| Objective: Severe preeclampsia is a pregnancy-specific complicationwith potentially serious hazard to maternal and child health. Severepreeclampsia is commonly divided into two types: severe preeclampsiaincidence before34weeks for early onset; come on later than34weeks forlate onset. The pathogenesis of preeclampsia remains unclear. In recent years,the theory of placenta shallow implantation has been widely accepted: thedamage of extravillous trophoblasts (EVT) invasion force will cause a defaultin the process of the uterine arteries remodeling, which is associated with poorplacental perfusion, ultimately leading to preeclampsia. Transcription factorsactivate protein-2(AP-2) is involved in the regulation of cell proliferation,differentiation embryogenesis and tumorigenesis. Some studies have reportedthat the inhibition of tumor cell migration and invasion behavior, could beattributed to the transcriptional regulation of expression of E-cadherin andMMP-9by AP-2α. These proteins are involved in extravillous trophoblastsinvasion process. The objectives of this study were to detect the expressions ofAP-2α, E-cadherin, MMP-9in the placental tissues of early onset and lateonset severe preeclampsia and normal pregnant women, in order to explore therelationship among the three proteins and their role in the pathogenesis ofsevere preeclampsia.Methods: Choose sixty pregnant women who had undergone cesareansection at the hospital,40severe preeclampsia were divided into early onsetsevere preeclampsia group (n=20) and late onset severe preeclampsia group(n=20). The normal pregnancy group were20healthy pregnant women. EVTwas distinguished from the decidual cells by the staining of CK7.Immunohistochemistry was employed to show the expressions of AP-2α, E-cadherin, MMP-9in villous trophoblasts and EVT of the three groups,HSCORE was used to value the staining. The expressions of AP-2α,E-cadherin, MMP-9protein were detected with Western blot in placentaltissues. Statistical analysis by SPSS16.0.Results:1The maternal age were no significant differences among the threegroups. However, the gestational age of early onset group significant lowerthan the late onset and normal control group, but late onset and normal controlgroup were no significant differences. The neonatal weight and placentalweight were statistical significance among the three groups.2HE results show that all experimental specimens exists decidua tissues.Immunohistochemical results showed that EVT cells really exist in thedecidua tissues of the placenta. AP-2α is mainly expressed in the nucleus,E-cadherin mainly located on cell membrane, MMP-9is mainly expressed incytoplasm. AP-2α and E-cadherin proteins were moderately or stronglyexpressed in the villous trophoblasts and EVT of the early onset and late onsetsevere preeclampsia groups, while MMP-9was nagatively or weaklyexpressed. The expression of E-cadherin protein in the villous trophoblastswas higher than that in the EVT cells. In the EVT of early onset severepreeclampsia, late onset severe preeclampsia and the normal pregnant group:AP-2α HSCORE scores were respectively (2.28±0.39),(1.86±0.37),(1.48±0.29), there was have significant difference among the three groups(P<0.05); The scores of E-cadherin were respectively (2.24±0.22),(1.99±0.24),(1.82±0.22), there was have significant difference among the three groups(P<0.05); The MMP-9scores of the three groups were (1.75±0.06),(2.00±0.06),(2.13±0.07), there was have significant difference among thethree groups (P<0.05). In the villous trophoblasts of early onset severepreeclampsia, late onset severe preeclampsia and the normal pregnant group:AP-2α HSCORE scores were respectively (3.02±0.06),(2.05±0.05),(1.49±0.06), there was have significant difference among the three groups (P<0.05); The scores of E-cadherin were respectively (2.89±0.33),(2.64±0.44), (2.20±0.39), there was have significant difference among the three groups (P<0.05); The MMP-9scores of the three groups were (1.60±0.13),(1.72±0.15),(2.33±0.17), there was have significant difference among the three groups (P<0.05).3Western blot results: In the placenta tissues of early onset severepreeclampsia, late onset severe preeclampsia and the normal pregnant group:the AP-2α relative expression were respectively (0.79±0.06),(0.66±0.08),(0.53±0.10), there was have significant difference among the three groups(P<0.05); the E-cadherin relative expression were respectively (1.71±0.05),(1.23±0.08),(0.61±0.07), there was have significant difference among thethree groups (P<0.05); the MMP-9relative expression were respectively(0.16±0.02),(0.21±0.02),(0.25±0.01), there was have significant differenceamong the three groups (P<0.05). Correlation analysis showed that AP-2αrelative expression was positively related to E-cadherin, and negatively relatedto MMP-9.Conclusions:1Compared with normal group, the expressions of AP-2α and E-caherinprotein in the villous trophoblasts and EVT of severe preeclampsia groupsignificantly increased, while the expression of MMP-9significantlydecreased. We suggest that the abnormal expressions of AP-2α, E-cadherinand MMP-9may impair EVT invasion force, which leads to a default of theuterine arteries remodeling, ultimately leading to severe preeclampsia.2Compared with late onset severe preeclampsia group, the expressionsof AP-2α and E-cadherin protein in the villous trophoblasts and EVT of earlyonset severe preeclampsia group significantly increased, while the expressionof MMP-9significantly decreased. Both early and late onset severepreeclampsia may be have the abnormal invasion of EVT and remodelingobstacle of the uterine arteries, just with different severity.3AP-2α relative expression was positively related to E-cadherin, andnegatively related to MMP-9. We speculate that the AP-2α may be inhibitEVT invasive potential by regulating the expression of E-cadherin and MMP-9, AP-2α plays an important role in the pathogenesis of severepreeclampsia.4The villous trophoblasts of severe preeclampsia may be exist obstaclein multiplication and differentiation. |
