Advertisement

Differential expression profile of microRNAs in human placentas from preeclamptic pregnancies vs normal pregnancies

Published:March 16, 2009DOI:https://doi.org/10.1016/j.ajog.2008.12.045

      Objective

      The purpose of this study was to perform a comprehensive analysis of the microRNA expression profile in placentas from preeclamptic pregnancies vs normal placentas.

      Study Design

      Placentas were obtained from patients with (1) mild preeclampsia (n = 8) and (2) severe preeclampsia (n = 15) and (3) in a normal control group (n = 11) with elective cesarean delivery. The microRNA expression profile was assessed by microRNA microarray and real-time reverse transcriptase-polymerase chain reaction analysis.

      Results

      Thirty-four microRNAs were expressed differentially in preeclamptic placentas, compared with normal placentas. Of these, 11 microRNAs were overexpressed, and 23 microRNAs were underexpressed in preeclamptic pregnancies. Notably, several microRNA clusters on human chromosome 19q13.42, 13q31.3, Xq26.2, Xq26.3, and 14q32.31 (a human imprinted region) were expressed differentially in preeclamptic placentas. These results were confirmed with the use of real-time polymerase chain reaction for selected microRNAs (miR-210, -152, -411, and so on).

      Conclusion

      The results show that 34 microRNAs are deregulated in preeclamptic pregnancies, which suggests the involvement of these microRNAs in the pathogenesis of preeclampsia.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Driul L.
        • Damante G.
        • D'Elia A.
        • et al.
        Screening for pre-eclampsia in a low-risk population at 24 weeks: uterine artery Doppler flow velocimetry and genetic variants of factor V, prothrombin and methylenetetrahydrofolate reductase.
        Minerva Ginecol. 2004; 56: 385-390
        • Redman C.W.
        Current topic: pre-eclampsia and the placenta.
        Placenta. 1991; 12: 301-308
        • Pineles B.L.
        • Romero R.
        • Montenegro D.
        • et al.
        Distinct subsets of microRNAs are expressed differentially in the human placentas of patients with preeclampsia.
        Am J Obstet Gynecol. 2007; 196: 261.e1-261.e6
        • Bentwich I.
        • Avniel A.
        • Karov Y.
        • et al.
        Identification of hundreds of conserved and nonconserved human microRNAs.
        Nat Genet. 2005; 37: 766-770
        • Bushati N.
        • Cohen S.M.
        MicroRNA functions.
        Annu Rev Cell Dev Biol. 2007; 23: 175-205
        • Eisenberg I.
        • Eran A.
        • Nishino I.
        • et al.
        Distinctive patterns of microRNA expression in primary muscular disorders.
        Proc Natl Acad Sci U S A. 2007; 104: 17016-17021
        • Barad O.
        • Meiri E.
        • Avniel A.
        • et al.
        MicroRNA expression detected by oligonucleotide microarrays: system establishment and expression profiling in human tissues.
        Genome Res. 2004; 14: 2486-2494
        • Lim L.P.
        • Lau N.C.
        • Garrett-Engele P.
        • et al.
        Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs.
        Nature. 2005; 433: 769-773
        • American College of Obstetricians and Gynecologists
        • Committee on Practice Bulletins: Obstetrics
        ACOG practice bulletin no. 33: diagnosis and management of preeclampsia and eclampsia.
        Obstet Gynecol. 2002; 99: 159-167
        • National Institutes of Health
        • National Heart, Lung, and Blood Institute
        • National High Blood Pressure Education Program
        Working group report on high blood pressure in pregnancy.
        NIH, Bethesda, MD2000
        • Castoldi M.
        • Schmidt S.
        • Benes V.
        • et al.
        A sensitive array for microRNA expression profiling (miChip) based on locked nucleic acids (LNA).
        RNA. 2006; 12: 913-920
        • Tusher V.G.
        • Tibshirani R.
        • Chu G.
        Significance analysis of microarrays applied to the ionizing radiation response.
        Proc Natl Acad Sci U S A. 2001; 98: 5116-5121
        • Chen C.
        • Ridzon D.A.
        • Broomer A.J.
        • et al.
        Real-time quantification of microRNAs by stem-loop RT-PCR.
        Nucleic Acids Res. 2005; 33: e179
        • Livak K.J.
        • Schmittgen T.D.
        Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.
        Methods. 2001; 25: 402-408
        • Fasanaro P.
        • D'Alessandra Y.
        • Di Stefano V.
        • et al.
        MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine-kinase ligand Ephrin-A3.
        J Biol Chem. 2008; 283: 15878-15883
        • Tanzer A.
        • Stadler P.F.
        Molecular evolution of a microRNA cluster.
        J Mol Biol. 2004; 339: 327-335
        • Ventura A.
        • Young A.G.
        • Winslow M.M.
        • et al.
        Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters.
        Cell. 2008; 132: 875-886
        • Lu Y.
        • Thomson J.M.
        • Wong H.Y.
        • Hammond S.M.
        • Hogan B.L.
        Transgenic over-expression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells.
        Dev Biol. 2007; 310: 442-453
        • Redman C.W.
        • Sargent I.L.
        The pathogenesis of pre-eclampsia.
        Gynecol Obstet Fertil. 2001; 29: 518-522
        • Verona R.I.
        • Mann M.R.
        • Bartolomei M.S.
        Genomic imprinting: intricacies of epigenetic regulation in clusters.
        Annu Rev Cell Dev Biol. 2003; 19: 237-259
        • Williams A.E.
        • Moschos S.A.
        • Perry M.M.
        • Barnes P.J.
        • Lindsay M.A.
        Maternally imprinted microRNAs are differentially expressed during mouse and human lung development.
        Dev Dyn. 2007; 236: 572-580
        • Tycko B.
        • Morison I.M.
        Physiological functions of imprinted genes.
        J Cell Physiol. 2002; 192: 245-258
        • Seitz H.
        • Royo H.
        • Bortolin M.L.
        • Lin S.P.
        • Ferguson-Smith A.C.
        • Cavaillé J.
        A large imprinted microRNA gene cluster at the mouse Dlk1-Gtl2 domain.
        Genome Res. 2004; 14: 1741-1748
        • Halhali A.
        • Díaz L.
        • Avila E.
        • Ariza A.C.
        • Garabédian M.
        • Larrea F.
        Decreased fractional urinary calcium excretion and serum 1,25-dihydroxyvitamin D and IGF-I levels in preeclampsia.
        J Steroid Biochem Mol Biol. 2007; 103: 803-806
        • Schiessl B.
        • Mylonas I.
        • Hantschmann P.
        • et al.
        Expression of endothelial NO synthase, inducible NO synthase, and estrogen receptors alpha and beta in placental tissue of normal, preeclamptic, and intrauterine growth-restricted pregnancies.
        J Histochem Cytochem. 2005; 53: 1441-1449
        • Tan Z.
        • Randall G.
        • Fan J.
        • et al.
        Allele-specific targeting of microRNAs to HLA-G and risk of asthma.
        Am J Hum Genet. 2007; 81: 829-834
        • Yie S.M.
        • Li L.H.
        • Li Y.M.
        • Librach C.
        HLA-G protein concentrations in maternal serum and placental tissue are decreased in preeclampsia.
        Am J Obstet Gynecol. 2004; 191: 525-529