The Expression Of MVD, HIF-1α, TGF-β3 And PAI-1 In Placenta Of Severe Pre-eclampsia

Hypertensive disorder complicating pregnancy is a specific disease in pregnancy, which main clinical manifestation is temporary hypertension, proteinuria in pregnancy. It is a major cause of maternal and fetal morbidity and mortality. Its incidence rate is 9.4% inland and 7%-12% abroad. Especially, severe pre-eclampsia is dangerous to mater and fetus.So far, the etiology of hypertensive disorder complicating pregnancy has not been illuminated clearly. There are several theories about its etiology: placenta shallow invasion, vascular endothelial damage, genetic factor, alimentary deficiency, insulin resistance and so on. The major pathological change of placenta is the shallow invasion of trophoblast.The reduction of trophoblast invasion capability makes the shallow invasion, deficient remodeling of uterus spiral arteries and insufficient placenta perfusion, which cause destroy of vessel endothelium, finally lead to severe pre-eclampsia. By now, the mechanism of regulation about trophoblast invasion is unclear; hypoxia is the key point of the trophoblast invasion.Placenta shallow invasion leads to placenta villous microvessel reduction and hypoxia inadequate. Now, we usually use microvessel density (MVD) to estimate vascularization. CD34 is an appropriate marker for placental villous microvessel.Recently, the role of hypoxia-inducible factor-1α(HIF-1α) in hypertensive disorder complicating pregnancy has got more and more attention. HIF-1αis a transcription factor which be generated in anoxia condition, and plays the important role in regulating the capability of trophoblast invasion, which could affect trophoblast invasion by inducing the expression of TGF-β3 and PAI-1. The abnormal high expression could reduce the trophoblast invasion capability.Transforming growth factor-beta3 (TGF-β3) is a multifunctional cytokine, relating to trophoblast differentiation, and plays the important role on negative accommodation of trophoblast invasion. Plasminogen activator inhibitor-1 (PAI-1) is a factor which regulates coagulation-fibrinolytic system. PAI-1 can effect trophoblast invasion through regulating cell adhesion and deprivation.ObjectiveThis study was designed to investigate and compare the expression of MVD, HIF-1α, TGF-β3 and PAI-1 in placental villus of normal pregnancy and severe pre-eclampsia, using immunohistochemistry and image analysis. This study will help to illuminate the process of pathophysiology of severe pre-eclampsia, to supply some theoretic foundation about regulation of trophoblast invasion and to supply some new methods about diagnosis, prevention, treatment of pre-eclampsia.Materials and Methods1. Object of research: The study population consists of 50 in-patients of abdominal delivery who admitted to the Third Affiliated Hospital of Zhengzhou University between Sep 2005 and May 2006(single pregnancy). Subjects were divided two group: (1) the normal group, i.e. normal controls (n=20, average age is 28.80±3.96 years old, average gestational age is 37.59±0.82 weeks); (2)the severe pre-eclampsia group (SP, n=30, average age is 30.40±3.97 years old, average gestational age is 37.11±0.96 weeks). According to the diagnostic standard (OBSTETRICS AND GYNECOLOGY edited by Yuejie, the sixth edition). All cases had no other complications of pregnancy and complications of internal medicines.2. Method: The placenta of each group was stained by HE, all samples were used for studying expression and quantification of CD34, HIF-1α, TGF-β3 and PAI-1 by immunohistochemistry staining and image analysis. All experimental data were processed by SPSS11.5.Results1. There were no statistical differences between control and severe pre-eclampsia group in maternal age and gestational age (P>0.05). The neonatal weight, placental weight and Apgar score in severe pre-eclampsia group were significantly lower than those in normal group(P<0.05), and there are positive correlation between the neonatal weight and the placental weight (r₁=0.503, P<0.05).2. Comparing the normal group, the placenta villous microvessel density of severe pre-eclampsia is significantly decreased.3. HIF-1αwas mainly located in the cytoplasm of placental villus syncytiotrophoblast and decidual cell, less in the nucleus of villus syncytiotrophoblast; some vascular endothelial cells also express HIF-1α. The level of HIF-1αin the placental villus syncytiotrophoblast of severe pre-eclampsia (85.98±5.84) was significantly higher than that of normal group(68.66±6.36) (P<0.05).4. TGF-β3 was mainly located in the cytoplasm of placental villus syncytiotrophoblast and decidual cell, less in the vascular endothelial cells. The level of TGF-β3 in the placental villus syncytiotrophoblast of severe pre-eclampsia (85.98±5.84) was significantly higher than that of normal group(68.66±6.36) (P< 0.05).5. PAI-1 was mainly located in the cytoplasm and the nucleus of placental villous syncytiotrophoblast, villous core mesenchymal cells and vascular endothelial cells, and the cytoplasm of decidual cell. The level of PAI-1 in the placental villus of severe pre-eclampsia (88.12±4.37) was significantly higher than that of normal group(67.85±3.66) (P<0.05).6. Pearson correlation analysis: In the placenta of severe pre-eclampsia group, the expression of HIF-1αwas positive correlation with that of TGF-β3(r₂=0.501, P< 0.05)and PAI-1 (r3=0.476, P<0.05); Meanwhile, there was positive correlation between the expression of TGF-β3 and PAI-1 (r₄=0.479, P<0.05).Conclusions 1. The pathologic changes of the placental villous maybe resulted from the placental ischemia and hypoxia.2. The results suggest that HIF-1αmay play the important role in the pathophysiology of severe pre-eclampsia, through regulating target gene, TGF-β3 and PAI-1. But the mechanism of HIF-1αand its target gene in the pathophysiology of severe pre-eclampsia need be investigated continually.Innovation points1. This study is the first research that study the effect and correlation of HIF-1α, TGF-β3 and PAI-1 in placenta tissue of severe pre-eclampsia. There is no same paper out and in our country.2. This study about the expression of PAI-1 in placenta tissue of severe pre-eclampsia is the first reports in our country.