title: MicroRNA-141 is upregulated in preeclamptic placentae and regulates trophoblast invasion and intercellular communication.
abstract: Preeclampsia (PE) is one of the leading causes of maternal and perinatal morbidity and mortality worldwide. Abnormal expression of microRNAs (miRNAs) occurs in several pregnancy diseases including PE. Placental trophoblast cells express a specific set of miRNAs which changes during pregnancy. These miRNAs can be released within extracellular vesicles (EVs) and mediate intercellular communication. miR-141 is a pregnancy-related miRNA which is expressed by trophoblast cells at increased levels in maternal plasma in the third trimester. We hypothesize that miR-141 is abnormally expressed in PE placentae, controls trophoblast, and immune cell functions and is involved in the intercellular communication between fetal trophoblast and maternal immune cells. Expression of miR-141 was analyzed by quantitative real-time PCR (qPCR) in normal and preeclamptic placentae and in 2 different trophoblastic cell lines, JEG-3 and HTR-8/SVneo. Changes in JEG-3 and HTR-8/SVneo cell proliferation and invasion were investigated after miR-141 inhibition and overexpression by MTS-, BrdU-, and Matrigel assays. EVs from miR-141 transfected cells were isolated from supernatants and characterized by NanoSight analysis and qPCR. Proliferation of Jurkat T cells and invasion of HTR-8/SVneo cells were investigated after treatment with EVs containing different miR-141 levels. miR-141 expression was higher in placentae from PE patients compared with those from normal pregnancies. miR-141 inhibition in trophoblastic cells resulted in decreased cell viability and reduced invasion capability. After transfection with miR-141-mimic, trophoblastic cells secreted EVs with increased miR-141 content. These vesicles did not exert effects on trophoblastic cell invasion but reduced Jurkat T cell proliferation. In conclusion, miR-141 regulates major functions of trophoblastic and immune cells. Trophoblast cells release EVs whose miRNA content can be modified by transfection of origin cells. Furthermore, elevated levels of miR-141 can be transferred from trophoblast to immune cells by release and internalization of EVs suggesting their role in the immune regulation of normal and pathologic pregnancies.
authors.affiliation: Placenta Lab, Department of Obstetrics, University Hospital Jena, Bachstraße 18, Jena 07743, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ospina-Prieto
authors.affiliation: Placenta Lab, Department of Obstetrics, University Hospital Jena, Bachstraße 18, Jena 07743, Germany; School of Medical Sciences, University of Phayao, Phayao 56000, Thailand.
authors.forename: Wittaya
authors.initials: W
authors.lastname: Chaiwangyen
authors.affiliation: Department of Gynecology and Obstetrics, Hufeland Klinikum, Henry-van-de-Velde-Straße 2, Weimar 99425, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Herrmann
authors.affiliation: Placenta Lab, Department of Obstetrics, University Hospital Jena, Bachstraße 18, Jena 07743, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Groten
authors.affiliation: Placenta Lab, Department of Obstetrics, University Hospital Jena, Bachstraße 18, Jena 07743, Germany.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Schleussner
authors.affiliation: Placenta Lab, Department of Obstetrics, University Hospital Jena, Bachstraße 18, Jena 07743, Germany. Electronic address: markert@med.uni-jena.de.
authors.forename: Udo R
authors.initials: UR
authors.lastname: Markert
authors.affiliation: Placenta Lab, Department of Obstetrics, University Hospital Jena, Bachstraße 18, Jena 07743, Germany. Electronic address: diana.morales@med.uni-jena.de.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Morales-Prieto
mesh_terms: D000328:Adult; D001973:Bromodeoxyuridine / Q000378:metabolism; D002450:Cell Communication; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D055252:Cell-Derived Microparticles / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism; D005260:Female; D006801:Humans; D019169:Jurkat Cells; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011225:Pre-Eclampsia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D014162:Transfection; D014327:Trophoblasts / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation / Q000235:genetics*
chemical_list: C533895:MIRN141 microRNA, human; D035683:MicroRNAs; D001973:Bromodeoxyuridine