Gene expression of plasminogen activation cascade components in human term gestational tissues with labour onset.

Abstract

The plasminogen activation cascade is thought to play a critical role in labour-associated remodelling events, such as fetal membrane rupture and placental separation. The aim of this study was to quantify, by Northern analysis, the gene expression of urokinase plasminogen activator (UPA), urokinase receptor (UPAR) and plasminogen activator inhibitor type-2 (PAI-2) in human gestational tissues. Amnion, choriodecidua and placenta were collected from women before, during and after spontaneous-onset labour at term. The expression of UPAR mRNA was significantly (P < 0.05) increased in amnion tissue during and after labour and delivery, compared with the before-labour group. In contrast, UPAR gene expression in choriodecidua and placenta was not significantly altered in association with labour onset. PAI-2 mRNA expression was also significantly (P < 0.05) increased in amnion after labour. No statistically significant differences were observed in choriodecidua or placenta PAI-2 mRNA with labour onset. Neither was any significant effect of labour status on UPA mRNA identified in any of the tissues examined. This study is the first to describe a significant increase in UPAR and PAI-2 gene expression in human amnion tissue with labour. These data are consistent with the hypothesis that, during labour, up-regulation of UPAR expression in amnion serves to localize active UPA at the cell surface, thereby increasing proteolytic activity in fetal membranes. Increased PAI-2 in amnion after labour may provide a regulatory 'switch' to cease further proteolysis in this tissue type. In conclusion, the data obtained support the proposal that the plasminogen activation cascade contributes to the rupture of fetal membranes during active labour.