533: Replens prevents preterm birth by inhibiting functional changes in the cervical epithelial barrier

Abstract

Premature cervical remodeling is likely an obligatory step in the pathogenesis of spontaneous preterm birth. Previously, we have shown Replens, the vehicle used to deliver vaginal progesterone, will prevent preterm birth in an inflammatory mouse model. However, it remains unknown if Replens will have an impact on cervical remodeling. Therefore, we hypothesize Replens will prevent preterm birth and cervical remodeling by inhibiting the inflammation induced functional changes to the cervical epithelial barrier. The integrity of the epithelial cell barrier was assessed using an in vitro permeability assay. Immortalized ectocervical cells were grown in a monolayer across a semi permeable membrane at a concentration of 2 x 105 cells well. Cells were treated with 10% and 25% solutions of Replens in saline for 2 hours prior to treatment with 25ug/ml of lipopolysaccharide (LPS). After 24 hours, FITC-dextran was added for 2 hours. The extent of permeability was determined by measuring the fluorescence on the receiver plates well solution. Exposure to LPS alone significantly increased the permeability of ectocervical cells (p<0.05), and pretreatment with Replens prevented the LPS induced increase in permeability at concentrations of 10% (p<0.001) and 25% (p<0.001) compared to treatment with LPS only. These studies demonstrate Replens prevents the LPS induced breakdown of the ectocervical epithelial barrier. Further research is needed to determine if Replens can be utilized as a therapeutic agent to prevent preterm birth.