Populational change of CD4^(+)CD25^(+)Treg cells is responsible for the synergistic effect of the combination of RAMP2 with baicalin in treating recurrent spontaneous abortion mouse models

Background: The absence of a safe and effective therapy for recurrent spontaneous abortion due to a maternofetal failure in immunological tolerance remains an intractable clinical obstacle for surgeons. Recently, traditional Chinese medicine has become a feasible alternative for certain diseases, including recurrent spontaneous abortion. However, because of the complex composition of the traditional Chinese medicine formula, its action mechanism remains unclear. Methods: We selected two isolated active ingredients (RAMP and baicalin) from the traditional Chinese medicine formula and used an abortion-prone CBA/J × DBA/2 model to simulate human RSA and compared the changes in fetal resorption rate, Treg cell percentage, and relevant cytokines before and after combination therapy. In addition, The mechanisms were preliminarily discussed using in vitro differentiation models. Results: In CBA/J × DBA/2 abortion-prone mice, the combination therapy resulted in a lower embryo resorption rate compared to that obtained with individual delivery of either RAMP or baicalin, thereby playing an embryo-protective role through the increase in Treg cells for the maintenance of maternal-fetal immune tolerance. In in vitro primary cell differentiation experiments, the concentration of Treg cells significantly increased from 11% to 17.9% after the combination therapy compared to that of the single administration group. Conclusion: the synergistic effects of RAMP and baicalin were responsible for Treg differentiation. The present study provides a solid basis for improving the applicability of traditional Chinese herbs in the treatment of recurrent spontaneous abortion.

Increase of tumor necrosis factor receptor 1 expression in women with unexplained early spontaneous abortion

Objective: To investigate membrane tumor necrosis factor receptor 1 protein expression level in decidua and concentration of soluble tumor necrosis factor receptor 1 in serum in women with unexplained early spontaneous abortion, threatened abortion, and compare the levels with healthy pregnant women. Methods: Thirty-seven women with unexplained early spontaneous abortion, 27 women with threatened abortion, and 34 healthy pregnant women undergoing artificial abortion of pregnancy at 6 - 10 weeks of gestation were selected. Decidual samples were collected when women were undergoing artificial abortion, and blood samples were collected at the same time. The level of membrane tumor necrosis factor receptor 1 in decidua was detected by flow cytometer, and the concentration of soluble tumor necrosis factor receptor 1 in sera was measured with an enzyme-linked immunosorbent assay. Results: The percentages of membrane tumor necrosis factor receptor 1 positive decidual cells were 16.42 ± 7.10 Mean ± SD for women with unexplained early spontaneous abortion and 13. 14 ± 6.30 for healthy pregnant women ( P < 0.05). Serum concentration of soluble tumor necrosis factor receptor 1 was significantly higher in women with unexplained early spontaneous abortion than in healthy pregnant women and in women with threatened abortion, and no difference was found between healthy pregnant women and women with threatened abortion. Conclusion: Women with unexplained early spontaneous abortion present significantly higher expression of tumor necrosis factor receptor 1 than healthy pregnant women, suggesting that over-expression of tumor necrosis factor receptor 1 may contribute to the development of early spontaneous abortion.

Up-regulated Expression of Tim-3/Gal-9 at Maternal-fetal Interface in Pregnant Woman with Recurrent Spontaneous Abortion

The relationship between T cell immunoglobulin domain and mucin domain protein 3（Tim-3）/Galectin（Gal）-9 pathway and recurrent spontaneous abortion（RSA） was studied. Thirty-one pregnant women with RSA and 27 normal early gravidas were investigated to detect the levels of Tim-3 and Gal-9 in villi and deciduas by Western blotting. Meanwhile, the concentration of interleukin（IL）-4 and IL-12 in peripheral blood plasma was determined by ELISA in 25 healthy fertile non-pregnant controls, the normal early gravidas and pregnant women with RSA mentioned above, respectively. It was found that the relative expression levels of Tim-3 and Gal-9 in villi and deciduas were significantly increased in pregnant women with RSA as compared with those in the normal early gravidas. The concentration of IL-4 in peripheral blood plasma of pregnant women with RSA was lower than that of the normal early gravidas（P〈0.05） and healthy fertile non-pregnant controls（P〈0.05）, but that of IL-2 in pregnant women with RSA was significantly higher than that of the normal early gravidas（P〈0.05） and healthy fertile non-pregnant controls（P〈0.05）. It was suggested that the overexpression of Tim-3/Gal-9 pathway may be related to the pathogenesis of RSA.

The Effect of Lymphocyte Immunotherapy on CD80^+ Cells at the Fetomaternal Interface and Cyesis Result of Mice Model of Spontaneous Abortion

Objectives To explore the relationship between CD80 expression on lymphocytes at the fetomaternal interface and the fertility characteristics in CBA/J×DBA/2 mice as a model of recurrent spontaneous abortion (RSA) and to investigate the effects of lymphocyte immunotherapy (LIT) on the level of CD80 expression. Materials & Methods The characteristics of fertility in CBA/J×DBA/2 mice were observed in a 120 day period and compared with four normal fertile groups. In another 15 pairs of CBA/J×DBA/2 breedings, resorption rate on day 13 of pregnancy were calculated and the proportion of CD80 + cells at the fetomaternal interface were determined by using two color flow cytometric analysis, mainly stained with CD80 FITC and CD45 PE. In order to determine the identity of CD80 + cells, the expression levels of CD3(T cell marker), DX5(NK cell marker), and MHC II(antigen presenting cell marker) were detected in this cell population. Furthermore, the resorption rate and the proportion of CD80 + cells among CBA/J×DBA/2 breedings with and without immunotherapy were also determined and compared with normal fertile controls. Results The characteristics of abortion in CBA/J×DBA/2 mice were recurrent abortion on about day 10 of gestation. The resorption rate in CBA/J×DBA/2 mice was significantly higher than that in BALB/c×DBA/2 mice (30.8%±16.6% vs. 7.7%±6.7%, P<0.01). Accordingly, the proportion of CD80 + cells evaluated at the fetomaternal interface in CBA/J×DBA/2 mice was also significantly higher (11.7% ±5.8% vs. 3.9%±1.8%, P<0.01). Resorption rate of CBA/J×DBA/2 mice underwent of LIT was significantly lower than that without LIT, and this decreased rate was correlated with decreased proportion of CD80 + cells. Conclusion In CBA/J×DBA/2 mice model, the characteristics of abortion seem to be peri implantation embryo resorption. A correlation between early embryonic waste and higher CD80 proportion at the fetomaternal interface suggests that CD80 + cells may be an important determinant in recurrent peri implantation abortion.

Research advances of Chinese and Western medicine in the treatment of unexplained recurrent spontaneous abortion

Recurrent spontaneous abortion is a common disease in gynecology,and it seriously affects women's reproductive health and brings heavy burden and pain to society and families.The cause of recurrent spontaneous abortion is complicated,in addition to the well-defined genetic,anatomical,infection and endocrine factors,and there are still some unknown causes,which is called as unexplained recurrent spontaneous abortion,accounting for 40%of recurrent abortion.At present,there are a lot of researches on the treatment methods of the patients with the unexplained recurrent spontaneous abortion,which also shows that the treatment of traditional Chinese and Western medicine all have certain clinical application effect.Western medicine clinical methods mainly includes immunotherapy,immunosuppressive therapy,anticoagulation therapy,progesterone therapy,etc.Based on the experience of the professor and combined with many years of clinical practice,the author believes that the pathogenesis of this disease in traditional Chinese medicine is mainly due to impaired impulse and deficiency of Spleen,lack of qi and blood,can not nourishing the fetus;deficiency of Kidney Qi,blood flow was delayed,and blood stasis and could not raise the fetus.Clinical treatment is based on invigorating the kidney,tonifying spleen and nourishing blood,promoting blood circulation to remove blood stasis and dredging collaterals.Oral Chinese medicine combined with external acupuncture and moxibustion has achieved excellent effects in improving pregnancy rate.This article reviews the domestic and foreign methods of treating unexplained recurrent miscarriage in order to provide clinical reference.In the future,the combination of Chinese and Western medicine should become the main therapy to increase pregnancy rate.

Expression of AIF-1 and RANTES in Unexplained Spontaneous Abortion and Possible Association with Alloimmune Abortion

Objective To investigate the effects of allograft inflammatory factor-1 （AIF-1） and （RANTES） in sera and deciduas on unexplained early spontaneous abortion. Methods AIF-1 and RANTES were examined in sera and deciduas/endometria of 43 unexplained early spontaneous abortion women （group A）, 40 healthy women with early pregnancy（group B） and 20 healthy women with no pregnancy （group C）. Immunohistochemistry and enzyme linked immunosorbent assay （ELISA） were used in this study. Results AIF-1 protein was expressed both in deciduas of group A and in endometria of group C. In group A, H scores in the recurrent abortion deciduas specimens were significantly greater than those in the first abortion;in endometrium, expression of AIF-1 was greater in the secretory than in proliferative phase of group C. In group B, concentrations of RANTES in sera were higher in 7th-8th week of pregnancy than in 6th-7th and 〉8th week of pregnancy; expression of AIF-1 protein showed a negative correlation with RASNTES concentration; a significant increase of the RANTES levels in sera and tissue was observed in group B. Conclusion These results demonstrate, for the first time, that AIF-1 are expressed in deciduas of unexplained spontaneous abortion suggesting that AIF-1 involve in alloimmune abortion; RANTES might act as a novel blocking antibody;AIF-1 and RANTES might act as reliable markers for diagnosis of early alloimmune abortion.

Meta-Analysis of Bushen Huoxue Method in the Treatment of Recurrent Spontaneous Abortion Due to Prethrombotic State

Objective:To evaluate the effectiveness and safety of Bushen Huoxue prescription in the treatment of recurrent spontaneous abortion(RSA)due to prethrombotic state(PTS).Methods:Databases such as CNKI,WanFang,VIP,CBM,PubMed,Embase,and Cochrane Library were searched for randomized controlled trials on Bushen Huoxue prescription in treating RSA due to PTS from inception to March 2021;meta-analysis was performed by RevMan Version 5.3.0 following quality evaluation.Results:Seven trials were included,with 496 patients;the meta-analysis indicated that Bushen Huoxue prescription has advantages on the improvement of total clinical effective rate[RR=1.22,95%CI(1.10,1.35),Z=3.80(P=0.0001)],embryo survival rate at pregnancy of 12 weeks[RR=1.25,95%CI(1.10,1.41),Z=3.53(P=0.0004)],D-dimer levels[SMD=-1.59,95%CI(-2.20,-0.97),Z=5.07(P<0.00001)],and fibrinogen levels[MD=-1.00,95%CI(-1.29,-0.70),Z=6.61(P<0.00001)],but the statistical heterogeneity was significant;in terms of incidence of adverse reactions,there was no statistical difference between Bushen Huoxue prescription and western medicine.Conclusion:Compared with western medicine alone,Bushen Huoxue prescription alone or in combination with western medicine showed significant advantages in improving the overall clinical efficiency,embryonic survival rate at 12 weeks of pregnancy,and reducing D-dimer values as well as fibrinogen levels,without any significant difference in the incidence of adverse effects;however,the number of included studies is small and there are drawbacks,such as small sample size and low quality;therefore,high-quality clinical studies with large sample size and rigorous trial designs are needed in the future to provide a reliable basis for the effectiveness and safety of TCM in reducing the incidence of RSA due to prethrombotic state.

Correlation of BDNF Gene Polymorphism and Psychological Nursing Intervention in Patients with Recurrent Spontaneous Abortion

Objective: To investigate the correlation between recurrent spontaneous abortion patients and brain derived neurotrophic factor BDNF gene polymorphism and the mechanism of BDNF and recurrent spontaneous abortion under stress state in order to provide theoretical basis for nursing psychological intervention of patients with recurrent abortion. Methods: Medical coping Questionnaire (MCMO) and post-traumatic stress Diagnostic Scale (POST-traumatic stress Scale) were adopted Dissorder (PTSD) (PCL-c) scale was used to diagnose the psychological stress of recurrent spontaneous abortion in our hospital, and the BDNF gene polymorphism and the correlation factors of METHYLation in BDNF promoter region were studied in 30 cases (control group) and normal control group. Results: The MCMQ score of the case group and the control group was significantly lower than that of the conventional group (P Conclusion: There are significant differences in PTSD between the case group and the control group, which are related to methylation in the PROMOTER region of BDNF and SNP g-712A of BDNF gene. AG patients in the case group are more susceptible to anxiety and depression, and GG PTSD is more severe in the case group. BDNF promoter methylation and G-712A were independent risk factors for PTSD in the case group.

Small RNA sequencing revealed aberrant piRNA expression profiles in deciduas of recurrent spontaneous abortion patients

Piwi-interacting RNAs(piRNAs)is a novel class of non-coding RNAs.However,changes in piRNA expression profiles in recurrent spontaneous abortion(RSA)have not yet been investigated.The aim of this study was to identify differentially expressed piRNAs in deciduas of RSA patients.Decidua tissues were collected by curettage from recruited RSA patients and normal early pregnant(NEP)women with their informed consent.Small RNA sequencing was used to evaluate the differences in piRNA expression profiles between RSA and NEP.The present results demonstrated that the counts of total piRNA reads in RSA samples were increased compared with those in NEP samples(0.21%vs.0.11%).Differential expression analysis identified 29 upregulated piRNAs and 18 downregulated piRNAs in RSA samples.RT-qPCR further confirmed that the expression levels of uniq-109625,uniq-89328,uniq-50651 and uniq-4569 were decreased in 8 RSA tissues,compared with 13 NEP tissues.Otherwise,pi-22628 and uniq-173406 were increased in 8 RSA tissues.Based on GO term and KEGG pathway analysis,we speculate that these piRNAs regulate RSA by targeting extracellular matrix component pathway,cell adhesion pathway and focal adhesion pathway.PiRNAs may be involved in RSA pathogenesis by target genes function on adhesion and extracellular matrix component.

Investigation of FOXP3 (rs3761548) polymorphism with the risk of preeclampsia and recurrent spontaneous abortion: A systemic review and meta-analysis

Objective:To investigate the association between forkhead box P3(FOXP3)(rs3761548)polymorphism and the risk of preeclampsia and recurrent spontaneous abortion.Methods:Literature on the association of FOXP3 gene polymorphisms and susceptibility to preeclampsia and unexplained recurrent spontaneous abortion was retrieved by searching databases such as PubMed,Science Direct,Google Scholar and Embase from 2000 to 2021.The association measure was analyzed using an odds ratio(OR)and 95%confidence interval(CI).All the statistical analyses were executed using RevMan 5.4 software.Results:In the present meta-analysis,11 articles were analyzed.The pooled results showed no association between FOXP3 gene polymorphism(rs3761548)and preeclampsia risk in allelic,recessive,dominant and over dominant contrast models.FOXP3 gene polymorphism(rs3761548)showed an association with recurrent abortion in allelic,recessive and dominant models(OR 1.85,CI 1.59-2.14;OR 2.02,95%CI 1.56-2.62;OR 2.69,95%CI 1.50-4.83,respectively),while no association in the over dominant contrast model(OR 1.35,CI 0.87-2.10).Conclusions:In the present study,FOXP3 gene(rs3761548)polymorphism is associated with risk of recurrent spontaneous abortion but not preeclampsia.However,larger sample size and multiracial studies are needed in the future to confirm the findings.

Association between p53 Polymorphism at Codon 72 and Recurrent Spontaneous Abortion

p53 gene plays an important role in apoptosis, which is necessary for successful invasion of trophoblast cells. The change from an arginine（Arg） to a proline（Pro） at codon 72 can influence the biological activity of p53, which predisposes to an increased risk of recurrent spontaneous abortion（RSA）. In order to investigate the association between p53 polymorphism at codon 72 and RSA, we conducted this meta-analysis. Pubmed, Embase and Web of science were used to identify the eligible studies. Odds ratio（OR） with 95% confidence interval（CI） was used to evaluate the strength of the association. Six studies containing 937 cases of RSA and 830 controls were included, and there was one study deviated from Hardy-Weinberg equilibrium（HWE）. There was a significant association between p53 polymorphism at codon 72 and RSA in recessive model（Pro/Pro vs. Pro/Arg＋Arg/Arg; OR=1.60, 95% CI： 1.14–2.24） and co-dominant model（Pro/Pro vs. Arg/Arg; OR=1.47, 95% CI： 1.02–2.12） whether the study that was deviated from HWE was eliminated or not. A significant association was observed in allelic model（Pro vs. Arg; OR=1.28, 95% CI： 1.04–1.57） after exclusion of the study that was deviated from HWE. No association was noted in recessive model（Pro/Pro＋Pro/Arg vs. Arg/Arg; OR=1.05, 95% CI： 0.86–1.30） and co-dominant model（Pro/Arg vs. Arg/Arg; OR=0.96, 95% CI： 0.77–1.19）. Subgroup analysis by ethnicity also indicated a significant association between p53 polymorphism at codon 72 and RSA in Caucasian group. No heterogeneity and publication bias were found. Our meta-analysis implied that p53 polymorphism at codon 72 carries high maternal risk of RSA.

Advances of Genetic Testing Technology in Etiology Diagnosis of Recurrent Spontaneous Abortion

Recurrent spontaneous abortion (RSA) is a complex and heterogeneous disorder with multiple etiologies. Genetic factors are thought to play an important role in the etiology of RSA. With recent advances in genetic testing technologies, there has been an increasing interest in using these tools to diagnose the etiology of RSA. This review discusses the different types of genetic testing methods, such as karyotyping, chromosomal microarray analysis, next-generation sequencing, and their applications in the diagnosis of the etiology RSA. The use of genetic testing in the diagnosis of RSA has the potential to improve the accuracy of diagnosis and the understanding of the underlying mechanisms of the disorder, which could lead to better management and treatment of affected individuals.

Animal study on CD4^(+) CD25^(+) regulatory T cells for treating female mouse with recurrent spontaneous abortion

Objective:To explore immunotherapy effectiveness of the CD4^(+)CD25^(+) regulatory T cells for treating female mouse with recurrent spontaneous abortion(RSA)by animal experiments.Methods:Mononuclear lymphocytes were isolated from the blood(instead of cord blood)of new-born baby of KunMing Bai mouse or BALB/c male mouse with normal birth ability(as unrelated third party blood source)by density gradient centrifuga-tion method.The CD4^(+)CD25^(+) regulatory T cells were selected by magnetic-activated cell sorting from mononuclear cells of cord blood cells.CBA/J female mouse copulated with DBA/2J male mouse was utilized as RSA animal model.Pregnant RSA mice were injected different types of lymphocytes through tail vein.Independent sample t-test was used to analyze the data from each group.Results:The proportion of CD4^(+)CD25^(+)T cells in CD4^(+)T cells was(17.49±0.60)%in CD4^(+)CD25^(+) regulatory T cells injection group,which was statistical significant higher than that of mononuclear lymphocyte injection group(14.68±0.83)%,sterile PBS group(9.54±0.85)%or no injection group(9.28±0.68)%(p<.05,t-value was 4.754,13.242 and 15.621,respec-tively).The Foxp3 relative protein expression level of CD4^(+)CD25^(+) regulatory T cells injected group was 5.85±0.45,which was also significant higher than that of mononuclear lymphocyte injection(2.86±0.54),sterile PBS group(1.08±0.16)or no injection group(1.00±0.00)(p<.05,t-value was 7.276,17.227 and 18.635,respectively).Finally,two times of CD4^(+)CD25^(+)T cell injected group at the 4 th and 8 th day had well effect for RSA mouse,and embryo sorption rate was(4.92±0.08)%,which significant lower than that of two times of mononuclear lymphocyte injected group(13.07±0.06)%,sterile PBS group(23.11±0.12)%,or no injection group(25.47±0.11)%(p<.05,t-value was-2.603,-4.012 and-4.700,respectively).Conclusions:Pregnant mouse with RSA injected CD4^(+)CD25^(+)T cells several times for immunotherapy can get better effec-tiveness than that of pregnant mouse injected traditional mononuclear cells.

Chinese and Western medicine treatment of blocking antibody in recurrent spontaneous abortion

The causes of recurrent spontaneous abortion are complex traditional Chinese medicine holds that its etiology is losses of spleen and kidney qi, qi and xue deficiency, in addition to secretion, genetic, anatomical, infection, systemic diseases, environmental factors and other related immune factors, the deficiency of blocking antibody is also one of the reasons for the lack of immune factors. In treating it, Chinese medicine treatment combines the patients personal constitution and treatment based on syndrome differentiation; Western medicine treatment mainly applies Aspirin, active immune lymphocyte treatment, low molecular heparin, gamma globulin protein passive immune treatment and psychological intervention therapy. In this paper, a review of the treatment methods for closed antibodies in the past 5 years is made.

Expression of the Inducible Nitric Oxide Synthase Isoform in Chorionic Villi in the Early Spontaneous Abortion

To investigate the relationship between inducible nitric oxide synthase (iNOS) and the early spontaneous abortion. , in situ hybridization and immunohistochemistry were used to detect the expression of iNOS in trophoblasts in the early pregnancy with and without spontaneous abortion (group Ⅰ and group Ⅱ). By light microscopy and computer color magic image analysis system (CMIAS), light density (D) and the positive cell number per statistic square (N/S) in situ hybridiza- tion were used to analyze the positive cell index, while total positive cells (N) and the positive unit (Pu) were used in immunohistochemistry. By in situ hybridization, D and N/S in trophoblasts were 0.35±0. 028, 0. 07±0. 011 respectively in group Ⅰ and 0. 18±0.016,0. 015±0. 003 in group Ⅱ . In terms of immunohistochemical staining, N and Pu were 0. 058±0.007, 11. 94±2. 01 in group Ⅰand 0.013±0.009, 1.08±0. 35 in group Ⅱ in trophoblasts. Significant differences existed between two groups. It is concluded that the higher nitric oxide produced by the higher expression of iNOS in tro- phoblasts might play an important role in the early spontaneous abortion.

Expression of Apoptosis and Inducible Nitric Oxide Synthase in Trophoblastic Cells in Early Spontaneous Abortion

Objective To investigate the effect of apoptosis and inducible nitric oxide (iNOS) on the early spontaneous abortion Methods TUNEL method was used to detect the apoptosis in trophoblast cells in early pregnancy with and without spontaneous abortion (the experiment group and the control group), while iNOS was detected by both in situ hybridization and immunohistochemistry. By computer color magic image analysis system(CMIAS), positive cell indexes were represented by D (density) and N/S(number/square) in both apoptosis and in situ hybridization, in immunohistochemistry were N/S and PU(positive unit). Results Positive cell indexes of apoptosis D and N/S were significntly higher in the experiment group (0.48±0.004, 0.045±0.002) than that in the control group(0.35+0.06, 0.031±0.003. P<0.001). D and N/S of inducible nitric oxide synthase in situ hybridization were 0.33±0.028, 0.074±0.001 respectively in the experiment group and 0.13±0.015, 0.019±0.004 respectively in the control group. N/S and PU were significantly higher in the experiment group(0.058±0.007, 11.94±2.01) than that in the control group (0.007±0.001, 1.18±0.35, P<0.01). There existed a positive correlation between iNOS and apoptosis too. Conclution Apoptosis and iNOS in trophoblasts might play an important role in early spontaneous abortion and there was a positive correlation between apoptosis and iNOS.

EFFECTS OF ANTICOAGULATION PROTEIN DEFECT IN MATERNAL PLASMA ON SPONTANEOUS ABORTION

Objective To investigate the mechanism of anticoagulation protein defect in the pathogenesis of unexplained recurrent miscarriage. Methods Fifty-seven patients with a history of unexplained abortion were enrolled as the investigation group for tests of protein C, protein S, antithrombinⅢ(AT-Ⅲ), as well as activated protein C resistance (APC-R). The control group con-sisted of fifty healthy women with a history of normal pregnancy and delivery. Blood samples were obtained for measuring serum activity of protein C, protein S, AT-Ⅲ, and APC-R. Patients with positive APC-R were tested for factorⅤ(FⅤ) Lei-den gene mutation by PCR-RFLP method. Results Of the 57 patients, 12 (21.1%), 1 (1.8%), and 5 (8.8%) cases were found with protein S, protein C, and AT-Ⅲdeficiency respectively, and 13 (22.8%) cases with positive results of APC-R. Of the control group, no protein C or AT-Ⅲdeficiency was ever found, whereas 2 (4.0%) volunteers were presented with protein S deficiency and 3 (6.0%) with positive results of APC-R. No FⅤLeiden gene mutation was identified in all the patients with positive APC-R results. Late spontan-eous abortion cases had higher incidence of anticoagulation protein defect than the early cases. Conclusion Anticoagulation protein defect may play a role in the pathogenesis of fetal loss, especially for those occurr-ing in late stage of pregnancy.

The Expressions of P53, MDM2 in Trophoblasts of Spontaneous Abortion Mouse Model and the Relevant Researches

Objective: To explore the mRNA expression of the related genes of p53, MDM2, vascular endothelial growth factor (VEGF) and hypoxia inducible transcription factors-1 a (HIF-la) in villous samples of spontaneous abortion mouse models and normal pregnancy models, and to discuss the effect of p53, MDM2 on the growth of villous trophoblast cells. Methods: The abortion-prone CBAXDBA/2 matings were established as the model of spontaneous abortion and the non-abortion-prone CBAXBALB/c matings as the model of normal pregnancy. Applied q Real-time PCR method to detect the mRNA expression levels of p53, MDM2, VEGF and HIF-la in villous samples of spontaneous abortion mouse models and normal pregnancy models. Results: The relationship of the mRNA expression level of p53, MDM2, VEGF and HIF-la in vinous samples of spontaneous abortion mouse models: in the villous samples of spontaneous abortion mouse models, the expression of p53 was positively correlated with the expression of MDM2, HIF-la (r = 0.35;r = 0.63), and the relationship was significant (P = 0.01;P < 0.001);but negatively correlated to the expression of VEGF (r = ?0.30), and the relationship was significant (P = 0.03). The expression of MDM2 was positively correlated with the expression of HIF-la (r = 0.28), and the relationship was significant (P = 0.04);and negatively correlated with the expression of VEGF (r = ?0.08), but the relationship was not significant (P = 0.57). The expression of HIF-la was negatively correlated with the expression of VEGF (r = ?0.37), and the relationship was significant (P = 0.007). The relationship of the mRNA expression level of p53,MDM2, VEGF and HIF-1 a in vinous samples of normal pregnancy models: in the vinous samples of normal pregnancy models, the expression of p53 was positively correlated with the expression of MDM2, VEGF and HIF-la (r = 0. 31;r = 0. 48;r = 0. 67), and the relationship was significant (P = 0.03;P = 0.003;P < 0.001). The expression of MDM2 was positively correlated with the expression of VEGF (r = 0. 23), but the relationship was not significant (P = 0.11);and negatively correlated with the expression of HIF-la (r = ?0.03), but the relationship was not significant (P = 0.84). The expression of HIF-la was positively correlated with the expression of VEGF (r = 0. 35), and the relationship was significant (P = 0.01). Conclusion: angiogenesis reduces in villous samples of spontaneous abortion mouse model, P53 and MDM2 involve in angiogenesis in villous samples, unlikely p53, and MDM2 have effects on normal early pregnancy villous angiogenesis and when the cell DNA damages or hypoxia exacerbates, it can induce high expression of p53, MDM2, inhibit angiogenesis in villous samples in early pregnancy. P53, MDM2 generegulate villous trophoblast cell growth by adjusting expression of HIF-1a and VEGF gene, finally influences pregnancy.

Relationship between the Abnormal Expression of FasL on Human First Trimester Trophoblast and Spontaneous Abortion

In order to study the molecular immune-pathological mechanism of spontaneous abortion (SA), immunohistochemistry techniques were used to detect the FasL expression of first trimester trophoblast in the SA patients and normal controls. High precise color-image measure system for immuno-histochemistry (HPIS) was used to determine the quantity of FasL expression. The results showed that the scale and intensity of FasL expression on the trophoblasts in SA group were significantly lower than in the control group. It is indicated that abnormal expression of FasL on trophoblasts, which damages the immunological tolerance between mother and fetus, may be one of the important mechanisms of development of SA. To induce the expression of FasL or to regulate the immunological tolerance will be a new way to treat SA.