Pelvic Chlamydial Infection Predisposes to Ectopic Pregnancy by Upregulating Integrin β1 to Promote Embryo-tubal Attachment

Syed F Ahmad, Jeremy K Brown, Lisa L Campbell, Magda Koscielniak, Catriona Oliver, Nick Wheelhouse, Gary Entrican, Stuart McFee, Gillian S Wills, Myra O McClure, Patrick J Horner, Sevasti Gaikoumelou, Kai F Lee, Hilary O D Critchley, W Colin Duncan, Andrew W Horne

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Abstract

Tubal ectopic pregnancies are a leading cause of global maternal morbidity and mortality. Previous infection with Chlamydia trachomatis is a major risk factor for tubal embryo implantation but the biological mechanism behind this association is unclear. Successful intra-uterine embryo implantation is associated with increased expression of endometrial "receptivity" integrins (cell adhesion molecules). We examined integrin expression in Fallopian tubes of women with previous C. trachomatis infection, in mice experimentally infected with C. trachomatis, in immortalised human oviductal epithelial cells (OE-E6/E7) and in an in vitro model of human embryo attachment (trophoblast spheroid-OE-E6/7 cell co-culture). Previous exposure with C. trachomatis increased Fallopian tube/oviduct integrin-subunit beta-1 (ITGB1) in women and mice compared to controls. C. trachomatis increased OE-E6/E7 cell ITGB1 expression and promoted trophoblast attachment to OE-E6/E7 cells which was negated by anti-ITGB1-antibody. We demonstrate that infection with C. trachomatis increases tubal ITGB1 expression, predisposing to tubal embryo attachment and ectopic pregnancy.

Original languageEnglish
Pages (from-to)159-165
Number of pages7
JournalEBioMedicine
Volume29
Early online date23 Feb 2018
DOIs
Publication statusPublished - 1 Mar 2019

Keywords

  • Animals
  • Cell Line
  • Chlamydia Infections/complications
  • Chlamydia trachomatis
  • Coculture Techniques
  • Disease Models, Animal
  • Embryo Implantation
  • Epithelial Cells/metabolism
  • Fallopian Tubes/metabolism
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Integrin beta1/genetics
  • Mice
  • Pregnancy
  • Pregnancy, Tubal/etiology
  • Trophoblasts/metabolism

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    Ahmad, S. F., Brown, J. K., Campbell, L. L., Koscielniak, M., Oliver, C., Wheelhouse, N., Entrican, G., McFee, S., Wills, G. S., McClure, M. O., Horner, P. J., Gaikoumelou, S., Lee, K. F., Critchley, H. O. D., Duncan, W. C., & Horne, A. W. (2019). Pelvic Chlamydial Infection Predisposes to Ectopic Pregnancy by Upregulating Integrin β1 to Promote Embryo-tubal Attachment. EBioMedicine, 29, 159-165. https://doi.org/10.1016/j.ebiom.2018.02.020