The Expression And Significance Of Epithelial-mesenchymal Transition Related Molecules In Early Onset Severe Pre-eclampsia

Objective: Severe pre-eclampsia is a pregnancy-specific complicationwith potentially serious hazard to maternal and child health. Early onsetsevere pre-eclampsia is commonly defined as de novo hypertension andproteinuria before34weeks of gestational age. The incidence rate is about0.9%. It is characterized by rapid progress, the earlier occurrence of multipleorgans dysfunction, increased perinatal morbidity and mortality, the high riskof recurrence. Its pathogenesis is not yet fully elucidate. It is widely believedthat preeclampsia is associated with placental ischemia. Placental vascularbed's developmental disorders, will cause superficial nidaton of placenta alsoknown as the defects in the placenta.Human trophoblast cells differentiate into two major cell lineages. Theyare villous trophoblasts (VTS) and extravillous trophoblasts (EVT). Humanvillous trophoblasts form chorionic villi, covering the surface of the villi andtransporting nutrients and oxygen to the baby. EVT is able to invade maternaldecidual tissue and reconstruct the spiral arteries. The disturbance of invasioncan induce placenta dysfunction, and then lead to multifarious obstetricaldiseases. For example, shallow implants can cause preeclampsia and fetalgrowth restriction, while deep implants lead to placenta accreta and placentalsite tumor.Epithelial-mesenchymal transition(EMT) is a phenomenon which refers tothe transdifferentiation of epithelial cells to mesenchymal cells in specificphysiological and pathological condition. It is characterized by loss ofmarkers and polarity of epithelia cells(such as keratin filaments, E-cadherin)and transformation into mesenchymal morphology,gain of mesenchymal cellmarkers (such as vimentin, fibronectin, N-cadherin). Recently, many studiesfound that when tumor cell invade and metastasize, E-cadherin downregulation and cell adhesion weakened, cause tumor cells to fall offeasily from the tumor cells and transfer to other places. It is postulated thatplacenta formation is likely similar to tumor's invasion and metastasisprocess.The purpose of this study is to explore the expression of E-cadherin,N-cadherin and the transcription factor Snail, which are related to EMT, in thepatients of early onset severe pre-eclampsia. To understand the relationshipbetween EMT and early onset severe pre-eclampsia pathogenesis, mayprovide a theoretical basis of the etiology research.Methods: Placental tissues were obtained from30patients with earlyonset severe pre-eclampsia as experimental group and20patients of pretermlabor as control group. The protein expressions of cytokeratin7, E-cadherin,N-cadherin and Snail in the uteroplacental interface were detected byimmunohistochemistry and immunofluorescence double staining. Theexpression of soluble E-cadherin in venous blood taken from patients asmentioned above were measured by enzyme linked immuneosorbent assay.Result: Immunohistochemical results showed that cytokeratin7waspositively expressed both in the villous cytotrophoblasts and in decidua. It wasproved that EVT cells really exist in the decidua tissues of the uetroplacentalinterface. the brown granules were visible in the cytoplasm of E-cadherin andN-cadherin positive-expression cells, and in the nucleus or cytoplasm of Snailpositive-expression cells. E-cadherin protein was moderately or stronglyexpressed in the villous trophoblasts of placental tissues in the experimentaland control groups, while N-cadherin protein was nagatively or weaklyexpressed and Snail was moderately expressed. In the two groups, theexpression of E-cadherin protein in the villous trophoblasts was higher thanthat in the EVT cells, while the expression of N-cadherin protein and Snail inthe EVT cells were higher than that in the villous trophoblasts. The expressionof E-cadherin protein in the EVT cells of the uteroplacental interface inexperimental group was much stronger than that in the control group. Thepositive rates of E-cadherin protein in the the EVT cells in experimental group and the control group were85%and35%respectively. There was a significantdifference between two groups (P<0.001). The expression of N-cadherin andSnail in the EVT cells of the uteroplacental interface in experimental groupwere much weaker than that in the control group. The positive rates ofN-cadherin and Snail in the EVT cells in the experimental group wererespectively40%and33%, while they were82%and65%in the controlgroup. There were significant difference between two groups (P<0.001).Immunofluorescence double staining showed that red labeled withcytokeratin7was visible both in the villous trophoblasts and in EVT, whilegreen labeled with E-cadherin and Snail was visible both in the villoustrophoblasts and in EVT. Green labeled N-cadherin was visible only in theEVT. The image overlay was yellow.ELISA results showed that The level of soluble E-cadherin in the venousblood of the patients with early onset severe pre-eclampsia was (2.73±0.6)ug/mL, significantly higher than that of control group (1.81±0.14)ug/mL (P<0.001).Conclusions: EVT really exist in the decidua of the uteroplacentalinterface. Compared with control group, the expression of E-cadherin wassignificantly increased and N-cadherin and Snail expressions weresignificantly decreased in the EVT of patients with early onset severepre-eclampsia, which may be involved in the limited invasion of EVT andplay important role in the pathogenesis and development of early onset severepre-eclampsia.