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Molecular Diagnostics and Genetics |
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.
The following articles in journals at HighWire Press have cited this article:
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  X. Ji, R. Takahashi, Y. Hiura, G. Hirokawa, Y. Fukushima, and N. Iwai Plasma miR-208 as a Biomarker of Myocardial Injury Clin. Chem., November 1, 2009; 55(11): 1944 - 1949. [Abstract] [Full Text] [PDF]
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 E K O Ng, W W S Chong, H Jin, E K Y Lam, V Y Shin, J Yu, T C W Poon, S S M Ng, and J J Y Sung Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening Gut, October 1, 2009; 58(10): 1375 - 1381. [Abstract] [Full Text] [PDF]
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 S.-S. Luo, O. Ishibashi, G. Ishikawa, T. Ishikawa, A. Katayama, T. Mishima, T. Takizawa, T. Shigihara, T. Goto, A. Izumi, et al. Human Villous Trophoblasts Express and Secrete Placenta-Specific MicroRNAs into Maternal Circulation via Exosomes Biol Reprod, October 1, 2009; 81(4): 717 - 729. [Abstract] [Full Text] [PDF]
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 N. J. Park, H. Zhou, D. Elashoff, B. S. Henson, D. A. Kastratovic, E. Abemayor, and D. T. Wong Salivary microRNA: Discovery, Characterization, and Clinical Utility for Oral Cancer Detection Clin. Cancer Res., September 1, 2009; 15(17): 5473 - 5477. [Abstract] [Full Text] [PDF]
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 E C W Hung, R W K Chiu, and Y M D Lo Detection of circulating fetal nucleic acids: a review of methods and applications J. Clin. Pathol., April 1, 2009; 62(4): 308 - 313. [Abstract] [Full Text] [PDF]
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 C. F. Wright and H. Burton The use of cell-free fetal nucleic acids in maternal blood for non-invasive prenatal diagnosis Hum. Reprod. Update, January 1, 2009; 15(1): 139 - 151. [Abstract] [Full Text] [PDF]
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 P. S. Mitchell, R. K. Parkin, E. M. Kroh, B. R. Fritz, S. K. Wyman, E. L. Pogosova-Agadjanyan, A. Peterson, J. Noteboom, K. C. O'Briant, A. Allen, et al. Circulating microRNAs as stable blood-based markers for cancer detection PNAS, July 29, 2008; 105(30): 10513 - 10518. [Abstract] [Full Text] [PDF]
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