441: Common vaginal bacterial strains alter cervical epithelial barrier function through alterations in epithelial cadherin cleavage

Abstract

OBJECTIVE: A cervicovaginal (CV) community dominated by Lactobacillus crispatus is associated with good vaginal health while CV communities dominated by Lactobacillus iners and Gardnerella vaginalis are associated with increased acquisition of STDs and the presence of bacterial vaginosis. The microbiota populating the CV space may play a role in the cellular and molecular processes that govern cervical remodeling and parturition. We hypothesize that compromise of the cervical epithelial barrier promotes premature cervical remodeling and preterm birth (PTB). The objective of this study was to determine if CV bacterial strains alter the cervical epithelial barrier by increasing E-cadherin (E-Cad) cleavage. STUDY DESIGN: Human ectocervical cells (Ect1/E6E7) (Ecto) were treated with 10% sterile filtered L. crispatus, L. iners and G. vaginalis cell free supernatants (CFS) for 48 hrs. Ecto cells treated with CFS were used in cell permeability assays (n¼3). Media was collected for soluble E-Cad (sECAD), Elafin and SLPI ELISAs (n¼3) and immunofluorescence microscopy was performed for E-Cad localization. RESULTS: Cell permeability was unchanged after exposure to L. crispatus CFS and increased with L. iners (p<0.001) and G. vaginalis (p<0.001) CFS exposure. sECAD was unchanged in Ecto cells exposed to L. crispatus CFS while treatment with L. iners (p<0.01) and G. vaginalis (p<0.001) CSF was increased. Immunofluorescent staining showed similar membrane localization of E-Cad in L. crispatus treated and non-treated cells while L. iners and G. vaginalis CSF showed a decrease in membrane localization of E-Cad. Elafin was increased by G. vaginalis CFS only (p<0.01) while SLPI was increased by all three bacterial CFSs (p<0.001). CONCLUSION: We found that L. iners and G. Vaginalis induce cervical epithelial permeability in part due to E-Cad cleavage. Induction of anti-microbial peptides (Elafin and SLPI) does not appear sufficient to prevent E-Cad cleavage in the presence of these bacteria. This study demonstrates that bacteria common to the CV microbial community have the ability to regulate cervical epithelial function and may play a role in premature cervical remodeling and PTB. (PENN MOD PRC) 442 Comparison of vaginal and intramuscular progesterone for prevention of preterm delivery in women with a prior preterm birth OBJECTIVE: The primary objective was to compare vaginal and intramuscular progesterone, for prevention of preterm birth (<37 weeks), in women with a prior spontaneous preterm birth (PTB) or mid-trimester abortion. The study also aimed to compare the incidence of births before 34 and 28 weeks period of gestation (PoG) and incidence of preterm labour (PTL) in the two groups.