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
Affiliations
Syed F. Ahmad
MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK
Jeremy K. Brown
MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK
Lisa L. Campbell
MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK
Magda Koscielniak
MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK
Catriona Oliver
MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK
Nick Wheelhouse
Moredun Research Institute and Napier University, Edinburgh, Midlothian, UK
Gary Entrican
Moredun Research Institute and the Roslin Institute at the University of Edinburgh, Midlothian, UK
Stuart McFee
MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK
Gillian S. Wills
Jefferiss Research Trust Laboratories, Imperial College London, London, UK
Myra O. McClure
Jefferiss Research Trust Laboratories, Imperial College London, London, UK
Patrick J. Horner
Department of Medical Microbiology, North Bristol NHS Trust, Bristol, UK
Sevasti Gaikoumelou
MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK
Kai F. Lee
Department of Obstetrics and Gynecology, The University of Hong Kong, Hong Kong, China
Hilary O.D. Critchley
MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK
W. Colin Duncan
MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK
Andrew W. Horne
MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK; Correspondening author at: MRC Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
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. Keywords: Ectopic pregnancy, Chlamydia trachomatis, Integrins, Embryo implantation, Fallopian tube
