FADD,Livin In The Missed Abortion Villi Tissue Expression And Its Significance

Background and ObjectiveMissed abortion is a special case of abortion, refers to an embryo or fetus died stranded intrauterine failed to natural discharges. If the dead materials in intrauterine pregnancy stay too long, they can cause severe coagulation dysfunction. Intrauterine fetal death and retention is easy to adhersed with uterine muscle wall, and they can not be cleared easily. The reason for missed abortion is not clear. This study was detected two materials expression in missed abortion tissues:Fas-associated protein with death domain (FADD) and Livin (a member of the inhibitor of apoptosis proteins family, IAPs). To explore the relationships of FADD, Livin and missed abortion.FADD was cloned by Chinnaiyan, etal. It is a Fas-induced apoptosis protein and a critical signal transduction factor in the apoptosis pathway. FADD is recongnized as apoptosis gene in the human 11q13.3.Its main pathway:Fas triggers apoptosis through FADD, and caspase-8 is raised and activated. After the effects of the Fas system, FADD protein moves to the plasma membrane. FADD's death domain of Fas death receptor DD bines the DD part of integration, then FADD bines with the caspase-8 precursors of the death effector domain (DED). Active Caspase-8 precursor is released from the DISC, then other effectors caspase (caspase-3\cspase-6\caspase-7, etal) are cleavaged and activated. Lastly the caspase cascade is activated, and cells apoptosis occurs. After Pairs of FADD in-depth studys, FADD plays impotant role not only in apoptosis signal transduction pathway, but also in embryonic development and immune system.Livin was found in 2000, it belongs to inhibitor of apoptosis proteins (inhibitor of apoptosis protein, IAP) family. It is a new member of BIR proteins family structure and IAPs play a critical role in anti-apoptosis. BIR domains can bind with caspase enzymes. Livin can blockd apaptosis induced by FADD, etal. It blocks apoptosis receptors and the mitochondriabased apoptotic pathway by inhibiting caspase activity, especially caspase-3/-7 and caspase-9.Current research shows that Livin expresses in variety of organizations of fetal development, such as the fetal brain, thymus, placenta, kidney and liver, while no expression in normal adult organizations (except the placenta). Hakhyun uses RT-PCR technique to detect Livin mRNA in placental trophoblast cells to express. They found that expressed mainly in the chorionic trophoblast cells of the cytoplasm. It played a regulatory role in embryonic development.Using RT-PCR method and SP immunohistochemistry, To detect the expressions of FADD and Livin in missed abortion and normal pregnancy chorionic villi. Analysis their relationships, and the correlation with missed abortion, further to reveal the possible missed abortion molecular pathogenesis.Materials and Methods1 Clinical cases dateSamples take from July 2008 to November 2008 in the First Affiliated Hospital of Zhengzhou University and the Third Affiliated Hospital of Zhengzhou University, Obstetrics and Gynecology.30 patients with missed abortion are research objects (experimental group). Missed abortion diagnostic criteria are referenced from the seventh edition textbook to obstetrics and gynecology. Compared group are 30 patients requested termination of pregnancy. All the subjects have no pregnancy complications or infectious diseases. They have normal menstruation.The former did not use any steroid hormone drugs. Two groups of pregnant women's age and the number of days of pregnancy have no statistically significant differences.They are all early abortions (gestational age<12weeks), with an average age of 27.6 years (23-37years).2 Experimental methodsFADDmRNA and LivinmRNA was detected of the placental villi in patients with normal pregnancy and missed abortion using RT-PCR method. Livin protein and' FADD protein were detected in the placental villi of patients with normal pregnancy and missed abortion by immunohistochemical.3 Statistical analysisAll datas are analysised by SPSS13.0 statistical software. Analysis of attribute dates comparison used contingency table chi-square test and Fisher's exact test.The statistical methods of measurement dates used the t-test. The test standard wasα=0.05ResultsImmunohistochemistry results:FADD protein in missed abortion group Chorion positive rate was 86.67%(26/30),60.0%(18/30) in normal chorionic villi. The difference was significant. (χ2=5.455, P=0.020). Livin protein in missed abortion villi, the positive rate was 63.33%(19/30), and 90.0%(27/30) in normal villi. The difference was significant (χ2=5.963, P=0.015)RT-PCR results:In missed abortion group villi FADD mRNA expression is higher than the normal pregnancy group, (t=7.220, P=0.002). And the missed abortion group Livin mRNA expression villi was lower than the normal group (t=10.661,P=0.000).FADD and Livin in the missed abortion group placenta expression has no correlation.Conclusions 1 FADD protein and FADDmRNA in villi of the missed abortion group was significantly higher than in normal pregnancy group. FADD may play a role in the development of missed abortion.2 Livin protein and Livin mRNA in villi of missed abortion group was significantly lower in early pregnancy. This indicated that low expression of Livin may have close relationship with missed abortion. 3 FADD in missed abortion placenta and the high expression of Livin in the missed abortion placenta low expression may involve in the occurrence and development of missed abortion. The two factors are probably expected as new entry points in missed abortion prevention, gene diagnosis and treatment.