To demonstrate that pregnancy-related complications are associated with alterations in placental microRNA expression. Gene expression of 15 C19MC microRNAs (miR-512-5p, miR-515-5p, miR-516-5p, miR-517-5p, miR-518b, miR-518f-5p, miR-519a, miR-519d, miR-519e-5p, miR-520a-5p, miR-520h, miR-524-5p, miR-525, miR-526a, and miR-526b) was assessed in placental tissues, compared between groups (21 gestational hypertension [GH], 63 preeclampsia, 36 fetal growth restriction [FGR], and 42 normal pregnancies), and correlated with the severity of the disease with respect to clinical signs, delivery date, and Doppler ultrasound parameters. The expression profile of microRNAs was different between pregnancy-related complications and controls. The downregulation of 4 of 15 (miR-517-5p, miR-519d, miR-520a-5p, and miR-525), 6 of 15 (miR-517-5p, miR-518f-5p, miR-519a, miR-519d, miR-520a-5p, and miR-525), and 11 of 15 (miR-515-5p, miR-517-5p, miR-518b, miR-518f-5p, miR-519a, miR-519d, miR-520a-5p, miR-520h, miR-524-5p, miR-525, and miR-526a) microRNAs was associated with GH, FGR, and preeclampsia, respectively. Sudden onset of severe preeclampsia requiring immediate termination of gestation and mild forms of preeclampsia (persisting for several weeks) were associated with similar microRNA expression profile (downregulation of miR-517-5p, miR-520a-5p, miR-524-5p, and miR-525). In addition, miR-519a was found to be associated with severe preeclampsia. The longer the pregnancy-related disorder lasted, the more extensive was the downregulation of microRNAs (miR-515-5p, miR-518b, miR-518f-5p, miR-519d, and miR-520h). The downregulation of some C19MC microRNAs is a common phenomenon shared between GH, preeclampsia, and FGR. On the other hand, some of the C19MC microRNAs are only downregulated just in preeclampsia.

Department of Molecular Biology and Cell Pathology 3rd Faculty of Medicine Charles University Prague Czech Republic

Institute for the Care of Mother and Child 3rd Faculty of Medicine Charles University Prague Czech Republic

Zobrazit více v PubMed

Abdulsid A., Hanretty K., and Lyall F. (2013). Heat shock protein 70 expression is spatially distributed in human placenta and selectively upregulated during labor and preeclampsia. PLoS One 8, e54540. PubMed PMC

Acar N., Soylu H., Edizer I., Ozbey O., Er H., Akkoyunlu G., Gemici B., and Ustunel I. (2014). Expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxiredoxin 6 (Prdx6) proteins in healthy and pathologic placentas of human and rat. Acta Histochem 116, 1289–300 PubMed

ACOG Committee on Practise Bulletins-Obstetrics. (2002). Diagnosis and management of preeclampsia and eclampsia. Obstet Gynecol 99, 159–167 PubMed

Akolekar R., Syngelaki A., Sarquis R., Zvanca M., and Nicolaides K.H. (2011). Prediction of early, intermediate and late pre-eclampsia from maternal factors, biophysical and biochemical markers at 11–13 weeks. Prenat Diagn 31, 66–74 PubMed

Arbeille P., Berson M., Blondeau B., Durand A., Bodard S., and Locatelli A. (1995). Quantification and monitoring of vascular resistance in the lower limbs by the Doppler method (animal model). Arch Mal Coeur Vaiss 88, 1029–1034 PubMed

Bamfo J.E., and Odibo A.O. (2011). Diagnosis and management of fetal growth restriction. J Pregnancy 2011, 640715. PubMed PMC

Bartel D.P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281–297 PubMed

Bentwich I., Avniel A., Karov Y., Aharonov R., Gilad S., Barad O., Barzilai A., Einat P., Einav U., Meiri E., Sharon E., Spector Y., and Bentwich Z. (2005). Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet 37, 766–770 PubMed

Bortolin-Cavaillé M.L., Dance M., Weber M., and Cavaillé J. (2009). C19MC microRNAs are processed from introns of large Pol-II, non-protein-coding transcripts. Nucleic Acids Res 37, 3464–3473 PubMed PMC

Cali U., Cavkaytar S., Sirvan L., and Danisman N. (2013). Placental apoptosis in preeclampsia, intrauterine growth retardation, and HELLP syndrome: an immunohistochemical study with caspase-3 and bcl-2. Clin Exp Obstet Gynecol 40, 45–48 PubMed

Calin G.A., and Croce C.M. (2006). MicroRNAs and chromosomal abnormalities in cancer cells. Oncogene 25, 6202–6210 PubMed

Chan Y.C., Banerjee J., Choi S.Y., and Sen C.K. (2012). miR-210: the master hypoxamir. Microcirculation 19, 215–223 PubMed PMC

Chaparro A., Blanlot C., Ramírez V., Sanz A., Quintero A., Inostroza C., Bittner M., Navarro M., and Illanes S.E. (2013). Porphyromonas gingivalis, Treponema denticola and toll-like receptor 2 are associated with hypertensive disorders in placental tissue: a case-control study. J Periodontal Res 48, 802–809 PubMed

Chatterjee P., Weaver L.E., Doersch K.M., Kopriva S.E., Chiasson V.L., Allen S.J., Narayanan A.M., Young K.J., Jones K.A., Kuehl T.J., and Mitchell B.M. (2012). Placental Toll-like receptor 3 and Toll-like receptor 7/8 activation contributes to preeclampsia in humans and mice. PLoS One 7, e41884. PubMed PMC

Chen L.M., Liu B., Zhao H.B., Stone P., Chen Q., and Chamley L. (2010). IL-6, TNFalpha and TGFbeta promote nonapoptotic trophoblast deportation and subsequently causes endothelial cell activation. Placenta 31, 75–80 PubMed

Chen Q., Stone P., Ching L.M., and Chamley L. (2009). A role for interleukin-6 in spreading endothelial cell activation after phagocytosis of necrotic trophoblastic material: implications for the pathogenesis of pre-eclampsia. J Pathol 217, 122–130 PubMed

Cruz-Martinez R. (2009). The role of Doppler and placental screening. Best Pract Res Clin Obstet Gynaecol 23, 845–855 PubMed

Dahlstrøm B., Esbensen Y., Vollan H., Oian P., and Bukholm G. (2010). Genome profiles in maternal blood during early onset preeclampsia and towards term. J Perinat Med 38, 601–608 PubMed

Díaz E., Cárdenas M., Ariza A.C., Larrea F., and Halhali A. (2005). Placental insulin and insulin-like growth factor I receptors in normal and preeclamptic pregnancies. Clin Biochem 38, 243–247 PubMed

Dubova E.A., Pavlov K.A., Lyapin V.M., Shchyogolev A.I., and Sukhikh G.T. (2013). Vascular endothelial growth factor and its receptors in the placental villi of pregnant patients with pre-eclampsia. Bull Exp Biol Med 154, 792–795 PubMed

Dweep H., Sticht C., Pandey P., and Gretz N. (2011). miRWalk—database: prediction of possible miRNA binding sites by “walking” the genes of three genomes. J Biomed Inform 44, 839–847 PubMed

Enquobahrie D.A., Abetew D.F., Sorensen T.K., Willoughby D., Chidambaram K., and Williams M.A. (2011). Placental microRNA expression in pregnancies complicated by preeclampsia. Am J Obstet Gynecol 204, 178.e112–e121 PubMed PMC

Fan X., Rai A., Kambham N., Sung J.F., Singh N., Petitt M., Dhal S., Agrawal R., Sutton R.E., Druzin M.L., Gambhir S.S., Ambati B.K., Cross J.C., and Nayak N.R. (2014). Endometrial VEGF induces placental sFLT1 and leads to pregnancy complications. J Clin Invest 124, 4941–4952 PubMed PMC

Farina A., Zucchini C., De Sanctis P., Morano D., Sekizawa A., Purwosunu Y., Okai T., and Rizzo N. (2011). Gene expression in chorionic villous samples at 11 weeks of gestation in women who develop pre-eclampsia later in pregnancy: implications for screening. Prenat Diagn 31, 181–185 PubMed

Fornari F., Milazzo M., Chieco P., Negrini M., Marasco E., Capranico G., Mantovani V., Marinello J., Sabbioni S., Callegari E., Cescon M., Ravaioli M., Croce C.M., Bolondi L., and Gramantieri L. (2012). In hepatocellular carcinoma miR-519d is up-regulated by p53 and DNA hypomethylation and targets CDKN1A/p21, PTEN, AKT3 and TIMP2. J Pathol 227, 275–285. Verification was performed on HepG2, Hep3B, Huh-7, SNU398, SNU449, SNU182 and SNU475 cell lines PubMed

Gharesi-Fard B., Zolghadri J., and Kamali-Sarvestani E. (2010). Proteome differences of placenta between pre-eclampsia and normal pregnancy. Placenta 31, 121–125 PubMed

Gu Y., Burlison S.A., and Wang Y. (2006). PAF levels and PAF-AH activities in placentas from normal and preeclamptic pregnancies. Placenta 27, 744–749 PubMed

Gu Y., Lewis D.F., Deere K., Groome L.J., and Wang Y. (2008). Elevated maternal IL-16 levels, enhanced IL-16 expressions in endothelium and leukocytes, and increased IL-16 production by placental trophoblasts in women with preeclampsia. J Immunol 181, 4418–4422 PubMed PMC

Guo L., Yang Q., Lu J., Li H., Ge Q., Gu W., Bai Y., and Lu Z. (2011). A comprehensive survey of miRNA repertoire and 3′ addition events in the placentas of patients with pre-eclampsia from high-throughput sequencing. PLoS One 6, e21072. PubMed PMC

Han J.Y., Kim Y.S., Cho G.J., Roh G.S., Kim H.J., Choi W.J., Paik W.Y., Rho G.J., Kang S.S., and Choi W.S. (2006). Altered gene expression of caspase-10, death receptor-3 and IGFBP-3 in preeclamptic placentas. Mol Cells 22, 168–174 PubMed

Higashijima A., Miura K., Mishima H., Kinoshita A., Jo O., Abe S., Hasegawa Y., Miura S., Yamasaki K., Yoshida A., Yoshiura K., and Masuzaki H. (2013). Characterization of placenta-specific microRNAs in fetal growth restriction pregnancy. Prenat Diagn 33, 214–222 PubMed

Hromadnikova I. (2012). Extracellular nucleic acids in maternal circulation as potential biomarkers for placental insufficiency. DNA Cell Biol 31, 1221–1232 PubMed PMC

Hromadnikova I., Dvorakova L., Kotlabova K., Kestlerova A., Hympanova L., Novotna V., Doucha J., and Krofta L. (2015). Assessment of placental and maternal stress responses in patients with pregnancy related complications via monitoring of heat shock protein mRNA levels. Mol Biol Rep 42, 625–637 PubMed

Hromadnikova I., Kotlabova K., Doucha J., Dlouha K., and Krofta L. (2012). Absolute and relative quantification of placenta-specific micrornas in maternal circulation with placental insufficiency-related complications. J Mol Diagn 14, 160–167 PubMed

Hromadnikova I., Kotlabova K., Ondrackova M., Kestlerova A., Novotna V., Hympanova L., Doucha J., and Krofta L. (2013). Circulating C19MC microRNAs in preeclampsia, gestational hypertension, and fetal growth restriction. Mediators Inflamm 2013, 186041. PubMed PMC

Hsu S.D., Chu C.H., Tsou A.P., Chen S.J., Chen H.C., Hsu P.W., Wong Y.H., Chen Y.H., Chen G.H., and Huang H.D. (2008). miRNAMap 2.0: genomic maps of microRNAs in metazoan genomes. Nucleic Acids Res 36, D165–D169 PubMed PMC

Hu Y., Li P., Hao S., Liu L., Zhao J., and Hou Y. (2009). Differential expression of microRNAs in the placentae of Chinese patients with severe pre-eclampsia. Clin Chem Lab Med 47, 923–929 PubMed

Huang Y., Chuang A., Hao H., Talbot C., Sen T., Trink B., Sidransky D., and Ratovitski E. (2011). Phospho-ΔNp63α is a key regulator of the cisplatin-induced microRNAome in cancer cells. Cell Death Differ 18, 1220–1230. Verification was performed on head and neck squamous cell carcinoma cells isolated from primary tissue at the Department of Otolaryngology/Head and Neck Surgery of the Johns Hopkins University School of Medicine. PubMed PMC

Huppertz B. (2008). Placental origins of preeclampsia: challenging the current hypothesis. Hypertension 51, 970–975 PubMed

Huppertz B., and Kingdom J.C. (2004). Apoptosis in the trophoblast—role of apoptosis in placental morphogenesis. J Soc Gynecol Investig 11, 353–362 PubMed

Hwang H.S., Kwon H.S., Sohn I.S., Park Y.W., and Kim Y.H. (2012). Increased CXCL12 expression in the placentae of women with pre-eclampsia. Eur J Obstet Gynecol Reprod Biol 160, 137–141 PubMed

Ishibashi O., Ohkuchi A., Ali M.M., Kurashina R., Luo S.S., Ishikawa T., Takizawa T., Hirashima C., Takahashi K., Migita M., Ishikawa G., Yoneyama K., Asakura H., Izumi A., Matsubara S., Takeshita T., and Takizawa T. (2012). Hydroxysteroid (17-β) dehydrogenase 1 is dysregulated by miR-210 and miR-518c that are aberrantly expressed in preeclamptic placentas: a novel marker for predicting preeclampsia. Hypertension 59, 265–273 PubMed

Ishioka S., Ezaka Y., Umemura K., Hayashi T., Endo T., and Saito T. (2006). Proteomic analysis of mechanisms of hypoxia-induced apoptosis in trophoblastic cells. Int J Med Sci 4, 36–44 PubMed PMC

Khan K.S., Wojdyla D., Say L., Gülmezoglu A.M., and van Look P.F. (2006). WHO analysis of causes of maternal death: a systematic review. Lancet 367, 1066–1074 PubMed

Khong T.Y., De Wolf F., Robertson W.B., and Brosens I. (1986). Inadequate maternal vascular response to placentation in pregnancies complicated by pre-eclampsia and by small-for-gestational age infants. Br J Obstet Gynaecol 93, 1049–1059 PubMed

Kotlabova K., Doucha J., and Hromadnikova I. (2011). Placental-specific microRNA in maternal circulation—identification of appropriate pregnancy-associated microRNAs with diagnostic potential. J Reprod Immunol 89, 185–191 PubMed

Lai E.C. (2002). Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation. Nat Genet 30, 363–364 PubMed

Lamarca B. (2012). Endothelial dysfunction. An important mediator in the pathophysiology of hypertension during pre-eclampsia. Minerva Ginecol 64, 309–320 PubMed PMC

Li P., Guo W., Du L., Zhao J., Wang Y., Liu L., Hu Y., and Hou Y. (2013). microRNA-29b contributes to pre-eclampsia through its effects on apoptosis, invasion and angiogenesis of trophoblast cells. Clin Sci (Lond) 124, 27–40 PubMed

Li Q.J., Chau J., Ebert P.J., Sylvester G., Min H., Liu G., Braich R., Manoharan M., Soutschek J., Skare P., Klein L.O., Davis M.M., and Chen C.Z. (2007). miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell 129, 147–161 PubMed

Liang Y., Ridzon D., Wong L., and Chen C. (2007). Characterization of microRNA expression profiles in normal human tissues. BMC Genomics 8, 166. PubMed PMC

Lim R., Barker G., and Lappas M. (2014). The TLR2 ligand FSL-1 and the TLR5 ligand Flagellin mediate pro-inflammatory and pro-labour response via MyD88/TRAF6/NF-κB-dependent signalling. Am J Reprod Immunol 71, 401–417 PubMed

Lin S., Cheung W.K., Chen S., Lu G., Wang Z., Xie D., Li K., Lin M.C., and Kung H.F. (2010). Computational identification and characterization of primate-specific microRNAs in human genome. Comput Biol Chem 34, 232–241 PubMed

Livak K.J., and Schmittgen T.D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 25, 402–408 PubMed

Lockwood C.J., Yen C.F., Basar M., Kayisli U.A., Martel M., Buhimschi I., Buhimschi C., Huang S.J., Krikun G., and Schatz F. (2008). Preeclampsia-related inflammatory cytokines regulate interleukin-6 expression in human decidual cells. Am J Pathol 172, 1571–1579 PubMed PMC

Maccani M.A., Padbury J.F., and Marsit C.J. (2011). miR-16 and miR-21 expression in the placenta is associated with fetal growth. PLoS One 6, e21210. PubMed PMC

Martinelli R., Nardelli C., Pilone V., Buonomo T., Liguori R., Castanò I., Buono P., Masone S., Persico G., Forestieri P., Pastore L., and Sacchetti L. (2010). miR-519d overexpression is associated with human obesity. Obesity (Silver Spring) 18, 2170–2176. Verification was performed on human embryonic kidney-293 cells and poietics primary human visceral preadipocytes PubMed

Maynard S.E., Min J.Y., Merchan J., Lim K.H., Li J., Mondal S., Libermann T.A., Morgan J.P., Sellke F.W., Stillman I.E., Epstein F.H., Sukhatme V.P., and Karumanchi S.A. (2003). Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 111, 649–658 PubMed PMC

Mayor-Lynn K., Toloubeydokhti T., Cruz A.C., and Chegini N. (2011). Expression profile of microRNAs and mRNAs in human placentas from pregnancies complicated by preeclampsia and preterm labor. Reprod Sci 18, 46–56 PubMed PMC

Mellembakken J.R., Aukrust P., Olafsen M.K., Ueland T., Hestdal K., and Videm V. (2002). Activation of leukocytes during the uteroplacental passage in preeclampsia. Hypertension 39, 155–160 PubMed

Meng T., Chen H.Y., Li J., and Shang T. (2008). Expression of lectin-liked oxidized low density lipoprotein receptor-1 and apoptosis associated genes in placenta and the relationship thereof with morbility of early-onset preeclampsia. Zhonghua Yi Xue Za Zhi 88, 2633–2635 PubMed

Miko E., Meggyes M., Bogar B., Schmitz N., Barakonyi A., Varnagy A., Farkas B., Tamas P., Bodis J., Szekeres-Bartho J., Illes Z., and Szereday L. (2013). Involvement of Galectin-9/TIM-3 pathway in the systemic inflammatory response in early-onset preeclampsia. PLoS One 8, e71811. PubMed PMC

Morales-Prieto D.M., Ospina-Prieto S., Chaiwangyen W., Schoenleben M., and Markert U.R. (2013). Pregnancy-associated miRNA-clusters. J Reprod Immunol 97, 51–61 PubMed

Neale D.M., and Mor G. (2005).The role of Fas mediated apoptosis in preeclampsia. J Perinat Med 33, 471–477 PubMed

Nelson D.M. (1996). Apoptotic changes occur in syncytiotrophoblast of human placental villi where fibrin type fibrinoid is deposited at discontinuities in the villous trophoblast. Placenta 17, 387–391 PubMed

Noack F., Ribbat-Idel J., Thorns C., Chiriac A., Axt-Fliedner R., Diedrich K., and Feller A.C. (2011). miRNA expression profiling in formalin-fixed and paraffin-embedded placental tissue samples from pregnancies with severe preeclampsia. J Perinat Med 39, 267–271 PubMed

O'Connell R.M., Taganov K.D., Boldin M.P., Cheng G., and Baltimore D. (2007). MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A 104, 1604–1609 PubMed PMC

Orozco A.F., Bischoff F.Z., Horne C., Popek E., Simpson J.L., and Lewis D.E. (2006). Hypoxia-induced membrane-bound apoptotic DNA particles: potential mechanism of fetal DNA in maternal plasma. Ann N Y Acad Sci 1075, 57–62 PubMed

Oudejans C.B., Tjoa M.L., Westerman B.A., Mulders M.A., van Wijk I.J., and van Vugt J.M. (2003). Circulating trophoblast in maternal blood. Prenatal Diagn 23, 111–116 PubMed

Pineles B.L., Romero R., Montenegro D., Tarca A.L., Han Y.M., Kim Y.M., Draghici S., Espinoza J., Kusanovic J.P., Mittal P., Hassan S.S., and Kim C.J. (2007). Distinct subsets of microRNAs are expressed differentially in the human placentas of patients with preeclampsia. Am J Obstet Gynecol 196, 261.e261–e266 PubMed

Poon L.C., Akolekar R., Lachmann R., Beta J., and Nicolaides K.H. (2010). Hypertensive disorders in pregnancy: screening by biophysical and biochemical markers at 11–13 weeks. Ultrasound Obstet Gynecol 35, 662–670 PubMed

Prins J.R., Faas M.M., Melgert B.N., Huitema S., Timmer A., Hylkema M.N., and Erwich J.J. (2012). Altered expression of immune-associated genes in first-trimester human decidua of pregnancies later complicated with hypertension or foetal growth restriction. Placenta 33, 453–455 PubMed

Redman C.W., Sacks G.P., and Sargent I.L. (1999). Preeclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol 180, 499–506 PubMed

Reid G.J., Flozak A.S., and Simmons R.A. (2002). Placental expression of insulin-like growth factor receptor-1 and insulin receptor in the growth-restricted fetal rat. J Soc Gynecol Investig 9, 210–214 PubMed

Roberts J.M., and Hubel C.A. (2009). The two stage model of preeclampsia: variations on the theme. Placenta 30 Suppl A, S32–S37 PubMed PMC

Rosenfeld N., Aharonov R., Meiri E., Rosenwald S., Spector Y., Zepeniuk M., Benjamin H., Shabes N., Tabak S., Levy A., Lebanony D., Goren Y., Silberschein E., Targan N., Ben-Ari A., Gilad S., Sion-Vardy N., Tobar A., Feinmesser M., Kharenko O., Nativ O., Nass D., Perelman M., Yosepovich A., Shalmon B., Polak-Charcon S., Fridman E., Avniel A., Bentwich I., Bentwich Z., Cohen D., Chajut A., and Barshack I. (2008). MicroRNAs accurately identify cancer tissue origin. Nat Biotechnol 26, 462–469 PubMed

Schmitz U., Wolkenhauer O., and Vera J. (2013). MicroRNA Cancer Regulation: Advanced Concepts, Bioinformatics and Systems Biology Tools (Springer Science & Business Media, Berlin: ), ISBN 9400755902

Seitz H., Royo H., Bortolin M.L., Lin S.P., Ferguson-Smith A.C., and Cavaillé J. (2004). A large imprinted microRNA gene cluster at the mouse Dlk1-Gtl2 domain. Genome Res 14, 1741–1748 PubMed PMC

Sezer S.D., Küçük M., Döger F.K., Yüksel H., Odabaşi A.R., Türkmen M.K., Cakmak B.Ç., Ömürlü I.K., and Kinaş M.G. (2013). VEGF, PIGF and HIF-1α in placentas of early- and late-onset pre-eclamptic patients. Gynecol Endocrinol 29, 797–800 PubMed

Shang L.X., Wang J., Zhang L.J., Gao H., Qu D.Y., and Wang J.H. (2005). Relationship between changes of insulin like growth factor-1 and insulin like growth factor binding protein-1 in maternal serum and placenta and pathogenesis of hypertensive disorder complicating pregnancy. Zhonghua Fu Chan Ke Za Zhi 40, 516–520 PubMed

Sharp A.N., Heazell A.E., Baczyk D., Dunk C.E., Lacey H.A., Jones C.J., Perkins J.E., Kingdom J.C., Baker P.N., and Crocker I.P. (2014). Preeclampsia is associated with alterations in the p53-pathway in villous trophoblast. PLoS One 9, e87621. PubMed PMC

Stepan H., Leo C., Purz S., Höckel M., and Horn L.C. (2005). Placental localization and expression of the cell death factors BNip3 and Nix in preeclampsia, intrauterine growth retardation and HELLP syndrome. Eur J Obstet Gynecol Reprod Biol 122, 172–176 PubMed

Tal R. (2012). The role of hypoxia and hypoxia-inducible factor-1alpha in preeclampsia pathogenesis. Biol Reprod 87, 134. PubMed

Teng Y., Jiang R., Lin Q., Ding C., and Ye Z. (2010). The relationship between plasma and placental tissue factor, and tissue factor pathway inhibitors in severe pre-eclampsia patients. Thromb Res 126, e41–e45 PubMed

Tili E., Michaille J.J., Cimino A., Costinean S., Dumitru C.D., Adair B., Fabbri M., Alder H., Liu C.G., Calin G.A., and Croce C.M. (2007). Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol 179, 5082–5089 PubMed

Todros T., Marzioni D., Lorenzi T., Piccoli E., Capparuccia L., Perugini V., Cardaropoli S., Romagnoli R., Gesuita R., Rolfo A., Paulesu L., and Castellucci M. (2007). Evidence for a role of TGF-beta1 in the expression and regulation of alpha-SMA in fetal growth restricted placentae. Placenta 28, 1123–1132 PubMed

Tosun M., Celik H., Avci B., Yavuz E., Alper T., and Malatyalioğlu E. (2010). Maternal and umbilical serum levels of interleukin-6, interleukin-8, and tumor necrosis factor-alpha in normal pregnancies and in pregnancies complicated by preeclampsia. J Matern Fetal Neonatal Med 23, 880–886 PubMed

Valensise H., Vasapollo B., Gagliardi G., and Novelli G.P. (2008). Early and late preeclampsia: two different maternal hemodynamic states in the latent phase of the disease. Hypertension 52, 873–880 PubMed

von Dadelszen P., Magee L.A., and Roberts J.M. (2003). Subclassification of preeclampsia. Hypertens Pregnancy 22, 143–148 PubMed

Wang X., and El Naqa I.M. (2008). Prediction of both conserved and nonconserved microRNA targets in animals. Bioinformatics 24, 325–332 PubMed

Wataba K., Saito T., Takeuchi M., Nakayama M., Suehara N., and Kudo R. (2004). Changed expression of heat shock proteins in various pathological findings in placentas with intrauterine fetal growth restriction. Med Electron Microsc 37, 170–176 PubMed

Whitehead C.L., Walker S.P., Lappas M., and Tong S. (2013). Circulating RNA coding genes regulating apoptosis in maternal blood in severe early onset fetal growth restriction and pre-eclampsia. J Perinatol 33, 600–604 PubMed

WHO (1988) Geographic variation in the incidence of hypertension in pregnancy. World Health Organization International Collaborative Study of Hypertensive Disorders of Pregnancy. Am J Obstet Gynecol 158, 80–83 PubMed

Wieser F., Waite L., Depoix C., and Taylor R.N. (2008). PPAR Action in Human Placental Development and Pregnancy and Its Complications. PPAR Res 2008, 527048. PubMed PMC

Wilczyński J.R., Tchórzewski H., Głowacka E., Banasik M., Lewkowicz P., Szpakowski M., Zeman K., and Wilczyński J. (2002). Cytokine secretion by decidual lymphocytes in transient hypertension of pregnancy and pre-eclampsia. Mediators Inflamm 11, 105–111 PubMed PMC

Xie F., Hu Y., Turvey S.E., Magee L.A., Brunham R.M., Choi K.C., Krajden M., Leung P.C., Money D.M., Patrick D.M., Thomas E., and von Dadelszen P. (2010). Toll-like receptors 2 and 4 and the cryopyrin inflammasome in normal pregnancy and pre-eclampsia. BJOG 117, 99–108 PubMed

Xu P., Zhao Y., Liu M., Wang Y., Wang H., Li Y.X., Zhu X., Yao Y., Wang H., Qiao J., Ji L., and Wang Y.L. (2014). Variations of microRNAs in human placentas and plasma from preeclamptic pregnancy. Hypertension 63, 1276–1284 PubMed

Ye W., Lv Q., Wong C.K., Hu S., Fu C., Hua Z., Cai G., Li G., Yang B.B., and Zhang Y. (2008). The effect of central loops in miRNA: MRE duplexes on the efficiency of miRNA-mediated gene regulation. PLoS One 3, e1719 Verification was performed on COS-7 and CNE cells obtained from DMEM (GIBCO, Carlsbad, CA, USA) and Kunming Cell Bank (Kunming, China) PubMed PMC

Yoshitomi T., Kawakami K., Enokida H., Chiyomaru T., Kagara I., Tatarano S., Yoshino H., Arimura H., Nishiyama K., Seki N., and Nakagawa M. (2011). Restoration of miR-517a expression induces cell apoptosis in bladder cancer cell lines. Oncol Rep 25, 1661–1668. Verification was performed on human BC cell 25, BOY and T24 PubMed

Zhang Y., Diao Z., Su L., Sun H., Li R., Cui H., and Hu Y. (2010). MicroRNA-155 contributes to preeclampsia by down-regulating CYR61. Am J Obstet Gynecol 202, 466.e461–e467 PubMed

Zhou P., Luo X., Qi H.B., Zong W.J., Zhang H., Liu D.D., and Li Q.S. (2012). The expression of pentraxin 3 and tumor necrosis factor-alpha is increased in preeclamptic placental tissue and maternal serum. Inflamm Res 61, 1005–1012 PubMed

Zhu X.M., Han T., Sargent I.L., Yin G.W., and Yao Y.Q. (2009). Differential expression profile of microRNAs in human placentas from preeclamptic pregnancies vs normal pregnancies. Am J Obstet Gynecol 200, 661.e661–e667 PubMed

The Prediction of Gestational Hypertension, Preeclampsia and Fetal Growth Restriction via the First Trimester Screening of Plasma Exosomal C19MC microRNAs

Expression profile of C19MC microRNAs in placental tissue of patients with preterm prelabor rupture of membranes and spontaneous preterm birth