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Clinical Chemistry 54: 482-490, 2008. First published January 24, 2008; 10.1373/clinchem.2007.097972
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(Clinical Chemistry. 2008;54:482-490.)
© 2008 American Association for Clinical Chemistry, Inc.

Molecular Diagnostics and Genetics

Detection and Characterization of Placental MicroRNAs in Maternal Plasma

Stephen S.C. Chim1,2,2, Tristan K.F. Shing1,3,2, Emily C.W. Hung1,3, Tak-yeung Leung2, Tze-kin Lau1,2, Rossa W.K. Chiu1,3 and Y.M. Dennis Lo1,3,a

1 Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences;2 Department of Obstetrics and Gynaecology;3 Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China.

aAddress correspondence to this author at: Department of Chemical Pathology, Rm. 38061, 1/F, Clinical Sciences Building, Prince of Wales Hospital, 30-32 Ngan Shing St., Shatin, Hong Kong SAR. Fax 852-2636-5090; e-mail loym{at}cuhk.edu.hk.

Background: The discovery of circulating fetal nucleic acids in maternal plasma has opened up new possibilities for noninvasive prenatal diagnosis. MicroRNAs (miRNAs), a class of small RNAs, have been intensely investigated recently because of their important regulatory role in gene expression. Because nucleic acids of placental origin are released into maternal plasma, we hypothesized that miRNAs produced by the placenta would also be released into maternal plasma.

Methods: We systematically searched for placental miRNAs in maternal plasma to identify miRNAs that were at high concentrations in placentas compared with maternal blood cells and then investigated the stability and filterability of this novel class of pregnancy-associated markers in maternal plasma.

Results: In a panel of TaqMan MicroRNA Assays available for 157 well-established miRNAs, 17 occurred at concentrations >10-fold higher in the placentas than in maternal blood cells and were undetectable in postdelivery maternal plasma. The 4 most abundant of these placental miRNAs (miR-141, miR-149, miR-299-5p, and miR-135b) were detectable in maternal plasma during pregnancy and showed reduced detection rates in postdelivery plasma. The plasma concentration of miR-141 increased as pregnancy progressed into the third trimester. Compared with mRNA encoded by CSH1 [chorionic somatomammotropin hormone 1 (placental lactogen)], miR-141 was even more stable in maternal plasma, and its concentration did not decrease after filtration.

Conclusion: We have demonstrated the existence of placental miRNAs in maternal plasma and provide some information on their stability and physical nature. These findings open up a new class of molecular markers for pregnancy monitoring.






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