MicroRNA signature of epithelial-mesenchymal transition in group b streptococcal infection of the placental chorioamniotic membranes

Samantha Weed, Blair Armistead, Michelle Coleman, H. Denny Liggit, Brian Johnson, Jesse Tsai, Richard P. Beyer, Theodor K. Bammler, Nicole M. Kretzer, Ed Parker, Jeroen P. Vanderhoeven, Craig J. Bierle, Lakshmi Rajagopal, Kristina M. Adams Waldorf

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Infection-induced preterm birth is a major cause of neonatal mortality and morbidity and leads to preterm premature rupture of placental chorioamniotic membranes. The loss of amniotic epithelial cells and tensile strength preceding membrane rupture is poorly understood. We hypothesized that intrauterine bacterial infection induces changes in microRNA (miRNA) expression, leading to amniotic epithelial cell loss and membrane weakening. Methods. Ten pregnant pigtail macaques received choriodecidual inoculation of either group B Streptococcus (GBS) or saline (n = 5/group). Placental chorioamniotic membranes were studied using RNA microarray and immunohistochemistry. Chorioamniotic membranes from women with preterm premature rupture of membranes (pPROM) and normal term pregnancies were studied using transmission electron microscopy. Results. In our model, an experimental GBS infection was associated with changes in the miRNA profile in the chorioamniotic membranes consistent with epithelial to mesenchymal transition (EMT) with loss of epithelial (E-cadherin) and gain of mesenchymal (vimentin) markers. Similarly, loss of desmosomes (intercellular junctions) was seen in placental tissues from women with pPROM. Conclusions. We describe EMT as a novel mechanism for infection-associated chorioamniotic membrane weakening, which may be a common pathway for many etiologies of pPROM. Therapy based on anti-miRNA targeting of EMT may prevent pPROM due to perinatal infection.

Original languageEnglish (US)
Pages (from-to)1713-1722
Number of pages10
JournalJournal of Infectious Diseases
Volume222
Issue number10
DOIs
StatePublished - Nov 15 2020

Bibliographical note

Publisher Copyright:
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • Animal model
  • Epithelial-mesenchymal transition
  • Intrauterine infection preterm labor
  • Macaca nemestrina
  • MiR-200
  • MiR-203
  • MiR-205
  • MicroRNA
  • PPROM
  • Preterm birth

Fingerprint Dive into the research topics of 'MicroRNA signature of epithelial-mesenchymal transition in group b streptococcal infection of the placental chorioamniotic membranes'. Together they form a unique fingerprint.

Cite this