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Etiological Analysis Of Recurrent Spontaneous Abortion And The Research With Abnormal Expression Of Chemokines CXCL12, CCL2, RANTES

Posted on:2011-12-31Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y ZhangFull Text:PDF
GTID:1114360308968219Subject:Obstetrics and gynecology
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Recurrent spontaneous miscarriage(RSA) is loss of two or more consecutive pregnancies. It is experienced by 5% of couples. The etiology of RSA is complicated, 50% of cases of RSA is unknown, which is called URSA.Part 1 The etiological factors of RSA.Objective To analyze etiological factors of RSA.Methods 74 RSA couples were selected and scanned systematically for analyzing etiological factors.Results 74 RSA couples,6 cases with abnormal chromosomes(8.1%),4 cases with uterine malformation(5.4%); 13 cases with abnormal hormones(17.6%); 5 cases with reproductive infection(6.8%); 46 cases with immunological factors(62.1%), including 14 cases with positive self-antibodies(18.9%) and 32 cases with unknown aetiology(43.2%).Conclusion The etiology of RSA is complicated, including genetic factors, endocrine factors, uterine malformation, infective and immunological factors. RSA is mainly related to immunological factors.Part 2:Roles of CXCL12, CCL2, RANTES in pathogenesis of URSAObjective To investigate the abnormal expression of CXCL12,CCL2,RANTES mRNA in villus and decidua and serum levels of CXCL12, CCL2, RANTES in URSA patients in order to find out its association with the pathogenesis of URSA.Methods The expression of CXCL12, CCL2, RANTESmRNA in villus and decidua tissues of 26 URSA patients(URSA group)and 30 normal early pregnancy women(control group) were determined by real-time fluorescence quantitative PCR. the maternal serum levels of CXCL12, CCL2, RANTES were detected by ELISA.Results 1) CXCL12,CCL2,RANTESmRNA expression were detected in human first-trimester placental villus and decidua tissues; 2) The expression of CXCL12mRNA in villus and decidua in URSA group were (0.46±0.15,0.35±0.13), which was lower than that in control group(1.79±0.82,0.81±0.21)(P<0.01); CCL2mRNA were (1.99±0.35,2.77±0.61), which was higher than that in control group(1.42±0.28,1.90±0.85) (P<0.01); RANTESmRNA were (1.40±0.25,2.25±0.33), which was higher than that in control group(0.94±0.22,1.45±0.20)(P<0.01).3) The level of serum CXCL12 in URSA group was (194.52±29.23pg/ml), which was lower than control group(268.13±26.36pg/ml)(P<0.01); CCL2 was (83.34±10.61pg/ml), which was higher than control group (59.41±9.70pg/ml)(P<0.01); RANTES was (117.29±18.67pg/ml), which was higher than that in control group(79.88±12.54pg/ml) (P<0.01).4)The serum CXCL12 levels were positively correlated with CXCL12mRNA levels in villus and decidua (r=0.723,0.604 respectively)(P<0.01); CCL2 levels were positively correlated with CCL2 mRNA levels (r=0.595,0.655 respectively)(P<0.01); RANTES levels were positively correlated with RANTES mRNA levels in both groups(r=0.482,0.675 respectively) (P<0.01).Conclusion CXCL12,CCL2,RANTES were co-expressed in human villus and decidua, they contribute to the trophoblast invasion and deciduous cell constitution at matemo-fetal interface; the lower CXCL12 expression and higher CCL2, RANTES expression play important roles in the pathogenesis of URSA; the levels of serum CXCL12, CCL2, RANTES can be used as a tool for diagnosing embryonic death.Part 3:Effect of mifepristone on the expression of chemokines CXCL12, CCL2, RANTES in villus and decidua of early pregnancyObjective To investigate mifepristone on the expression of CXCL12,CCL2,RANTES in villus and decidua of early pregnancy.Methods The expression of CXCL12, CCL2, RANTESmRNA in villous and deciduous tissues of 30 normal early pregnancy women who volunteered to take mifepristone (mifepristone group) were determined by real-time PCR.Results The expression of CXCL12 in mifepristone group were (0.59±0.22, 0.42±0.17), which was lower than control group(P<0.01); CCL2 were(1.84±0.35, 3.01±0.62), which was higher than control group(P<0.01); RANTES were(1.33±0.22; 2.17±0.49), which was higher than that in control group(P<0.01).Conclusion Mifepristone affect the expression of chemokines and induce the disorder of micro-enviromnenl, which might be the mechanism of medical abortion.
Keywords/Search Tags:Recurrent sponneous abortion, Chemokines, CXCL12, CCL2, RANTES, Mifepristone, Matemo-fetal interface, Immune tolerance
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