Biochemical changes in human cervical connective tissue after intracervical application of prostaglandin E2

Abstract

Cervical biopsies were taken during the first trimester from primigravidae and plurigravidae at different time points after intracervical application of prostaglandin E2-gel. Collagenase activity was determined by a highly specific technique using native, triple helical collagen as substrate. Elastase-alpha 1-proteinase-inhibitor complex (elastase) was measured by a commercially available assay, and glycosaminoglycan (GAG) analyses were performed as described by Greiling et al. (5, 6). The maximum activity of collagenase was found 2 hours after PGE2 application in plurigravidae and 4 hours after application in primigravidae. Elastase activity rose nearly 7-fold to maximum values 4 hours after PGE2 application. The total GAG concentrations and the dermatan sulfate concentrations increased by approximately 10%, while the hyaluronic acid concentrations were found to be elevated significantly by nearly 50% in the PGE2-primed cervices. We conclude that a time-dependent enzymatic collagen degradation by collagenases and other proteinases and an increase in hyaluronic acid concentrations are the significant biochemical events underlying PG-induced cervical ripening.

PIP: Clinicians applied prostaglandin E2 (PGE2) in viscous gel form to the cervixes of 38 primiparous and multiparous women in Germany and Hungary to ripen the cervix for 1st trimester abortion. They took cervical biopsies at different times after application to determine collagenase and proteinase activity and to learn the role of glycosaminoglycan (GAG) changes in PGE2-induced cervical ripening. PGE2 induced significant cervical ripening in all cases. Collagenase activity peaked 2 hours and 4 hours after PGE2-application in multigravidae and primigravidae, respectively. The increases in collagenase activity at the peak point were much higher than pretreatment levels (p .05). Elastase activity increased from 854 to 3170 ng/100 mg dry weight 4 hours after PGE2 application. Total GAG levels and dermatan sulfate levels rose insignificantly by about 10% but the hyaluronic acid levels increased significantly by almost 50%. These findings suggest that the most important biochemical events responsible for PG-induced cervical ripening include collagenases and other proteinases degrading collagen within a specified period of time and an increase in hyaluronic acid levels.