Differences in heparan sulfate production in cervical fibroblast cultures from women undergoing term and preterm delivery

Objective. An extensive remodeling of the human cervical connective tissue occurs throughout pregnancy, with a decrease in the total concentration of collagen and proteoglycans. We hypothesized that the profound changes in proteoglycan production in the cervix would be seen in corresponding cervical fibroblasts as well. Methods. Cervical biopsies were obtained from five non-pregnant women, five women undergoing elective Cesarean section, six women directly after spontaneous term parturition and four directly after spontaneous preterm parturition. By explant technique, fibroblasts were cultured from the biopsies. Subcultures of the primary fibroblasts were treated with antibodies to heparan sulfate proteoglycans and labeled with radioactive sulfate. The labeled proteoglycans were purified by ion-exchange chromatography and separated by gel electrophoresis. Results. Proteoglycan production was reduced by 50% in fibroblasts obtained from term and preterm women. In comparison to equivalent control cultures from non-pregnant women, this decline was significant. Production of the proteoglycans biglycan and perlecan was similar in term partal and preterm partal cell cultures. Biglycan production was significantly reduced (by 40%) and perlecan production was significantly induced (by 60%) compared to control cultures. Fibroblast cultures established from women with preterm delivery had significantly higher production of heparan sulfate proteoglycans than those obtained from non-pregnant donors. Heparan sulfate proteoglycans were localized to cell membranes and intracellular compartments. Conclusions. The changes in proteoglycan production in the human pregnant cervix can also be seen in corresponding cervical fibroblasts. Term partal and preterm partal cells differed from their non-pregnant counterpart, which suggests a role for proteoglycans in cervical ripening.