Open Access

Maternal peripheral blood natural killer cells incorporate placenta-associated microRNAs during pregnancy

  • Authors:
    • Yoichi Ishida
    • Dongwei Zhao
    • Akihide Ohkuchi
    • Tomoyuki Kuwata
    • Hiroshi Yoshitake
    • Kazuya Yuge
    • Takami Takizawa
    • Shigeki Matsubara
    • Mitsuaki Suzuki
    • Shigeru Saito
    • Toshihiro Takizawa
  • View Affiliations

  • Published online on: March 27, 2015     https://doi.org/10.3892/ijmm.2015.2157
  • Pages: 1511-1524
  • Copyright: © Ishida et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Although recent studies have demonstrated that microRNAs (miRNAs or miRs) regulate fundamental natural killer (NK) cellular processes, including cytotoxicity and cytokine production, little is known about the miRNA‑gene regulatory relationships in maternal peripheral blood NK (pNK) cells during pregnancy. In the present study, to determine the roles of miRNAs within gene regulatory networks of maternal pNK cells, we performed comprehensive miRNA and gene expression profiling of maternal pNK cells using a combination of reverse transcription quantitative PCR (RT‑qPCR)‑based miRNA array and DNA microarray analyses and analyzed the differential expression levels between first‑ and third‑trimester pNK cells. Furthermore, we constructed regulatory networks for miRNA‑mediated gene expression in pNK cells during pregnancy by Ingenuity Pathway Analysis (IPA). PCR‑based array analysis revealed that the placenta‑derived miRNAs [chromosome 19 miRNA cluster (C19MC) miRNAs] were detected in pNK cells during pregnancy. Twenty‑five miRNAs, including six C19MC miRNAs, were significantly upregulated in the third‑ compared to first‑trimester pNK cells. The rapid clearance of C19MC miRNAs also occurred in the pNK cells following delivery. Nine miRNAs, including eight C19MC miRNAs, were significantly downregulated in the post‑delivery pNK cells compared to those of the third‑trimester. DNA microarray analysis identified 69 NK cell function‑related genes that were differentially expressed between the first‑ and third‑trimester pNK cells. On pathway and network analysis, the observed gene expression changes of pNK cells likely contribute to the increase in the cytotoxicity, as well as the cell cycle progression of third‑ compared to first‑trimester pNK cells. Thirteen of the 69 NK cell function‑related genes were significantly downregulated between the first‑ and third‑trimester pNK cells. Nine of the 13 downregulated NK‑function‑associated genes were in silico target candidates of 12 upregulated miRNAs, including C19MC miRNA miR‑512‑3p. The results of this study suggest that the transfer of placental C19MC miRNAs into maternal pNK cells occurs during pregnancy. The present study provides new insight into maternal NK cell functions.

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June 2015
Volume 35 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Copy and paste a formatted citation
APA
Ishida, Y., Zhao, D., Ohkuchi, A., Kuwata, T., Yoshitake, H., Yuge, K. ... Takizawa, T. (2015). Maternal peripheral blood natural killer cells incorporate placenta-associated microRNAs during pregnancy. International Journal of Molecular Medicine, 35, 1511-1524. https://doi.org/10.3892/ijmm.2015.2157
MLA
Ishida, Y., Zhao, D., Ohkuchi, A., Kuwata, T., Yoshitake, H., Yuge, K., Takizawa, T., Matsubara, S., Suzuki, M., Saito, S., Takizawa, T."Maternal peripheral blood natural killer cells incorporate placenta-associated microRNAs during pregnancy". International Journal of Molecular Medicine 35.6 (2015): 1511-1524.
Chicago
Ishida, Y., Zhao, D., Ohkuchi, A., Kuwata, T., Yoshitake, H., Yuge, K., Takizawa, T., Matsubara, S., Suzuki, M., Saito, S., Takizawa, T."Maternal peripheral blood natural killer cells incorporate placenta-associated microRNAs during pregnancy". International Journal of Molecular Medicine 35, no. 6 (2015): 1511-1524. https://doi.org/10.3892/ijmm.2015.2157