MicroRNAome in decidua A new approach to assess the maintenance of pregnancy

Capsule:
MicroRNA expression profiles were significantly altered between miscarriage and normal pregnancy deciduas. MicroRNA-199b-5p and SGK1 were detected to determine their interaction in pregnancy maintenance in vivo and in vitro.

Authors:
Yu Wang, M.D., Ph.D., Yang Lv, Ph.D., Liyan Wang, M.D., Chunling Gong, M.S., Jiajia Sun, M.S., Xiujuan Chen, M.D., Yan Chen, M.S., Lei Yang, Ph.D., Yan Zhang, Ph.D., Xukui Yang, B.S., Chunling Bai, Ph.D., Zhuying Wei, M.S., Guangpeng Li, Ph.D.

Volume 103, Issue 4, Pages 980-989

Abstract:

Objective:
To comparatively analyze the human microRNAomes between normal pregnant and miscarriage deciduas by an in-depth sequencing of microRNA (miRNA); and to specifically examine miRNA-199b-5p and serum/glucocorticoid regulated kinase 1 (SGK1) in vivo and in vitro for their possible roles in pregnancy maintenance.

Design:
Samples of deciduas from 6–8-week spontaneous miscarriages and normal pregnant women were irrespectively collected and comparatively analyzed by miRNA sequencing. The miR-199b-5p and SGK1 expressions were validated in vivo and in vitro.

Setting:
University research and clinical institutes.

Patient(s):
In this experimental study, samples of deciduas were obtained from October 2011 to April 2012 from 29 women with spontaneous miscarriages and 35 normal pregnant women (control group) who underwent pregnancy termination at 6–8 weeks at our university gynecology unit.

Intervention(s):
Endometrial biopsies, cell transfection, and production of an miR-199b-5p transgenic mouse model.

Main Outcome Measure(s):
In-depth sequencing of the miRNAome on human deciduas was performed for statistically significant differences in miRNA expression. Expression levels of SGK1 were detected by quantitative polymerase chain reaction and immunoblotting (Western blot) in vitro while miR-199b-5p is overexpressed or knockdown in miR-199b-5p transgenic mice.

Result(s):
Expression of the 1,921 known miRNAs was analyzed in the study. In aborted deciduas, 0.57% of the miRNAs were expressed abundantly (>10,000 transcripts per million) and represented 86.38% of all the miRNA reads. Six miRNAs were down-regulated (let-7a-5p, let-7f-5p, let-7g-5p, let-7e-5p, let-7d-5p, and miR-98), whereas miR-199b-5p was significantly up-regulated. Overexpression or knockdown of miR-199b-5p in HEK293T and Ishikawa cells decreased or increased SGK1 expression. Furthermore, overexpression of miR-199b-5p in human endometrial stromal cells or in transgenic mouse decreased SGK1 expression at the mRNA and protein levels, respectively.

Conclusion(s):
Among the miRNAomes, the abundant expression of the let-7 members was decreased in aborted samples, whereas miR-199b-5p expression was consistently increased. A significant inverse correlation was found between miR-199b-5p and SGK1 in vivo and in vitro.

  • Amanda N. Kallen

    The authors present an very nice analysis of the microRNAomes in normal and miscarried decidua. I was particularly interested in the let-7 data, as let-7 miRNAs are known to be involved in cell cycle regulation and cell proliferation (among other things). The finding of decreased let-7 levels in the aborted decidua brings to mind the question of whether this is causally related to SAB or simply reflects decreased proliferation after the occurrence of the miscarriage. Do the authors have any thoughts on this based on their current or prior work?

    • Guangpeng Li

      Sequencing analyses showed that
      let-7f-5p, let-7g-5p and let-7i-5p was highly expressed in miscarriage
      deciduas. Previous study demonstrated that let-7f-5p, let-7g-5p and let-7i-5p
      were significant down-regulated in miscarriage deciduas compared with early
      pregnancy deciduas. Furthermore, target genes of let-7f-5p, let-7g-5p and
      let-7i-5p were predicted by informatics tools. Then, the relationship between
      let-7f-5p, let-7g-5p and let-7i-5p and its candidate target genes would be
      discussed according overexpression or knockdown experiment in vitro.

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