Unexplained Recurrent Spontaneous Abortion Decidua And Chorionic Villi In Patients With Tissue Stat4, Stat6 Expression

Recurrent spontaneous abortion (RSA) ,partner with the identity refers to a succession of 3 or more than 3 spontaneous abortion, RSA complex etiology, there is now specific factors: genetic defects in the structure of maternal reproductive malformations,infections,endocrine abnormalities,environmental physico chemical and mechanical factors, immune factors already have specific causes of ABO Parent, both parents of the existence of anti-sperm antibodies, anti-mother-father antibody cytotoxic lymphocytes lack of maternal endometrial antibody and antiphospholipid antibodies in pregnant women, such as excessive. In addition, about 50% RSA patients with non-existence of these causes, referred to as unexplained recurrent spontaneous abortion (URSA)。Reproductive immunology Considers, pregnancy similar to allografts, the success of pregnancy depends on the pregnant women of fetal immune tolerance shown. Abortion allografts were considered failures. With the progress of the study of immunology, and gradually realize that embryos carrying 1 / 2 is different from the mother's tissue antigens, but not maternal rejection of the substance of the immune system are dependent on relations between the maternal-fetal immune tolerance. Once this pattern of immune tolerance is broken, will lead to the occurrence of RSA.In the above-mentioned mechanism of immune tolerance "Th1/Th2 type cytokine balance" dominant doctrine. Normal pregnancy between Th1/Th2 type cytokines to maintain dynamic balance to the Th2-type cytokines dominated by the so-called "Th2 deviated from." Th1-type cytokines, mainly through the release of IL-2, IFN-γ, IFN-β, and TNF-αinhibiting T cell proliferation and IL-4 in T cell signal transduction and promoting cell-mediated immunity, involving in the occurrence of pathological pregnancy . Th2-type cytokines through the release of IL-4, IL-5, IL-10, IL-13 and other cytokines and chemokines and promotes the formation of IgE, mainly involved in humoral immunity, and protection of the role of nourishing the fetus. At the same time, many cells in the body and influence the interaction between factors, a common intervention and adjustment of the ratio of Thl/Th2 Change.The imbalance between Th1 and Th2 recurrent spontaneous abortion are an important feature. To explore the same precursor cells divide to different subtypes will help clarify the molecular mechanism of the nature of recurrent spontaneous abortion. Extracellular signaling molecules, intracellular signaling, nuclear transcription factor-control aspect of the three T cell differentiation, including transcription factor T-bet, GATA-3, extracellular signaling molecules IL-12, IL-4 and intracellular signaling molecule STAT4, STAT6 plays a key role.Th1 and Th2 cells are from a common naive precursor cells from. What mechanisms cause the same precursor cells divide to different types of people attracted great interest, making the impact of T cell differentiation factors and intracellular signal transduction pathway has become the research hot spots. Therefore, to explore the mechanism of T cell differentiation clear recurrent spontaneous abortion for the pathogenesis and to explore new intervention on the treatment aspect of great significance。Th2 differentiation, connected with the extracellular cytokine transcription factor Th differentiation between the intracellular signal transduction, differentiation induced by Th2 cytokines are the key IL-4, it is to play a role through the STAT6. Th1 differentiation induced by cytokines are the key IL-12, it is through the role of STAT4.Signal transducer and activator of transcription factor are a class of hidden in the cytoplasm, can be a large number of activated extracellular peptide molecules involved in regulation of gene transcription protein family. STAT6 is a member of the family, through the JAK-STAT signal transduction pathway mediated by cytokines IL-4, IL-13 gene expression, etc., play a variety of biological functions. When IL-4 with the membrane receptor (IL-4Rα) effect, caused by tyrosine System (JAKs) activation, and activation of cytoplasmic STAT6, caused by the Y641 site on protein tyrosine phosphorylation of residues, activation of the SH2 region homologous or heterologous dimerization and the formation of dimers; dimer into the nucleus with a specific DNA binding sites, caused by IL-4 gene expression. STAT6 activation of a variety of biological functions, including regulation of TH2 response, such as advantages in the pathogenesis of RSA play an important role. STAT4 gene located on chromosome 2q32.2-q32.3, it is the regulation of IL-12 and T cell differentiation of the essential factors, previous studies have shown that IL-12 mediated activation of STAT family, through the activation of STAT4 after IL-12 of the signaling pathway regulating Th1 cell differentiation, if the decline in the expression of STAT4, will significantly inhibited IL-12-mediated Th1 response. IL-12 knockout or TH1 cells STAT4 cause a significant reduction in the response, IFN-γinduction of Th1 response mainly inhibit IL-4-mediated Th2 response, in the pathogenesis of RSA play an important role in same.STAT4,STAT6 and Th1,Th1 closely related to the balance , Can be induced STAT4 activation and Th1 polarization of a series of genes, the experiment found that wild-type and STAT4-deficient mice demonstrated the advantages Th2 immune response, STAT6-deficient mice show Th1 immune advantage through STAT4 cytokine regulation of immune cells to Th1 differentiation The most important signal transduction pathways, and STAT6 through cytokine regulation of immune cells to the Th2 differentiation of the most important signal transduction pathway.The use of our method of imrnunohistochemistry in patients with RSA decidual and villous tissues of STAT4, STAT6 expression method provides a basis for study. STAT6 and STAT4 and Th1, Th2 study the relationship between the more RSA patients in the decidua and chorionic villi tissues whether such a relationship exist? The expression of STAT4 and STAT6 with RSA on the Change? Whether or not there is correlation between the two? Home has not been reported.Purpose 1. Research RSA patients decidual and villous tissues the expression of STAT4 and STAT6. Explore the decidual and villous STAT6 and STAT4 and Th1, Th2, as well as in the decidua of patients with RSA, the relevance of villi.2. STAT4 and STAT6 signal transduction pathway from the aspects of the pathogenesis of RSA into fields of study.Materials and methods1.①RSA study group Choice 2007年11 to 2008 in the 5 month treatment Third Affiliated Hospital of Zhengzhou University gynecology outpatient visit within 12 weeks of pregnancy Qinggong URSA patients 20 cases of patients, aged 26-35 years old, average 29-year-old, natural Abortion number≥2, the B-prompt cessation of embryonic development. Exclude chromosomal, anatomical, endocrine, and infections, autoimmune diseases.②normal pregnancy group: select the same period of treatment in our hospital out-patient gynecology, pregnancy within 12 weeks of the normal requirements of the early abortion 20 cases of pregnant women, aged 24～35 years old, average 28-year-old; past without spontaneous abortion, stillbirth, stillbirth history No chromosomal, anatomical, endocrine abnormalities and infection area, the history of autoimmune diseases, there is one child more than the history of normal birth, this pregnancy without vaginal bleeding, abdominal pain and other symptoms and signs of threatened abortion; B ultrasonography confirmed normal embryonic development.2. Ways to collect two sets of maternal decidua and villus fresh, with 10% neutral formalin-fixed, paraffin-embedded. By immunohistochemistry for qualitative and semi-quantitative measurement of decidual and villous tissues of STAT4 and STAT6 expression.3. All data were statistically analyzed using statistical analysis SPSS10.0 software. A = 0.05 as there is no significant difference test. Results1. Study the general situation is: RSA group and the control group, gestational age and there was no significant difference (p> 0.01).2. STAT4 villi in the two tissues: STAT4 in the two groups showed a positive expression of villi, the main expression in the cytoplasm of trophoblast cells. Higher than the expression level of RSA group. (P <0.01)3. STAT4 in the two decidual tissues: The expression of quality in the middle of decidual cells. STAT4 in the two decidual tissues lower than the same group villi (p4. STAT6 villi in the two tissues: STAT6 main expression in the cytoplasm of trophoblast cells. The expression level of the control group than the RSA group. (P5. STAT6 in the two decidual tissues: The expression in the middle of decidual stromal cells. STAT6 in the two decidual tissues lower than the same group villi (p6. RSA group of maternal-fetal interface of STAT4 and STAT6 expression level was negatively correlated. (R =- 0.789, P <0.01)Conclusion1. RSA Group villi and decidua in STAT4 expression, STAT6 decreased expression may be related to the occurrence of RSA.2. RSA group on maternal-fetal interface of STAT4 and STAT6 expression level was negatively correlated, suggesting possible synergy between the two cause the occurrence of RSA in order to further study the molecular pathogenesis of RSA to provide a basis.