detected. The role of miR\u201025\u20103p was observed in the LPS\u2010induced preterm labor mouse model. The sEVs from HTR\u20108\/SVneo cells were characterized by transmission electron microscopy and nanoparticle tracking analysis. The Ca<jats:sup>2+<\/jats:sup> oscillation in HMSMs was analyzed by an intracellular Ca<jats:sup>2+<\/jats:sup> change tracking assay on a confocal microscope. The contraction of HMSMs was detected by a collagen matrix contraction assay. We found that miR\u201025\u20103p can directly bind to the 3\u2009<jats:sup>\u2032<\/jats:sup>UTR of Cav3.2 and SERCA2a. The miR\u201025\u20103p level was decreased, and the expression of its targets Cav3.2 and SERCA2a was increased in the placenta and myometrium tissues of PTL patients. Forced upregulation of miR\u201025\u20103p reduced the oxidative stress and inflammation responses and the incidence of PTL in LPS\u2010treated mice. The expression of miR\u201025\u20103p was not changed in LPS\u2010stimulated human myometrial smooth muscle cells (HMSMs) but was strongly reduced in the trophoblast cell and its sEVs. Additionally, the trophoblast cell line HTR\u20108\/SVneo could transmit miR\u201025\u20103p into HMSMs via sEVs. The sEVs derived from LPS\u2010stimulated trophoblasts upregulated the expression of Cav3.2 and SERCA2a and triggered Ca<jats:sup>2+<\/jats:sup> oscillation as well as the contraction of HMSMs; these effects were partially reversed by the overexpression of miR\u201025\u20103p in the trophoblasts. Further, the upregulation of miR\u201025\u20103p induced changes of Ca<jats:sup>2+<\/jats:sup> oscillation and contraction of HMSMs mediated by sEVs which were also abrogated by the knockdown of miR\u201025\u20103p in HMSMs. The results demonstrated that miR\u201025\u20103p plays a crucial role in PTL via Cav3.2\u2010 and SERCA2a\u2010mediated Ca<jats:sup>2+<\/jats:sup> oscillation and contraction of HMSMs. PTL seems to be related to the decreased exosomal miR\u201025\u20103p content transmitted by the trophoblasts under inflammatory conditions.<\/jats:p>","DOI":"10.1155\/2021\/8140667","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:50:21Z","timestamp":1628556621000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Trophoblasts Modulate the Ca<sup>2+<\/sup> Oscillation and Contraction of Myometrial Smooth Muscle Cells by Small Extracellular Vesicle\u2010 (sEV\u2010) Mediated Exporting of miR\u201025\u20103p during Premature Labor"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9757-5542","authenticated-orcid":false,"given":"Lin","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7040-3268","authenticated-orcid":false,"given":"Wenzhu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7438-7197","authenticated-orcid":false,"given":"Ning","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1258-7614","authenticated-orcid":false,"given":"Lijuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,9]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2018.04.003"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60820-4"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.puhe.2014.03.010"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1590\/1518-8345.0775.2750"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200005183422007"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1121"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2017.00196"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2015.07.001"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-12-204"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.108.075481"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2018-00836"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13570"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2012-1199"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1071-5576(03)00089-3"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2014.07.003"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2009.02.010"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19051413"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1080\/01443615.2017.1331340"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.15503"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.4196\/kjpp.2009.13.3.241"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00225.2013"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsgi.2005.02.007"},{"key":"e_1_2_10_23_2","doi-asserted-by":"publisher","DOI":"10.1159\/000486912"},{"key":"e_1_2_10_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13073"},{"key":"e_1_2_10_25_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.69340"},{"key":"e_1_2_10_26_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201604-0814OC"},{"key":"e_1_2_10_27_2","doi-asserted-by":"publisher","DOI":"10.1177\/1933719118804420"},{"key":"e_1_2_10_28_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI87715"},{"key":"e_1_2_10_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gah112"},{"key":"e_1_2_10_30_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0897.2001.d01-6.x"},{"key":"e_1_2_10_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2014.00175"},{"key":"e_1_2_10_32_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-00672"},{"key":"e_1_2_10_33_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.691365"},{"key":"e_1_2_10_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gal110"},{"key":"e_1_2_10_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2017.12.025"},{"key":"e_1_2_10_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep40194"},{"key":"e_1_2_10_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/aas.13960"},{"key":"e_1_2_10_38_2","doi-asserted-by":"publisher","DOI":"10.1177\/1933719112459225"},{"key":"e_1_2_10_39_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0040-1715166"},{"key":"e_1_2_10_40_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2014.2054"},{"key":"e_1_2_10_41_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.114.121616"},{"key":"e_1_2_10_42_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.102.011403"},{"key":"e_1_2_10_43_2","doi-asserted-by":"publisher","DOI":"10.4161\/viru.2.6.17719"},{"key":"e_1_2_10_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/jpc.15333"},{"key":"e_1_2_10_45_2","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/378472"},{"key":"e_1_2_10_46_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.707836"},{"key":"e_1_2_10_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejcn.2013.263"},{"key":"e_1_2_10_48_2","doi-asserted-by":"publisher","DOI":"10.3109\/14767058.2011.633672"},{"key":"e_1_2_10_49_2","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/901253"},{"key":"e_1_2_10_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2020.01.050"},{"key":"e_1_2_10_51_2","doi-asserted-by":"publisher","DOI":"10.1088\/1361-648X\/ac1824"},{"key":"e_1_2_10_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/0143-4160(93)90081-G"},{"key":"e_1_2_10_53_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.7998"},{"key":"e_1_2_10_54_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.132585"},{"key":"e_1_2_10_55_2","doi-asserted-by":"publisher","DOI":"10.1186\/1559-0275-11-40"},{"key":"e_1_2_10_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2010.10.011"},{"key":"e_1_2_10_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2013.02.004"}],"container-title":["Oxidative Medicine and Cellular Longevity"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2021\/8140667.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2021\/8140667.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2021\/8140667","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T19:13:03Z","timestamp":1723057983000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2021\/8140667"}},"subtitle":[],"editor":[{"given":"Consuelo","family":"Borr\u00e1s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":57,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1155\/2021\/8140667"],"URL":"https:\/\/doi.org\/10.1155\/2021\/8140667","archive":["Portico"],"relation":{},"ISSN":["1942-0900","1942-0994"],"issn-type":[{"value":"1942-0900","type":"print"},{"value":"1942-0994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"2021-04-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"8140667"}}