Assessing the involvement of the placental microbiome and virome in preeclampsia using non coding RNA sequencing
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Liron Yoffe
, Amir A. Kuperman
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.
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.
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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.
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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.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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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.
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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).
© 2021 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Review
- Global incidence of intraventricular hemorrhage among extremely preterm infants: a systematic literature review
- Commentary
- Professional integrity in maternal – fetal innovation and research: an essential component of perinatal medicine
- WAPM Recommendations
- WAPM-World Association of Perinatal Medicine Practice Guidelines: Fetal central nervous system examination
- Corner of Academy
- Education in developing countries and reducing maternal mortality: a forgotten piece of the puzzle?
- Original Articles – Obstetrics
- The contemporary value of dedicated preterm birth clinics for high-risk singleton pregnancies: 15-year outcomes from a leading maternal centre
- Chorioamnionitis after premature rupture of membranes in nulliparas undergoing labor induction: prostaglandin E2 vs. oxytocin
- Maternal and fetal outcomes in pregnancies with obstructive sleep apnea
- Assessing the involvement of the placental microbiome and virome in preeclampsia using non coding RNA sequencing
- Risk of metformin failure in the treatment of women with gestational diabetes
- Can we improve our ability to interpret category II fetal heart rate tracings using additional clinical parameters?
- New obstetric systemic inflammatory response syndrome criteria for early identification of high-risk of sepsis in obstetric patients
- Bacteria in the amniotic fluid without inflammation: early colonization vs. contamination
- Intertwin differences in umbilical artery pulsatility index are associated with infant survival in twin-to-twin transfusion syndrome
- Maternal and neonatal outcomes in women with disorders of lipid metabolism
- The use of PAMG-1 testing in patients with preterm labor, intact membranes and a short sonographic cervix reduces the rate of unnecessary antenatal glucocorticoid administration
- Original Articles – Neonates
- The effect of postnatal corticosteroids on growth parameters in infants with bronchopulmonary dysplasia
- Are neonatal outcomes of triplet pregnancies different from those of singletons according to gestational age?
- Impact of paternal presence and parental social-demographic characteristics on birth outcomes
- Letter to the Editor
- Comment on: “amniotic fluid embolism – implementation of international diagnosis criteria and subsequent pregnancy recurrence risk”
Artikel in diesem Heft
- Frontmatter
- Review
- Global incidence of intraventricular hemorrhage among extremely preterm infants: a systematic literature review
- Commentary
- Professional integrity in maternal – fetal innovation and research: an essential component of perinatal medicine
- WAPM Recommendations
- WAPM-World Association of Perinatal Medicine Practice Guidelines: Fetal central nervous system examination
- Corner of Academy
- Education in developing countries and reducing maternal mortality: a forgotten piece of the puzzle?
- Original Articles – Obstetrics
- The contemporary value of dedicated preterm birth clinics for high-risk singleton pregnancies: 15-year outcomes from a leading maternal centre
- Chorioamnionitis after premature rupture of membranes in nulliparas undergoing labor induction: prostaglandin E2 vs. oxytocin
- Maternal and fetal outcomes in pregnancies with obstructive sleep apnea
- Assessing the involvement of the placental microbiome and virome in preeclampsia using non coding RNA sequencing
- Risk of metformin failure in the treatment of women with gestational diabetes
- Can we improve our ability to interpret category II fetal heart rate tracings using additional clinical parameters?
- New obstetric systemic inflammatory response syndrome criteria for early identification of high-risk of sepsis in obstetric patients
- Bacteria in the amniotic fluid without inflammation: early colonization vs. contamination
- Intertwin differences in umbilical artery pulsatility index are associated with infant survival in twin-to-twin transfusion syndrome
- Maternal and neonatal outcomes in women with disorders of lipid metabolism
- The use of PAMG-1 testing in patients with preterm labor, intact membranes and a short sonographic cervix reduces the rate of unnecessary antenatal glucocorticoid administration
- Original Articles – Neonates
- The effect of postnatal corticosteroids on growth parameters in infants with bronchopulmonary dysplasia
- Are neonatal outcomes of triplet pregnancies different from those of singletons according to gestational age?
- Impact of paternal presence and parental social-demographic characteristics on birth outcomes
- Letter to the Editor
- Comment on: “amniotic fluid embolism – implementation of international diagnosis criteria and subsequent pregnancy recurrence risk”