Uterine Remodeling During Pregnancy - Studies on the Effect of Heparin/Heparan Sulfate

Sammanfattning: During pregnancy, the uterine tissues must go through a major transformation to be able to first hold the growing fetus and then, at term, expel it through the opened birth canal (cervix). It is a requirement for successful labor that there is adequate cervical softening combined with effective myometrial contractions. This is accomplished by an extensive remodeling of the extracellular matrix in both the cervix and the uterus, executed by different types of cells and mediators in a complex interplay. The overall purpose of this project was to investigate mechanisms controlling the remodeling of the uterus and cervix before parturition. This thesis demonstrates that fibroblasts with an active pro-inflammatory phenotype are important for the transformation of the uterine cervix preceding labor. Moreover, heparan sulfate proteoglycans appear to be central for the remodeling of the cervix and uterus before parturition, as shown by the finding that heparin fragments can be used in a clinical setting to prevent protracted labor.