| Hypertensive Disorder Complicating Pregnancy (HDCP) is a specific disease during pregnancy. The reported morbidity is 9.4% in our country and 7-12% in foreign countries. HDCP has serious influnence maternal and babie's health. It is one of the main reasons of maternal and perinatal morbidity and mortality, and leads to bad perinatal outcomes. The pathogeny of HDCP is still unclear, which has been a hot and difficalt topic of research. In recent years, many studies revealed that some factors induce "shallow implantation of placenta", such as abnormal expression of some placental specific genes, growth factors and placenta blood vessel endothelium growth factors, and recasting disorder of uterine helicine arteries, and under average of trophoblast cell's invasive ability. Trophoblast cell dysfunction plays important part in HDCP. It is considered to be key link of this disease, which is also called placenta or trophoblast cell ischemia therory.Syncytin is found specific experssion in placenta, which modulates the invation and differentiation of trophoblast cell. It is an important modulation in placental morphologic development, especially the fusion course of cytotrophoblast cell (CT) into syncytiotrophoblast cell (ST). Some studies consider that syncytin mRNA expression in placental tissue is increasing during the first and second trimester, and it is related to the active differentiation and fusion of cytotrophoblast cell and syncytiotrophoblast cell. In normal pregnancy, syncytin protein is discovered locating at the basement membrane of syncytiotrophoblast cell, while it transference to the top micro-chorion of syncytiotrophoblast cell when preeclampsia occurs. It reveals that different location of syncytin protein is relative to the pathogeny of HDCP. Down-regulated expression of syncytin may decrease syncytiotrophoblast cell formation, resulting in defection of placental villus development, cytotrophoblast cell differentiation and fusion disorder and vascular disorder. These effects lead to placental perfusion decease and trophoblast cell ischemia, which may finally result in HDCP, like preeclampsia.According to the classification of HDCP from the 6th edition of Obstetrics and Gynaecology, different stages of HDCP are divided in 4 groups with a control group. Western blot and immunohistochemical experiment are used to evaluate whether there is significant differency in syncytin protein expression from different classification or level of the disease. Meanwhile, this study collected the clinical and perinatal infromations of our cases, including proteinuria, blood pressure, postpartum hemorrhage volume, apgar score and birth weight, so that we could analyse the correlation between placental syncytin expression and maternal or babies' outcome. Severe placenta dysfunction caused by placenta formation disorder is a result of syncytin expression alteration. It is an important factor in the formation of placenta morphology and structure. By explorating syncytin's function in the development of different stages of HDCP, we found point of view of placenta growth and placenta dysfunction related disease. It probrobly will become the target gene or protein of some clinical treatment, providing basic theory for prevention, diagnosis and treatment of HDCP.Method In HDCP group, there were 45 cases of in-patients from different hospitals in ShenZhen during Janurary 2009 to September 2010, including 10 cases of pregnancy induced hypertention (PIH),15 of light preeclampsia,15 of severe preeclampsia and 5 of eclampsia.20 cases of normal delivery were selected as control group, with no other pregnancy complication and no significant difference in age, gestational weeks or parity from HDCP group (p>0.05).1. Placenta specimens of selected cases were collected. Syncytin protein expression level was tested by Western blot, and difference between groups was analysed.2. Immunohistochenmical study was applied to discover the location of syncytin protein in placenta, so that its abnormal expression in each HDCP groups could be known.3. Syncytin protein expression level, clinical indeces, Apgar score and birth weight were stastically compared between 5 groups. Correlation was examined between syncytin protein expression level and proteinuria, blood pressure, postpartum hemorrhage volume. We also made comparation of perinatal outcomes of these groups.4. Statistical Method:Statistical analyzation is executed by SPSS 13.0 software, the results are measured by mean±standard deviation(x±s), difference between groups is tested by one way-ANOVA. Levene's test is used for homogeneity test of variance. If it is not significant, SNK will be used for pairwise comparison. If it is significant, Tamhane's T2 test will be used. Pearson test is applied for correlation coefficiency. a=0.05 is the level of test.Result1. Syncytin protein was found expressed in all 5 groups. The syncytin protein level of eclampsia group was the lowest (8.18±0.58), severe preeclampsia group (9.11±0.43), light preeclampsia group (10.84±0.84), PIH group (11.4±0.42) They were all stastically lower than that of control group (20.09±2.23) (F= 145.302, P=0.000). In HDCP groups, there was no significant difference in eclampsia group vs severe preeclampsia group (P=0.128) and light preeclampsia group vs PIH group (P=0.288). There were significant differences in other pairs (P=0.000)2. In immunohistochenmical study, syncytin protein was found in the cytoplasm of trophoblast cell in placental tissue. Syncytin protein shown tan as strong positive. Positive rate of syncytin protein were 100% in all five groups. It was mostly (+++) in control group, (+～++)in light preeclampsia group, (+/-～-+)in severe preeclampsia group and eclampsia group, and (++～+++) in PIH group.3. Proteinuria of 24 hours was significantly different between HDCP groups and control group (F=31.564 P=0.000). There was significant and strong positive correlation in syncytin protein and proteinuria(r=-0.902, P=0.000).4. Systolic pressure and diastolic pressure were significantly different between each group (F=71.156,14.611; P=0.000,0.000). There was significant and strong correlation in syncytin protein and systolic pressure(r=-0.805, P=0.000). There was significant and middling correlation in syncytin protein and diastolic pressure(r=-0.598, P=0.000).5. Postpartum hemorrhage volume was significantly different between each group (F=3.233, P=0.035). There was weak correlation in syncytin protein and postpartum hemorrhage volume.6. This study showed that both the birth weight of light preeclampsia group and severe preeclampsia group was lower than control group (3240±639.P<0.05, 3205±590, P<0.05). The birth weight of eclampsia group is only (1980±609), while that was (3448±310) in control group. There were 7 cases of mild neonatal asphyxia and 3 cases of severe neonatal asphyxia. Especially, there were 3 fetal deaths in eclampsia group (60%). (H=11.969, P=0.018);7. In HDCP groups, there was middling correlation in syncytin protein and brith weight, but there were significant differences in birth weight these groups (F=8.286 P=0.000)Conclusion1. Using Western blot and immunohistochemical study, this study confirmed that syncytin is expressed in placental trophoblast cell of normal pregnant women and HDCP patients. Again it proved that human placenta expresses syncytin gene. The results showed that comparing to control group, syncytin protein level down-regulated in 4 HDCP goups. It prompted that syncytin not only participate in trophoblast cell regulation during the whole gestation, but also may contribute to pathogenesis of HDCP.We also found that syncytin protein level of eclampsia group and severe pre eclampsia group are significantly lower than control group, suggesting that the invasing ability of trophoblast cell is decreasing as syncytin protein expression down-regulates. That might be the one of the cause of syncytiotrophoblast cell malformation and reduction, recasting disorder of uterine helicine arteries, shallow implantation of placenta and placenta hypoxia or ischemia. It plays an important part in the pathogenesis of HDCP.In pairwise comparison, there was no significant difference in eclampsia group vs severe preeclampsia group and light preeclampsia group vs PIH group. There were significant differences in other pairs. It suggested that placenta specific syncytin might have some function in placenta, and its down-regulation in HDCP might not just a pathological change of placenta. It further showed that syncytin not only contribute to pathogenesis of HDCP, it is also an important index of stage of disease. Further research could investgate how syncytin play its part in the pathogenesis and development of HDCP.2. Proteinuria of 24 hours was significantly different between HDCP groups and control group. That may be considered as the disease progress, kidney load and filtration increases, thus more albumin leak off from glomerulus, with different levels of glomerulus injury or glomerulus and renal tubule mixed injury.There was significant and strong positive correlation in syncytin protein and proteinuria. This suggests that syncytin protein down-regulation and albumin increasing in urine are highly related to the progress of HDCP.3.This study showed that the lower syncytin protein level down-regulated, the more sever neonatal asphyxia will occur. And the lower syncytin protein level down-regulated, the less brith weight will be. Both these result suggest that HDCP is highly harmful to perinatal infant, leads to severe perinatal outcome. That may because of the typical pathophysiology of HDCP, such as uterine helicine arteries spasm, recasting disorder, placenta hypoxia and ischemia, resulting in decrease of placenta reserve ability. Most researchers consider that the main reason of neonatal asphyxia in HDCP is that arteries spasm affects placenta blood perfusion, induces sudden decrease and obstruction of the blood flow in placenta intervillous space, and decreases the oxygen carring capacity of chorion, resulting in fetal anoxia and neonatal asphyxia. The basic pathophysiology of HDCP is whole body arteriola spasm and hemodynamics change cause thrombosis in every organ and placenta, then cause ischemia and necrosis. When it comes to atherosclerosis placenta, wide infarction and dysfunction villus affect the nutrition absorption of the fetus. As the gestation goes, the fetus suffers more severe anoxia and growth restriction, even fetal death.In conclusion of this study, we consider when syncytin protein down-regulared to certain level, as the desease prolong, it will seriously damage the function of trophoblast cell, resulting in shallow implantation of placenta, anoxia, ischemia and placenta dysfunction. These influences decrese the oxygen carring capacity of fetus, restrict fetal growth, even lead to serious perinatal outcome. |
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