{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T15:29:28Z","timestamp":1781969368764,"version":"3.54.5"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2017,7,19]],"date-time":"2017-07-19T00:00:00Z","timestamp":1500422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Several miRNAs are expressed in human gestational tissue, and some have been shown to be associated with placental dysfunction and complicated pregnancy outcomes. To investigate the roles of miR-346 and miR-582-3p in adverse obstetric events, we analyzed these 2 miRNAs in three samples (maternal blood, umbilical cord blood and placenta) obtained from pregnant women in four groups, including healthy control (n = 60), preeclampsia (n = 31), preterm delivery (n = 29) and small for gestational age (n = 19) patients. The expression levels of miR-346 and miR-582-3p in all included adverse obstetric outcome groups were significantly higher in the maternal plasma samples but lower in the placenta samples (all p value &lt; 0.05). In addition, the miR-346 expression levels in fetal cord blood were also significantly lower in all of the included adverse obstetric outcome groups (all p &lt; 0.05). Multivariate analysis of the three specimens after adjusting for maternal age and gestational age at delivery gave the same results. In conclusion, aberrant miR-346 and miR-582-3p expression level in pregnancy was associated with multiple maternal and fetal complications. Their differential expression in maternal blood, umbilical cord blood and placenta could be potential biomarkers or therapeutic targets for adverse obstetric outcomes<\/jats:p>","DOI":"10.3390\/ijms18071570","type":"journal-article","created":{"date-parts":[[2017,7,20]],"date-time":"2017-07-20T04:28:26Z","timestamp":1500524906000},"page":"1570","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Differential miR-346 and miR-582-3p Expression in Association with Selected Maternal and Fetal Complications"],"prefix":"10.3390","volume":"18","author":[{"given":"Pei-Yin","family":"Tsai","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Hsiang","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"},{"name":"Department of Public Health, College of Medicine, National Cheng-Kung University, Tainan 704, Taiwan"},{"name":"Biostatistics Consulting Center, National Cheng Kung University Hospital, Tainan 704, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Ni","family":"Chen","sequence":"additional","affiliation":[{"name":"Biostatistics Consulting Center, National Cheng Kung University Hospital, Tainan 704, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Ling","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Tsz","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nrg1990","article-title":"The evolution of gene regulation by transcription factors and microRNAs","volume":"8","author":"Chen","year":"2007","journal-title":"Nat. Rev. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1152\/physiolgenomics.00034.2008","article-title":"MicroRNomics: A newly emerging approach for disease biology","volume":"33","author":"Zhang","year":"2008","journal-title":"Physiol. Genom."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1161\/ATVBAHA.109.200873","article-title":"MicroRNAs are necessary for vascular smooth muscle growth, differentiation, and function","volume":"30","author":"Albinsson","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5571","DOI":"10.21873\/anticanres.11142","article-title":"MicroRNAs: A puzzling tool in cancer diagnostics and therapy","volume":"36","author":"Benedetti","year":"2016","journal-title":"Anticancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/j.molmed.2016.07.001","article-title":"MicroRNA regulators of anxiety and metabolic disorders","volume":"22","author":"Meydan","year":"2016","journal-title":"Trends Mol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1373\/clinchem.2007.097972","article-title":"Detection and characterization of placental microRNAs in maternal plasma","volume":"54","author":"Chim","year":"2008","journal-title":"Clin. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.placenta.2012.05.009","article-title":"MicroRNA expression profiles of trophoblastic cells","volume":"33","author":"Chaiwangyen","year":"2012","journal-title":"Placenta"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1016\/j.fertnstert.2014.04.023","article-title":"MicroRNA and implantation","volume":"101","author":"Galliano","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.rbmo.2012.06.022","article-title":"Evidence that miR-133a causes recurrent spontaneous abortion by reducing HLA-G expression","volume":"25","author":"Wang","year":"2012","journal-title":"Reprod. BioMed Online"},{"key":"ref_10","first-page":"117","article-title":"Uterine microRNA signature and consequence of their dysregulation in uterine disorders","volume":"7","author":"Chegini","year":"2010","journal-title":"Anim. Reprod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jri.2011.01.004","article-title":"MicroRNAs in pregnancy","volume":"88","author":"Markert","year":"2011","journal-title":"J. Reprod. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1373\/clinchem.2011.179283","article-title":"Circulating microRNA miR-323\u20133p as a biomarker of ectopic pregnancy","volume":"58","author":"Zhao","year":"2012","journal-title":"Clin. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.placenta.2014.06.004","article-title":"Clinical applications of analysis of plasma circulating complete hydatidiform mole pregnancy-associated miRNAs in gestational trophoblastic neoplasia: A preliminary investigation","volume":"35","author":"Miura","year":"2014","journal-title":"Placenta"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ijgo.2015.01.010","article-title":"Profiling maternal plasma microRNA expression in early pregnancy to predict gestational diabetes mellitus","volume":"130","author":"Zhu","year":"2015","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/biof.1325","article-title":"miR-346 and miR-582-3p-regulated EG-VEGF expression and trophoblast invasion via matrix metalloproteinases 2 and 9","volume":"43","author":"Su","year":"2017","journal-title":"BioFactors"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2877","DOI":"10.1210\/en.2007-1633","article-title":"Prokineticin 1 signaling and gene regulation in early human pregnancy","volume":"149","author":"Evans","year":"2008","journal-title":"Endocrinology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.tem.2012.05.006","article-title":"EG-VEGF: A key endocrine factor in placental development","volume":"23","author":"Brouillet","year":"2012","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s00018-012-1141-z","article-title":"EG-VEGF controls placental growth and survival in normal and pathological pregnancies: Case of fetal growth restriction (FGR)","volume":"70","author":"Brouillet","year":"2013","journal-title":"Cell Mol. Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/ng1536","article-title":"Combinatorial microRNA target predictions","volume":"37","author":"Krek","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.ajpath.2011.04.035","article-title":"miR-210 targets iron-sulfur cluster scaffold homologue in human trophoblast cell Lines: Siderosis of interstitial trophoblasts as a novel pathology of preterm preeclampsia and small-for-gestational-age pregnancies","volume":"179","author":"Lee","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"261.e1","DOI":"10.1016\/j.ajog.2007.01.008","article-title":"Distinct subsets of microRNAs are expressed differentially in the human placentas of patients with preeclampsia","volume":"196","author":"Pineles","year":"2007","journal-title":"Am. J. Obs. Gynecol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.placenta.2010.07.001","article-title":"The levels of hypoxia-regulated microRNAs in plasma of pregnant women with fetal growth restriction","volume":"31","author":"Mouillet","year":"2010","journal-title":"Placenta"},{"key":"ref_23","unstructured":"Wang, Y., and Zhao, S. (2010). Cell Types of the Placenta. Vascular Biology of the Placenta, Morgan & Claypool Life Sciences. Chapter 4."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Larrea, E., Sole, C., Manterola, L., Goicoechea, I., Armesto, M., Arestin, M., Caffarel, M.M., Araujo, A.M., Araiz, M., and Fernandez-Mercado, M. (2016). New Concepts in Cancer Biomarkers: Circulating miRNAs in Liquid Biopsies. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17050627"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/ncomms1285","article-title":"Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells","volume":"2","author":"Mittelbrunn","year":"2011","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Salomon, C., Guanzon, D., Scholz-Romero, K., Longo, S., Correa, P., Illanes, S.E., and Rice, G.E. (2017). Placental exosomes as early biomarker of preeclampsia\u2014Potential role of exosomal microRNAs across gestation. J. Clin. Endocrinol. Metab.","DOI":"10.1210\/jc.2017-00672"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Brodowski, L., Burlakov, J., Hass, S., von Kaisenberg, C., and von Versen-H\u00f6ynck, F. (2017). Impaired functional capacity of fetal endothelial cells in preeclampsia. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0178340"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"30632","DOI":"10.1038\/srep30632","article-title":"Trophoblastic debris modifies endothelial cell transcriptome in vitro: A mechanism by which fetal cells might control maternal responses to pregnancy","volume":"6","author":"Wei","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Singh, R., Hatt, L., Ravn, K., Vogel, I., Petersen, O.B., Uldbjerg, N., and Schelde, P. (2017). Fetal cells in maternal blood for prenatal diagnosis: A love story rekindled. Biomark. Med.","DOI":"10.2217\/bmm-2017-0055"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s40291-015-0184-x","article-title":"Circulating Maternal Total Cell-Free DNA, Cell-Free Fetal DNA and Soluble Endoglin Levels in Preeclampsia: Predictors of Adverse Fetal Outcome? A Cohort Study","volume":"20","author":"AbdelHalim","year":"2016","journal-title":"Mol. Diagn. Ther."},{"key":"ref_31","unstructured":"Wang, Y., and Zhao, S. (2010). Placental Blood Circulation. Vascular Biology of the Placenta, Morgan & Claypool Life Sciences. Chapter 2."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5519","DOI":"10.3390\/ijms14035519","article-title":"MicroRNAs in human placental development and pregnancy complications","volume":"14","author":"Fu","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1002\/bdra.20782","article-title":"Expression patterns of placental microRNAs","volume":"91","author":"Mouillet","year":"2011","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.jmoldx.2011.11.003","article-title":"Absolute and relative quantification of placenta-specific microRNAs in maternal circulation with placental insufficiency\u2014Related complications","volume":"14","author":"Hromadnikova","year":"2012","journal-title":"J. Mol. Diagn."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1002\/pd.4045","article-title":"Characterization of placenta-specific microRNAs in fetal growth restriction pregnancy","volume":"33","author":"Higashijima","year":"2013","journal-title":"Prenat. Diagn."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.3892\/ijmm.2015.2338","article-title":"Differential distribution of U6 (RNU6\u20131) expression in human carcinoma tissues demonstrates the requirement for caution in the internal control gene selection for microRNA quantification","volume":"36","author":"Lou","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.bbrc.2014.10.064","article-title":"U6 is not a suitable endogenous control for the quantification of circulating microRNAs","volume":"454","author":"Xiang","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/7\/1570\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:43:18Z","timestamp":1760208198000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/7\/1570"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,19]]},"references-count":37,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2017,7]]}},"alternative-id":["ijms18071570"],"URL":"https:\/\/doi.org\/10.3390\/ijms18071570","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,19]]}}}