244. Effects of relaxin treatment on hyaluronic synthase expression in the cervix of pregnant relaxin-deficient (Rln^−/−) mice

Abstract

The cervical extracellular matrix (ECM) changes extensively in a process called cervical ripening in late pregnancy. This occurs through a complex series of processes leading to collagen fibre degradation and dispersal. We tested the hypothesis that relaxin increases cervical water content by stimulating hyaluronic synthase (HAS) enzymes that regulate hyaluronic acid (HA) synthesis. HA is thought to recruit water molecules into interstitial spaces between collagen fibrils, causing them to disperse. In the first study, cervices were collected from Rln^+/+ and Rln^−/− mice on days 14.5, 16.5, 18.5 and 19 gestation, and day 1 postpartum (PP) to compare has expression between the genotypes by qPCR analysis. In the second study, Rln^−/− mice were implanted with Alzet osmotic minipumps on day 12.5 gestation to infuse either recombinant H2 human relaxin (200 μg/mL; BAS Medical Inc.) or 0.9% saline at a continuous flow rate of 0.5 μl/h. Cervices were collected after 4 or 6 days of infusion. has1 and has2 gene expression increased significantly at term and decreased immediately postpartum in the Rln^+/+ mice. Although has1 and has2 were expressed in Rln^−/− mice, there was no increase in expression on day 18.5 gestation and cervix wet weight did not increase compared with Rln^+/+ mice. Relaxin infusion for 4 or 6 days in pregnant Rln^−/− mice significantly increased cervical has2 but decreased has1 expression compared with saline-controls. Additionally, relaxin treatment caused a 6-fold increase in cervix wet weight, a 5% increase in water content and a significant decrease in relaxin receptor (Rxfp1) expression compared with saline-controls. These data suggest that relaxin promotes cervical hydration through an has2-mediated increase in HA, and may facilitate cervical ripening by causing collagen fibril dispersal in the ECM.