Expression And Significance Of PTEN In Placenta Tissues With Three Kinds Of Pregnancy Complications

BackgroundsOxidative stress is refers to the imbalance between active oxygen (reactive oxygen species, ROS) generation and the antioxidant defense system. Vascular endothelial dysfunction induced by oxidative stress plays an important role in these vascular diseases, such as ischemia-reperfusion injury, hypertension, diabetes, and atherosclerosis, etc.In recent years, the pathogenesis of pathological pregnancy is a research hotspot in the field of obstetrics, many studies have shown that obvious levels of oxidative stress in pathological pregnancy. Preeclampsia (PE) and fetal growth restriction (FGR), and gestational diabetes (GDM) are three common pathological pregnancy diseases. These diseases are always higher in pregnant women and perinatal mortality, and have a impact on pregnancy outcome.There are numerous preeclampsia etiology theory; such as abnormal trophoblast cells invaded the myometrium, immune injury, vascular endothelial cell injury, genetic factors, nutritional deficiency and insulin resistance, the damage of vascular endothelial cell is a central part of the preeclampsia pathophysiological. It is the common pathways that all kinds of pathogenic factors mediated the happening of hypertensive disorder complicating pregnancy. Vascular endothelial cell injury is closely related to oxidative stress. Some studies suggested that oxidative stress may be play a key role in preeclampsia. Many scholars have found that the imbalance between Oxidation system and antioxidant system has destroyed in patients with preeclampsia. The enhanced oxidation and relatively subdued resistance of oxidation make a state of high oxidative stress. Many factors lead to fetal growth restriction,40%of the patients with unclear etiology. Such as maternal factors, fetal factors, placental factors and umbilical cord factors, any one of these various risk factors can lead to occurrence of fetal growth restriction. Many studies have shown that occurrence of FGR was closely related to the lipid peroxidation enhance and antioxidant activity weakened. Recently, studies have suggested that the occurrence and development of gestational diabetes are closely associated with oxidative stress. The expression levels of serum lipid peroxidation product in GDM is higher than in normal pregnant women. Scholars have proved that the levels of sulfur barbiturate reaction material and lipid hydroperoxide in blood plasma of Gestational diabetes patients is higher. They are the classic markers of lipid peroxidatio, it is suggest directly that there is a certain relationship between diabetes and oxidative stress.Tumor suppressor gene of PTEN with both protein and lipid phosphatase activity was found in1997, as a new tumor suppressor gene, PTEN plays an important role in many physiological activities such as cell cycle regulation, apoptosis, cell adhesion and migration, vascular endothelial cell proliferation and tumor microvascular formation. Many normal tissues have the expression of PTEN, in the early embryo development, such as stomach, liver, central and peripheral nervous system have the PTEN expression. Now a large number of documents have confirmed that many cancer diseases are closely related to loss of PTEN expression, it is speculated that the change of the expression of PTEN in various tissues and organs may have important relationship with mutations in the disease.In recent years, many studies have found that there is a certain relationship between PTEN and oxidative stress. There is a high level of oxidative stress in cancer patient, that may be inhibit the expression of PTEN, the loss of PTEN may affect the normal cell activity and lead to the occurrence of cancer. Lin Yan showed that patients with gastric cancer existed excessive oxidative stress levels and low levels of antioxidan in the body. The declining antioxidant ability of the body may reduce tumor suppressor gene PTEN mRNA and FOX03a mRNA expression.PTEN belongs to members of the family of protein tyrosine phosphatases, it is one of the most sensitive member of oxidation regulation, oxygen free radical (H2O2) can make Oxidation control of PTEN reversibility. H2O2can make PTEN inactivate by oxidation. Many experiments have confirmed that PTEN can take part in the signal transduction of PTEN/PIP3/AKT. Foreign scholars showed that H2O2can induce the catalytic center of PTEN oxidation, protein-124cysteine residue and74cysteine residue formed disulfide bond and inhibited the phosphatase activity of PTEN in dependent of time and dose. He Jianqiu intervened respectively INS cells with different concentrations of glucose and H2O2, which found that ROS concentration gradually increased, expression of PTEN significantly decreased in INS cells with high sugar and H2O2intervention. This showed that elevated intracellular ROS inhibited PTEN expression, which involved in the signaling pathway of insulin secretion. In addition, domestic scholars established the mouse embryonic fibroblast cell line mode, which made conditional knockout of PTEN gene in vitro. After the loss of Pten, intracellular catalase and Mn-SOD gene transcription levels decreased, intracellular excessive ROS formed oxidative stress, caused cell lipid oxidative damage. It was speculated that PTEN can decrease the intracellular ROS level and enhance cellular antioxidant defenses, PTEN played an important role in protecting cell from oxidative damage and maintaining intracellular redox environment.In recent years, PTEN has made great progress in tumor, but the research of gestation complications is limited, which are preeclampsia,fetal growth restriction (FGR) and gestational diabetes mellitus(GDM), PTEN protein has express in many normal tissues, but very few studies in the placenta tissue.Numerous studies showed that PTEN was closely related to oxidative stress and regulated by redox, PTEN protein have antioxidant effect, many studies showed that these pregnancy complications was closely related to the imbalance of oxidative antioxidant, the different levels of oxidative stress will affect the expression of PTEN in these pathological pregnancy?ObservationThe expression levels of PTEN protein in patients with preeclampsia, fetal growth restriction, gestational diabetes and normal pregnant women was detected by immunohistochemical method, discussed the correlation between PTEN expression levels and these diseases, explored its role in pathogenesis of Pregnancy complications, may provide new ideas for treatment of diseases.Research methods1. Between February2012and January2013,1have collected placenta tissue specimen from patients with preeclampsia, FGR, gestational diabetes and normal pregnant women in our hospital. All tissues put to10%marin fluid, and Immunohistochemical methods were used to detect.2. The different expression levels of PTEN protein was detected by immunohistochemical method in patients with preeclampsia, fetal growth restriction, gestational diabetes and normal pregnant women.3. Immunohistochemical method were used to detect PTEN protein expression levels of patients with preeclampsia, fetal growth restriction, gestational diabetes and normal pregnant women, the mean of optical density(IOD)value of PTEN protein was detected by application of imageproplus image analysis system.4. Statistical analysis:SPSS13.0statistical analysis software application for processing. The data showed by average add and subtract standard deviation. Between the two groups used the independent-samples T Test. Comparison of PTEN protein IOD value in different groups used factorial design one-way ANOVA (LSD-t-test, Dunnett’s T3test). P value of<0.05was considered statistically significant.RESULTS1. PTEN protein expression in the placenta in preeclampsia group and normal pregnant women group.Immunohistochemical results showed that PTEN was mainly present in cytoplasm and nucleus of endothelial cell in human placenta, the nucleus was blue, brown or pale yellow particles said positive expression. Accidentally nourish cell appeared positive expression. Compared with normal control group, severe and mild preeclampsia group of PTEN levels significantly decreased, the difference was statistically significant(P<0.05); level of PTEN in severe preeclampsia group was lower than the mild group, the difference was statistically significant(P<0.05).2. PTEN protein expression in the placenta in preeclampsia with FGR group, simple FGR groups and normal pregnant womenExperimental results showed that compared with the normal control group, the levels of PTEN is slightly lower in simple FGR groups, the difference was not statistically significant(P>0.05); levels of PTEN in preeclampsia with FGR group was significantly lower than the other two groups; the difference was statistically significant(P<0.05).3. PTEN protein expression in the placenta in GDM groups and normal pregnant womenImmunohistochemical results showed that PTEN was mainly present in cytoplasm and nucleus of endothelial cell in human placenta. The nucleus was blue, brown or pale yellow particles said positive expression. Part of the Syncytiotrophoblast appeared positive expression.Compared with normal pregnancy, the protein expression of PTEN was decreased in the GDM group (P<0.05).Conclusion1. PTEN was expressed in vascular endothelial cells in placental of normal pregnant women group, indicated that PTEN may play a role in maintaining normal pregnancy. 2. Expression levels of PTEN protein in Heavy preeclampsia and mild preeclampsia groups were reduced, levels of PTEN protein was decreased as the disease worsens; suggested that PTEN may be associated with the severity of the illness.3. Expression levels of PTEN in Preeclampsia with FGR group and GDM group was significantly reduced, suggested that PTEN may be affected by the pathology of these diseases.