Startseite Assessing the involvement of the placental microbiome and virome in preeclampsia using non coding RNA sequencing
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Assessing the involvement of the placental microbiome and virome in preeclampsia using non coding RNA sequencing

  • Liron Yoffe ORCID logo , Amir A. Kuperman , Ofer Isakov , Danielle Haguel , Avital L. Polsky , Luba Farberov , Nir Pillar , Vyacheslav Gurevich , Izhak Haviv und Noam Shomron ORCID logo EMAIL logo
Veröffentlicht/Copyright: 11. Juni 2021

Abstract

Objectives

Preeclampsia is a dangerous pregnancy complication. The source of preeclampsia is unknown, though the placenta is believed to have a central role in its pathogenesis. An association between maternal infection and preeclampsia has been demonstrated, yet the involvement of the placental microbiome in the etiology of preeclampsia has not been determined. In this study, we examined whether preeclampsia is associated with an imbalanced microorganism composition in the placenta.

Methods

To this end, we developed a novel method for the identification of bacteria/viruses based on sequencing of small non-coding RNA, which increases the microorganism-to-host ratio, this being a major challenge in microbiome methods. We validated the method on various infected tissues and demonstrated its efficiency in detecting microorganisms in samples with extremely low bacterial/viral biomass. We then applied the method to placenta specimens from preeclamptic and healthy pregnancies. Since the placenta is a remarkably large and heterogeneous organ, we explored the bacterial and viral RNA at each of 15 distinct locations.

Results

Bacterial RNA was detected at all locations and was consistent with previous studies of the placental microbiome, though without significant differences between the preeclampsia and control groups. Nevertheless, the bacterial RNA composition differed significantly between various areas of the placenta. Viral RNA was detected in extremely low quantities, below the threshold of significance, thus viral abundance could not be determined.

Conclusions

Our results suggest that the bacterial and viral abundance in the placenta may have only limited involvement in the pathogenesis of preeclampsia. The evidence of a heterogenic bacterial RNA composition in the various placental locations warrants further investigation to capture the true nature of the placental microbiome.


Corresponding author: Noam Shomron, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, E-mail:
Liron Yoffe and Amir A. Kuperman are equal first authors.

Acknowledgments

We thank Dr. Yael Nevo-Caspi and Prof. Gidi Paret for supplying the Streptococcus Infected plasma sample. We thank Dr. David Golan and Prof. Saharon Rosset for assisting and advising in the statistics. We thank Tom Rabinowitz for his help in creating the illustration of the placenta. We thank Prof. Uri Gophna for commenting on the manuscript. This work was performed in partial fulfillment of the requirements for a PhD degree of L.Y. at the Sackler Faculty of Medicine, Tel Aviv University.

  1. Research funding: The Shomron laboratory is supported by the Adelis Foundation. L.Y. is supported by the Eshkol Fellowship of the Israel Ministry of Science, Technology, and Space.

  2. Author contributions: L Y, AAK, IH, and NS conceived and designed the experiments. AAK collected the placenta samples. AAK, DH, AP, LF, NP and VG performed the experiments. LY and OI developed the computational method. LY analyzed the data. LY, AAK and NS wrote the manuscript. All authors read and approved the final manuscript, and have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The study which was approved by the Galilee Medical Center Research Ethics Committee. All methods were performed in accordance with the relevant guidelines and regulations.

  6. Data availablity: The sequencing data are available via the European Nucleotide Archive (ENA, https://www.ebi.ac.uk/ena) under accession number PRJEB30448.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/jpm-2021-0006).


Received: 2021-01-09
Accepted: 2021-04-29
Published Online: 2021-06-11
Published in Print: 2021-11-25

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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