Reproduction Abstracts

Miscarriage affects one in five pregnancies and has serious physical and psychological implications for the patient. Maternal infections account for 15% of miscarriages. Chlamydia trachomatis has been associated with miscarriage however the epidemiological data to support this are conflicting. The mechanism explaining the association is also unknown. Our objective was to determine whether C. trachomatis infection leads to miscarriage by impacting upon endometrial decidualisation, a process crucial for successful embryo implantation and early pregnancy.

We developed a novel in vitro model of C. trachomatis infection and decidualised primary endometrial stromal cells. Cells exposed to progesterone and cAMP were decidualised in vitro, and were subsequently infected with C. trachomatis serovar E. U.v.-inactivated C. trachomatis and uninfected cells were used as controls. Gene of interest changes were measured both at mRNA and protein level using RT-PCR and ELISA respectively.

We demonstrated that C. trachomatis can infect and multiply in endometrial stromal cells. C. trachomatis positive inclusions containing high numbers of bacteria were detected in infected cells compared to controls 48 h post infection (>1 000 000 plasmid copies, P<0.01, n=4). Classic decidualisation marker prolactin protein levels were lower in decidualised infected cell supernatants compared to control cells (n=4, P<0.05). C. trachomatis infection induced an innate immune system response from stromal cells, as measured by CXCL8 secretion, a chemokine that attracts neutrophils (n=5, P<0.05). On the contrary, chemokines CXCL12 and CXCL16, which are known to be essential for the invasive capability of trophoblast cells, were reduced in infected decidualised cells (P<0.05, n=4 and P<0.01, n=5 respectively).

Our data suggest that C. trachomatis infection of the endometrial stromal cell compartment can result in impaired decidualisation, because markers such as prolactin, CXCL12 and CXCL16, are reduced to levels similar to those detected in non-decidualised stromal cells. This mechanism could explain the role of C. trachomatis infection in adverse pregnancy outcomes.