Problem: A breakdown of the cervical epithelial barrier has been associated with preterm cervical remodeling. It is unknown if Replens, the vehicle for vaginal progesterone, alters cervical epithelial junctional proteins impacting cervical remodeling and preterm birth.
Method of study: E17 CD-1 pregnant mice received an intrauterine injection of saline or lipopolysaccharide (LPS). Effect of intravaginal Replens given on day E16 and on E17 coincident with LPS was tested. A second experiment determined if an antibody to the interferon receptor (IFNaR) blocked the effects of LPS. Mice were killed after six hours, the preterm birth rate was recorded, and the serum and cervices were collected for analysis. Additionally, the epithelial cell barrier was assessed using an in vitro permeability assay.
Results: Replens decreased the rate of LPS-induced preterm birth within six hours, from 87.5% to 37.5% (P < .005). LPS + IFNaR antibody decreased the rate of preterm birth or vaginal bleeding compared to LPS + control antibody mice, 43.8% vs 87%, respectively (P < .01). E-Cadherin in the mouse serum was increased by LPS, an effect mitigated by treatment with Replens (P < .0001) or the IFNaR antibody (P < .01). Replens + LPS decreased the expression of IFN-β (P < .01). The anti-IFNaR, as well as Replens, decreased the expression of MMP13 (P < .05) compared to LPS mice. Replens also prevented the LPS-induced increase in permeability (P < .001).
Conclusion: Replens prevents preterm birth by decreasing the interferon-induced upregulation of MMP13 and the degradation of the cell adhesion protein E-Cadherin. Further studies are needed to determine if Replens can be useful as treatment for preterm birth.
Keywords: cervical remodeling; inflammation; preterm birth.
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.