Expression Of Urokinase Plasminogen Activator, Its Receptor And Plasminogen Activator Inhibitor In The Plasma Of Pathological Pregnancy Women
Y Saleh, M Pawelec, M Siewiñski, A Karmowski, T Sebzda
plasminogen activator inhibitor-1 pai-1, urokinase-type plasminogen activator receptor upar, urokinase-type plasminogen activator upa
Y Saleh, M Pawelec, M Siewiñski, A Karmowski, T Sebzda. Expression Of Urokinase Plasminogen Activator, Its Receptor And Plasminogen Activator Inhibitor In The Plasma Of Pathological Pregnancy Women. The Internet Journal of Gynecology and Obstetrics. 2004 Volume 5 Number 1.
The invasion of trophoblast, accompanied by degradation of extracellular matrix, is crucial to normal pregnancy development. The fibrinolytic system plays a key role during pregnancy, labour and puerperium. Pathological placental invasion and pathological implantation probably plays a role in many obstetrical diseases, such as preeclampsia . The development of the hemochorial placenta requires the trophoblast to invade the endometrium, penetrating into blood vessels. Placental tissue includes components from two haplodifferent organisms. Early steps in trophoblastic development are the adhesion and invasion, which is an active process. There are correlations observed between invasion and proteinase production, like uPA, tPA and PAI-1 . Chou
The human placenta is a highly invasive structure in which a subpopulation of placental trophoblast cells invades the decidua and its vasculature to establish adequate fetal-maternal exchange. It was found that molecular mechanisms responsible for this invasion are identical to those of cancer cells; however, “unlike cancer cells, their proliferation, migration, and invasiveness in situ are stringently controlled by decidua-derived transforming growth factor (TGF)-beta” . Liu
uPA binds to its receptor, uPAR, on the surface of cancer cells, leading to the formation of plasmin. Rhabdomyosarcoma (RMS) cell lines secrete high levels of insulin-like growth factor II (IGF-II), which may indicate that autocrine IGFs play a major role in the unregulated growth and metastasis of RMS . Choi and Pai  show that tPA levels change in parallel with plasma fibrinogen concentrations during and after normal pregnancy. uPA and uPAR are central molecules for uPA/uPAR/plasmin-dependent proteolysis, which is thought to play a significant role in the development of pregnancy as well as in its many complications: pre-term pre-mature rupture of foetal membranes and placental abruption . Aflalo
Materials and Methods
The plasma was collected from pregnant women in the 1st Clinic of Obstetrics and Gynecology, Wroclaw Medical University. In our study we analyzed the expression of uPA, PAI-1 and uPAR in plasma of healthy pregnant women. We divided them into three groups: the first, the second, and the third trimester of pregnancy, 31 women in each. The fourth group (31 women) was made up of women during the first stage of labour and in the fifth group there were 33 women at 24-48 hours after delivery. All cases with processes involving fibrinolytic activation were excluded. The samples of plasma were frozen at -80°C.
Determination of uPA, PAI-1 and receptor (uPAR)
Blood sampling and the preparation of plasma for determining PAI-1, uPA and uPAR were made according to Kluft and Meijer's recommendations . Quantitative measurements of PAI-1, uPA and uPAR were carried out utilizing ELISA kits. The required dilutions, antibodies, conditions, and detection ranges for each ELISA were prepared according to the manufacturer instructions. The concentration of each protein was measured at 450 nm on a microplate reader (Dynex Technologies, Billinghurst, UK). The values for PAI-1, uPA and uPAR (ng/ml) were determined for each sample from a standard curve using Revelation Software (Dynex Technologies, Billinghurst, UK).
The data were expressed as the mean values ± SD. Walloon's rank test were used. The 0.05 level of probability was assumed as significant. The significance of the differences in median values of uPA, PAI-1 and uPAR wes calculated by Wilcoxon matched pairs signed-rank test.
The values of uPA in the first trimester (median 0.9 ng/ml, range 0.6–2.8) were statistically significantly higher (p ≤ 0.0005) than after delivery (median 0.6 ng/ml, range 0.2–1.3). The values of PAI-1 in the first trimester (median 141.0 ng/ml, range 33.2–242.3) were also statistically higher than after delivery (median 77.8 ng/ml, range 20.8–196.0) (
I) The first trimester
II) The second trimester
III) The third trimester
IV) The first stage of labour
V) 24-48 hours after delivery
The suppression of fibrinolytic activity plays an important role in the prevention of hemorrhage during pregnancy and labor. A hypofibrinolytic and hypercoagulable state may be established in the placenta during pregnancy [10,14]. Guan
It was observed that proteolitytic enzymes, especially metalloproteinase activators of plasminogen or cysteine end peptidases, play a very important role in the interaction between the developing placenta and the decidua . From the information obtained so far it becomes clear that the development of placenta is accompanied by an increase in specific proteolytic enzymes whose activities are controlled by specific inhibitors. It was noticed that these processes are controlled by specific proteins produced in the placenta [21,22]. In conclusion, we observed that the activities of uPA and PAI-1 increased gradually during pregnancy and decreased dramatically between the first stage of labour and 24-48 hours after delivery, when they reached the level lower than in the first trimester.
Yousif Saleh, PhD Department of Forensic Medicine, Molecular Technical Unit, Wroclaw Medical University, Curie-Skodowskiej 52, 50-369 Wroclaw, tel: 48717841588, e-mail: firstname.lastname@example.org