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Expression And Significance Of SSTR-1,SSTR-2 And E-Cad In Unexplained Recurrent Spontaneous Abortion Decidua And Chorionic Villi

Posted on:2011-05-21Degree:MasterType:Thesis
Country:ChinaCandidate:L MaFull Text:PDF
GTID:2154330332458743Subject:Obstetrics and gynecology
Abstract/Summary:PDF Full Text Request
Recurrent spontaneous abortion (RSA),refers to the identity of a partner with the occurrence 3 or more than 3 times of spontaneous abortion,and the majority of abortions occur in early pregnancy is not detected fetal heart rate. The causes of RSA was complex, common factors such as Infection factors,reproductive tract anatomical abnormalities,environmental physical and chemical factors,chromosomal abnormalities。There are still 50% of patients with unknown etiology, referred to as unexplained recurrent spontaneous abortion (URSA).Reproductive immunology considers that 1/2 of the tissue antigens that embryos carrying is different from the mother's, pregnancy, is similar to the allograft. Abortion were-considered to be the result of immune rejection of embryos, which led to allograft failure.T lymphocytes is one of the most important adaptive immune response cells in the immune system. Mature T-cells is divided into CD4+T cells and CD8+T cells according to their molecular phenotype of CD.The initial CD4+T cells differentiate into Th1,Th2 and Th3 three types of effects of Th cells secrete different cytokines, respectively, play different immune effects.Th1 and Th2 cytokines maintain dynamic balance during Normal pregnancy, but the Th2-type cytokines is in the ascendant,which is the so-called "Th2 deviation." In normal state,the Th1 and Th2 cells in dynamic balance, maintaining normal cellular and humoral immune function. Th1 cells enhance phagocyte-mediated anti-inflammatory mechanisms,in particular anti-intracellular bacterial parasite infection through secretion of IL-2,IFN-γand other cytokines. Th2 cells enhance B cell-mediated humoral immune response through the secretion of IL-4, IL-5,IL-6, IL-10. Th1-type cytokines is harmful for implantation, growth of trophoblast cell, embryonic development and fetal survival; while Th2-type cytokines play a role in immune nutrition during pregnancy, so that pregnancy can be successfully carried out.Two mutual suppression and adjustment to constitute the specific cytokine network of decidua immune microenvironment to maintain a state of equilibrium of normal pregnancy, the broken the balance may cause pathological pregnancy.The imbalance of Thl and Th2 is an important feature of URSA.During the entire period of pregnancy, under the control of ovarian hormones, endometrium secretes many cytokines,adhesion molecules and various ions to promote embryo implantation, growth and development, so that endometrium has the receptivity to the embryo.However, once endocrine dysfunction happens, appropriate micro-environment is disordered, it will generate rejection to the Embryo immunity from pregnant women, which led to abortion.Thl and Th2 imbalance and the reduce of endometrial receptivity to the embryo, are important features of recurrent abortion. SSTR participate in the immune response and inflammation regulation, lower lymphocyte activity affect cell cytokine secretion, regulate T cell differentiation and function through combination with the somatostatin corresponding, have the effect of anti-inflammatory and anti-proliferative. Separately or through the mode of action, such as the following:①By inhibiting growth hormone release, inhibit proliferation of normal cells and embryonic cells in the normal implantation, growth, development, promotion of apoptosis of embryonic cells;②By activating the MAPK pathway can be blocking cell cycle from G1 to S phase transformation and thus inhibit cell proliferation, promote and accelerate the apoptosis of trophoblast cells.③Increase PTP activity, so that tyrosine kinase dephosphorylation and inactivation or through the functional PKC-8, c-src to regulate the activity of ERK inhibition caused by cessation of cell division thus leading to apoptosis;④By stimulating the Thl cells secrete IL-4, specific Th2 cells secrete IL-2, IFN-γ, IL-4, IL-10. breaking the dynamic balance between the Th1/Th2 type cytokineLevite reported that in the presence of SS, the specific Thl cells can secrete IL-4;The specific Th2 cells can directly secrete IL-2, IFN-γ, IL-4, IL-10; The combination between SSTR and the SS can cause the occurrence of URSA by inhibiting the development of embryos, differentiation, proliferation and promote apoptosis; might as well through the break of the dynamic balance between the Th1/Th2 type cytokines.E-cad mediated cell adhesion requires its cellular composition and cytoplasm protein-protein interactions within the chain to form E-cad/catenin complex, connected with the cytoskeleton. E-cad not only play the role of the cytoskeleton, or regulate cell between the cell and matrix adhesion reaction between the important medium. To the maintenance of organizational structure and morphology play an important role. In particular, even in the epithelial cell lines and organs of the body, plays an important role in differentiation.The reduction of E-cad expression and secretion decreased the secretory function of endometrial syncytiotrophoblast cells and glandular cells.The lack of necessary cell factors such as adhesion molecules,various ions for normal pregnancy,can affect the implantation of endometrial receptivity, adhesion, blastocyst adhesion, implantation,development and also the URSA.SSTR-1,SSTR-2,E-Cad and the Thl/Th2 balance have close relationship with endometrial receptivity to the embryo,and providing a basis in methodology of using immunohistochemical in the studying of expression intensity of SSTR-1,SSTR-2,E-Cad in decidual and villous tissues of URSA. Does SSTR-1,SSTR-2,E-Cad expressed in the decidual and villous tissues of URSA patients?Does the expression of SSTR-1,SSTR-2,E-Cad related with the URSA? Whether there is correlation between the two group?Objective1 Research the expression of SSTR-1,SSTR-2,E-Cad in decidual and villous tissues in patients of URSA. Disccuss the relation between SSTR-1,SSTR-2,E-Cad;Th1/Th2 balance and endometrial receptivity in decidua and villi to study the relativity between them in URSA patients.2 From the endocrine aspects and signal transduction pathway to study SSTR-1,SSTR-2,E-Cad in the URSA.Materials and methods1 Object of study and grouping URSA group Choice from october of 2008 to april of 2009 in the treatment of Third Affiliated Hospital of Zhengzhou University gynecology outpatient URSA patients 30 cases of patients, age 25-35 years, the average (31.79±0.79) years, gestational age 8±2 weeks, the average(8.32±1.09) weeks, excluding anatomical, genetic, endocrine, infectious and other factors, unexplained miscarriage has taken place 3 times or more, is now pregnant.The clinical history, signs, B-us, HCG test determine that inevitable abortion has occurred or embryo has stops growing.Control group,30 cases of pregnant women for the same period in our hospital seeking an abortion. Meet the following conditions:age 25-35 years, the average (28.14±0.51) years, gestational age 8±2 weeks, the average (8.15±0.15) weeks, no spontaneous abortion, fetal death, stillbirth history, no abnormalities in chromosome, anatomical,endocrine and infections, autoimmune diseases, with both a normal pregnancy and childbirth history. None history of medication during pregnancy and the history of viral infection, no symptoms of threatened abortion; B-us suggests normal embryonic development.URSA group and control group have been collecting samples of patients with informed consent. 2 Specimen processing and testing methodsCollect fresh Decidua and villi of two groups, rinse the fresh Decidua and villi with normal saline immediately so as to remove the blood,fix it with 10% neutral formaldehyde for 6-24 hours, routine dehydration, stone wax-embedded, each sample is deemed to 4mm serial sectioning. To 75℃oven for half an hour, routine HE staining, villi were observed separately. By immunohistochemistry for qualitative and semi-quantitative measurement of decidual and villous tissues of SSTR-1,SSTR-2,E-cad expression. 3 Statistical analysisAll data were statistically analyzed using statistical analysis SPSS13.0 software. Different groups were compared with single-factor analysis of variance(one-way ANOVA).The same indicator for two different groups were used to compare the number of LSD test,Using linear correlation analysis to understand the relevance of the three indicators.α=0.05 as significant difference test. 1 Comparison of the general situation for research object:compared with URSA group and the control group, age and gestational age had no statistically significant P>0.01).2 The expression of SSTR-1 and SSTR-2 in the two chorionic tissue group: SSTR-1,SSTR-2 expressed mainly in the cytoplasm of trophoblast cells. The expression level ofU RSA Group was higher than control group(P<0.01)3 The expression of SSTR-1,SSTR-2 in the two decidual tissue groups: SSTR-1,SSTR-2 expressed mainly in the cytoplasm of decidual gland cells. Higher expression level of URSA Group than control group (P<0.01)4 The expression of E-cad in the two chorionic tissue group:E-cad expressed primarily in trophoblast cell membrane. The expression level of control group was higher than URSA group(P<0.01)5 The expression of E-cad in the two decidual tissue groups:E-cad expressed mainly in the membrane of trophoblast cell.Higher expression level of control group than that of URSA group(P<0.01)6 The expression level of SSTR-1 and E-Cad was negative correlation in chorionic tissue and decidual tissue in maternal-fetal interface of URSAgroup,respectively.Tiss of chorionic villi(r=-0.315,P<0.05);Tiss of decidual (r=-0.369,P<0.05)7 The expression level of SSTR-2 and E-Cad was negative correlation in chorionic tissue and decidual tissue in maternal-fetal interface of URSA group,respectively. Tiss of chorionic villi(r=-0.300,P<0.05);Tiss of decidual (r=-0.358,P<0.05)8 The expression level of SSTR-2 and E-Cad was positive correlation respectively in chorionic tissue and decidual tissue in maternal-fetal interface of URSA group.Tiss of chorionic villi(r=0.796,P<0.05);Tiss of decidual(r=0.336, P<0.05) 1 In chorionic tissue and decidual tissue of URSA group, the expression level of SSTR-1 and SSTR-2 was elevation,but the level of E-cad was descended,it is possible that SSTR-1,SSTR-2 and E-cad correlate with the onset of URSA2 Both of chorionic tissue and decidual tissue in URSA group, expression levels was negatively The correlated between SSTR-1,SSTR-2 and E-cad suggest that the synergy of SSTR-1,SSTR-2 and E-cad possiblely lead to URSA...
Keywords/Search Tags:Unexplained recurrent spontaneous abortion, Somatostatin receptor-1, Somatostatin receptor-2, E-cadherin
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