Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

Disordered IL-33/ST2 activation in decidualizing stromal cells prolongs uterine receptivity in women with recurrent pregnancy loss

Tools
- Tools
+ Tools

Salker, Madhuri S., Nautiyal, Jaya, Steel, Jennifer H., Webster, Zoe, Šućurović, Sandra, Nicou, Marilena, Singh, Yogesh, Dr., Lucas, Emma S., Murakami, Keisuke, Chan, Yi-Wah, James, Sean G., Abdallah, Yazan, Christian, Mark, Croy, B. A. (B. Anne), Mulac-Jericevic, Biserka, Quenby, Siobhan and Brosens, Jan J. (2012) Disordered IL-33/ST2 activation in decidualizing stromal cells prolongs uterine receptivity in women with recurrent pregnancy loss. PLoS One, Vol.7 (No.12). e52252. doi:10.1371/journal.pone.0052252 ISSN 1932-6203.

[img]
Preview
Text
WRAP_Brosens_journal.pone.0052252.pdf

Download (1436Kb) | Preview
Official URL: http://dx.doi.org/10.1371/journal.pone.0052252

Request Changes to record.

Abstract

Decidualization renders the endometrium transiently receptive to an implanting blastocyst although the underlying mechanisms remain incompletely understood. Here we show that human endometrial stromal cells (HESCs) rapidly release IL-33, a key regulator of innate immune responses, upon decidualization. In parallel, differentiating HESCs upregulate the IL-33 transmembrane receptor ST2L and other pro-inflammatory mediators before mounting a profound anti-inflammatory response that includes downregulation of ST2L and increased expression of the soluble decoy receptor sST2. We demonstrate that HESCs secrete factors permissive of embryo implantation in mice only during the pro-inflammatory phase of the decidual process. IL-33 knockdown in undifferentiated HESCs was sufficient to abrogate this pro-inflammatory decidual response. Further, sequential activation of the IL-33/ST2L/sST2 axis was disordered in decidualizing HESCs from women with recurrent pregnancy loss. Signals from these cultures prolonged the implantation window but also caused subsequent pregnancy failure in mice. Thus, Il-33/ST2 activation in HESCS drives an autoinflammatory response that controls the temporal expression of receptivity genes. Failure to constrain this response predisposes to miscarriage by allowing out-of-phase implantation in an unsupportive uterine environment.

Item Type: Journal Article
Subjects: R Medicine > RG Gynecology and obstetrics
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Reproductive Health ( - until July 2016)
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Decidua -- Physiology, Ovum implantation
Journal or Publication Title: PLoS One
Publisher: Public Library of Science
ISSN: 1932-6203
Official Date: December 2012
Dates:
DateEvent
December 2012Published
Volume: Vol.7
Number: No.12
Page Range: e52252
DOI: 10.1371/journal.pone.0052252
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Funder: University Hospitals Coventry and Warwickshire NHS Trust, Warwick Medical School, Genesis Research Trust

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics

twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us