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.
Highlights
An ectopic pregnancy is a pregnancy that implants outside the main cavity of the uterus, most commonly in the Fallopian tube
integrin-subunit beta-1 (ITGB1) Expression Is Increased in the Fallopian Tube of Non-pregnant Women with Evidence of Previous C. trachomatis Infection
We found that expression of ITGB1 mRNA was higher (P b 0.05) in Fallopian tube from women with evidence of previous C. trachomatis infection (n = 8) compared to those without (n = 18) (Fig. 1a)
Summary
An ectopic pregnancy is a pregnancy that implants outside the main cavity of the uterus, most commonly in the Fallopian tube. It occurs in 1– 2% of all pregnancies worldwide and remains the most common cause of maternal morbidity and mortality in the first trimester of pregnancy (Jurkovic and Wilkinson 2011). Due to the lack of a good in vivo animal model of tubal ectopic pregnancy (in animals the abdominal cavity is the most frequent extra-uterine implanation site) (Brown and Horne 2011), we used an in vitro human trophoblast spheroid (embryo surrogate) – Fallopian tube epithelial cell co-culture model to investigate the effect of C. trachomatis exposure and functional blockage of integrin on embryo attachment. (see Supplementary Table 1) following the protocol described in Supplementary Information (Quantitative reverse transcription PCR for integrin mRNA expression)
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