Decidual Natural Killer Cytotoxicity Decreased in Normal Pregnancy but Not in Anembryonic Pregnancy and Recurrent Spontaneous Abortion

PROBLEM : The natural killer (NK) cell activity is depressed in the decidua of early normal pregnancy. Recently Morii et al. (Am J Reprod Immunol 1993;29:1–4) found that all early intradecidual CD3⁺ T cells expressed either T cell receptor (TCR) α/β or γ/δ but that the expression of the CD3⁺/TCR complex was down-regulated. METHOD : To test whether these changes in decidual cellular immunity are different among normal pregnancy, anembryonic pregnancy and recurrent spontaneous abortion, we examined the immune cell subpopulations in the decidua from these three types of pregnancy using flow cytometry and an NK cytotoxicity assay. RESULTS : Intradecidual CD3⁺ T cells expressed either TCR α/β or γ/δ, and the level of expression of the CD3/TCR complex was down-regulated in normal pregnancy, anembryonic pregnancy, and recurrent spontaneous abortion. Although the relative proportion of decidual NK cells was increased to approximately the same extent in all three types of pregnancy, decidual NK activity was higher in anembryonic pregnancies and in recurrent spontaneous abortions than it was in normal pregnancies. CONCLUSION : Decidual NK cell responses are different in anembryonic pregnancies and in recurrent spontaneous abortions than in normal pregnancies. Whether this difference is pathogenic or is the response to a dead embryo remains to be elucidated.     

自然流产中外周血和蜕膜组织自然杀伤细胞亚群的比例变化

目的和方法:采用流式细胞仪检测淋巴细胞亚群法探讨自然流产与正常早孕之间外周血和蜕膜自然杀伤细胞亚群的差异。结果:外周血中自然流产组的CD56⁺的百分率较早孕组有减少的趋势,而CD56⁺CD16⁺的百分率则较早孕组显著减少,CD16⁺的百分率两组间无差异。自然流产组的蜕膜CD56⁺、CD56⁺CD16⁺、CD16⁺的百分率均明显低于早孕组。结论:蜕膜中CD56⁺NK细胞的减少可能是自然流产的原因之一,外周血中CD56⁺和CD56⁺CD16⁺NK细胞的丢失可能对自然流产的发生具有诊断价值。     

Elevated expression of activation molecules by decidual lymphocytes in women suffering spontaneous early pregnancy loss.

The purpose of this study was to investigate, quantify and compare the expression of activation markers by decidual leukocytes in sporadic spontaneous early pregnancy loss and apparently normal first trimester human pregnancy. Decidua was obtained from 18 therapeutic abortions and 20 sporadic spontaneous abortions at 8-12 weeks gestational age. Cryostat sections were labelled by the avidin-biotin complex-peroxidase method using monoclonal antibodies specific for CD45, CD56, CD3, human leukocyte antigen (HLA) DR, CD69, CD25 and very late antigen (VLA)1. Positive cells were quantified and the results were analysed using the Mann-Whitney statistical test. Significantly increased numbers of CD69-positive and CD25-positive cells were detected in spontaneous abortion decidua, when compared with therapeutic abortion decidua. Approximately 50% of women experiencing spontaneous miscarriage also contained significantly elevated numbers of HLA DR-positive cells within decidua. Double immunohistochemical labelling studies demonstrated that the CD25-positive and CD69-positive cells in spontaneous abortion decidua were CD3-positive T cells rather than CD56-positive granulated lymphocytes. Immunological dysfunction within endometrium may account for a proportion of sporadic spontaneous abortions.     

早期不明原因反复自然流产发生与蜕膜中免疫细胞的研究进展

人类妊娠被认为是一种半同种异体抗原移植，母胎间存在着某种免疫耐受机制来维持妊娠的进行，但目前为止这种免疫耐受机制尚不明确。大量的研究发现不明原因反复自然流产患者蜕膜中调节性T细胞的数量和功能均显著降低，表明调节性T细胞在避免胎儿免疫排斥中发挥着重要的作用。同时NK细胞作为早期妊娠蜕膜中的优势淋巴细胞亦对妊娠的维持起着重要的作用，不明原因反复自然流产患者蜕膜NK细胞数量和活性比正常妊娠妇女明显升高，同时CD56^＋CD16^＋／CD56^＋CD16^-NK细胞比例失衡。由此可见，妊娠早期不明原因反复自然流产的发生与蜕膜中淋巴细胞的异常表达相关，通过对这种复杂机制的研究可以为不明原因反复自然流产的预防和治疗提供依据。     

Leukocyte activation in the decidua of chromosomally normal and abnormal fetuses from women with recurrent abortion

As part of our continuing programme to investigate immunological causes of unexplained recurrent pregnancy losses, we studied subpopulations of white blood cells and their activation status in decidua of women with a history of recurrent spontaneous abortion (RSA). We differentiated specifically between normal karyotyped male fetuses and abnormal karyotyped fetuses with trisomy 16 because trisomy 16 is not compatible with life and is thus a non-controversial cause of spontaneous miscarriage. Leukocytes were counted in paraffin-embedded decidua after immunohistological staining for CD45 (LCA), CD3, CD56, CD68, CD69 and CD25. Numbers of activated versus non-activated T lymphocytes, NK cells and macrophages were compared in decidua from women with: (i) unexplained RSA who had a normal male karyotype (n = 17) miscarriage; (ii) unexplained RSA who had a trisomy 16 (n = 21) miscarriage; and (iii) normal gestationally age-matched first trimester pregnancies following elective termination procedures (n = 20). Significantly more activated leukocytes were detected in the decidua of women with unexplained RSA who had a normal male karyotype compared to the other groups (P < 0.0001). In addition, numbers of cells comprising the major leukocyte subpopulation, CD56+ NK cells, appeared reduced in the decidua of women with unexplained RSA compared to decidua from women having elective terminations. Increased numbers of activated leukocytes in the decidua of women with a history of unexplained recurrent pregnancy loss who had a normal karyotyped pregnancy provide evidence that cellular immunity may be involved in unexplained recurrent pregnancy loss.     

Decidual T lymphocyte activation in hydatidiform mole

AIM: To quantify and compare decidual leucocyte subpopulations in complete and partial hydatidiform molar pregnancy with those in normal early pregnancy. METHODS: Decidual leucocytes were characterised using an avidin-biotin technique and a panel of monoclonal antibodies in formalin fixed, paraffin embedded decidual tissues from 10 normal first trimester pregnancy terminations and from 13 partial and 13 complete hydatidiform moles. Immunostained cells were fully quantitated and differences between subject groups were analysed using the Mann-Whitney test. T lymphocyte populations were further characterised using double immunohistochemical labelling. RESULTS: The numbers and percentages of CD3+ and CD4+ T cells were significantly increased in complete hydatidiform moles compared with partial moles and normal early pregnancy decidua. No differences were found in the number or percentage of CD8+ T cells. The CD8+ to CD4+ T cell ratio decreased significantly in complete mole compared with partial mole and normal decidua. The numbers and percentages of CD45RO+ cells increased significantly in both partial and complete hydatidiform mole compared with normal first trimester decidua. Double labelling confirmed that 50% of CD3+ T cells in complete and partial molar pregnancy coexpressed CD45RO, compared with 30% in normal pregnancy. Other leucocyte populations (eGLs, macrophages, B cells, and classical natural killer cells) did not differ between complete and partial mole and normal pregnancy decidua. CONCLUSIONS: The presence of an increased population of activated decidual CD45RO+ T cells in complete and partial molar pregnancy suggests altered maternal immune responses against molar trophoblast.     

Immunoregulatory activity of decidua in spontaneous early pregnancy loss.

The present study aimed to address whether the immunoregulatory properties of the molecules secreted within decidua were altered in women suffering spontaneous miscarriage, compared with apparently normal fertile women. Unfractionated decidual cells from 22 women undergoing therapeutic pregnancy terminations and 25 women experiencing a sporadic spontaneous early pregnancy loss were isolated, cultured for 24 h and 72 h, and supernatants were collected. The effect of decidual supernatants on phytohaemagglutinin (PHA)-induced peripheral blood lymphocyte proliferation was investigated. Immunosuppressive activity was detected in 24 h cell culture supernatants from 91% of therapeutic abortion cases compared with only 64% of spontaneous abortion samples; 72 h supernatants from all of therapeutic abortion samples and 90% of spontaneous abortion cases suppressed lymphoproliferation. The remaining spontaneous abortion samples (36% of 24 h supernatants; 10% of 72 h supernatants) enhanced or had no effect on lymphocyte proliferation. Enhancement of lymphocyte proliferation was not observed in therapeutic abortion samples, and the association between stimulation of cell proliferation and spontaneous abortion was significant for 24 h decidual cell supernatants at 50% concentration (P = 0.02). These findings suggest that in a subgroup of women experiencing spontaneous early pregnancy loss, soluble factors within decidua display altered immune responses that may be implicated in the complex process of fetal rejection.     

Apolipoprotein E4 Allele and Recurrent Pregnancy Loss: Larger Samples Are Still Needed

Citation Nakashima A, Ito M, Shima T, Bac ND, Hidaka T, Saito S. Accumulation of IL‐17‐positive cells in decidua of inevitable abortion cases. Am J Reprod Immunol 2010 Problem Th17 cells, a new subset of helper T cells, have been focused on as a producer pro‐inflammatory cytokines. It is, however, still unknown how Th17 cells affect pregnancy outcome. We investigated the expression of IL‐17‐producing cells in human spontaneous abortion. Method of study IL‐17 expression was analyzed in decidual tissues among normal pregnancy, missed abortion, and inevitable abortion cases by immunohistochemistry and flow cytometry. Results IL‐17⁺ cells were accumulated in decidua and were detected in decidual CD4⁺ T cells and few decidual CD8⁺ T cells in spontaneous abortion cases. The number of decidual IL‐17⁺ cells in inevitable abortion cases involving active genital bleeding was significantly higher than that in normal pregnancy cases (P < 0.05). On the other hand, there were no significant differences in the numbers of decidual IL‐17⁺ cells between missed abortion cases and normal pregnancy subjects. Furthermore, the number of IL‐17⁺ cells was positively correlated with the number of neutrophils in spontaneous abortion cases. Conclusion IL‐17⁺ cells might be involved in the induction of inflammation in the late stage of abortion, but not in the early stage of abortion.     

Proportion of CD56+3+ T cells in decidual and peripheral lymphocytes of normal pregnancy and spontaneous abortion with and without history of recurrent abortion

PROBLEM: The present study investigated the proportion of CD56+3+ T cells in maternal peripheral and decidual lymphocytes in normal pregnancy and spontaneous abortion with and without history of recurrent spontaneous abortion (RSA). METHOD OF STUDY: Maternal peripheral blood and decidua were taken from normal pregnancies and missed abortions with and without RSA. Decidual lymphocytes were prepared from decidual tissue and analyzed by flow cytometry. RESULTS: In normal pregnancy, the percentages of CD56+3+ T cells in decidual lymphocytes did not differ from those in the peripheral blood. However, the proportion of CD56+3+ T cells in decidual CD3+ T cells increased higher than that in the peripheral CD3+ T cells. The percentages of decidual CD56+3+ T cells in missed abortions with and without RSA were lower than those in normal pregnancies. CONCLUSION: CD56+3+ T cells may play a role in the maintenance of pregnancy. The phenomenon, where the proportion of CD56+3+ T cells in decidual lymphocytes decreases, may be due to an immunologic event leading to missed abortion.     

Decrease of T-helper 2 and T-cytotoxic 2 cells at implantation sites occurs in unexplained recurrent spontaneous abortion with normal chromosomal content

BACKGROUND: In normal pregnancy, predominant type 2 cytokines help maintain pregnancy, and a T-helper (Th)1 type response is associated with unexplained recurrent spontaneous abortion (RSA). However, Th2 and T-cytotoxic (Tc)2 cells have not been localized at the implantation site in RSA. METHODS: Twenty-one cases with RSA were classified into RSA with normal chromosomal content (RSA-N, n = 10) and RSA with abnormal chromosomal content (RSA-A, n = 11). As a control, we selected 15 gestational age-matched cases of induced abortion with no history of spontaneous abortion. We immunostained paraffin-embedded decidual sections for a specific Th2 and Tc2 cell marker termed 'chemo-attractant receptor-homologous molecule expressed on Th2 cells (CRTH2)' and T-cell markers CD3 and CD8. The numbers and percentages of Th2 (CRTH2(+)CD8(-)CD3(+)) and Tc2 (CRTH2(+)CD8(+)) cells were compared between the decidua basalis and decidua parietalis. RESULTS: Th2 and Tc2 cells accumulated in the decidua basalis in normal pregnancy. Accumulation of Tc2 cells and both Th2 and Tc2 cells decreased in the decidua basalis in RSA-A and RSA-N respectively. The number and percentage of Th2, and Tc2 cells in the decidua parietalis were similar in normal pregnancy, RSA-A and RSA-N. CONCLUSION: Decreased Th2 and Tc2 cells at the implantation site may contribute to RSA-N.     

Deficiency of decidual IL-10 in first trimester missed abortion: a lack of correlation with the decidual immune cell profile

PROBLEM: To determine if first trimester missed abortion decidua is characterized by an altered immune cell profile and/or a modified interleukin (IL)-10 and interferon (IFN)-gamma production pattern compared with decidua from elective termination. METHOD OF STUDY: Flow cytometry and immunohistochemistry techniques were used to determine the decidual immune cell phenotypic profile and production pattern of IL-10 and IFN-gamma in cases of elective termination (n = 14) and missed abortion (n = 12). RESULTS: Both groups had a similar proportion of CD56+ CD16-, CD56+ CD16+, CD19+, CD3+, CD4+, CD8+, alphabeta T cells and gammadelta T cells. The majority of alphabeta and gammadelta positive T cells in both groups coexpressed the natural killer (NK) cell marker CD56, but lacked cell surface expression of CD3. Diminished decidual IL-10 staining was noted in 7/10 missed abortion cases compared with none of the elective termination cases (n = 12) (P = 0.007). A uniform decidual IFN-gamma staining pattern was observed in both groups. CONCLUSION: Decreased IL-10 production coupled with a sustained IFN-gamma presence noted in missed abortion compared with elective termination cases suggest that these cytokines may be important determinants in pregnancy outcome. In contrast, differences in the proportion of immune cells between both groups may not be a critical factor in early pregnancy loss. In normal pregnancy, decidual alphabeta and gammadelta positive T cells with reduced CD3 on their cell surface may be intrinsically restricted in T-cell receptor (TCR)-mediated activation.     

Flow-cytometric analysis of immune cell populations in human decidua from various types of first-trimester pregnancy.

We undertook an investigation in which flow cytometry was used to characterize immune cell populations in the decidua of first-trimester normal pregnancies, spontaneous abortions, and ectopic pregnancies in comparison to the nonpregnant endometrium to demonstrate how the proportions of immunocompetent cell populations at the fetomaternal interface are influenced by the presence and state of a fetoplacental allograft. No significant differences were found in the decidua of the different types of first-trimester pregnancy in the proportions of the CD45+, CD14+, CD3+, CD4+, CD8+, CD19+, CD3-/CD16+ and/or CD56+, CD3+/CD16+ and/or CD56+, CD4+/Leu-8+, CD4+/Leu-8-, CD8+/CD11b+, CD8+/CD11b-, and CD3+/HLA-DR- decidual leukocyte subsets. However, the percentage of decidual CD3+/HLA-DR+ cells, which are characteristic of activated T cells, was significantly higher in spontaneous abortions than in normal pregnancies (p less than 0.05). This suggests that the accumulation of decidual leukocytes may be regulated mainly by hormones and/or cytokines rather than by the presence and state of an intrauterine conceptus and that on/off-switching of activation of decidual T cells may be associated with successful maintenance of the implanted embryo.     

Activation status of T and NK cells in the endometrium throughout menstrual cycle and normal and abnormal early pregnancy

Endometrial lymphocytes were studied at all stages throughout the menstrual cycle and early pregnancy by flow cytometry to examine different lymphocyte subpopulations and the expression of the T- and NK-cell activation markers. After pregnancy, CD8⁺CD3⁺ lymphocytes were decreased in the decidua. In both endometrium and decidua, more T cells expressed CD69, CD71, HLA-DR, and CD38 antigens than in peripheral blood. After pregnancy, CD71⁺CD3⁺ lymphocytes were further increased. CD25⁺CD3⁺ lymphocytes decreased significantly in the endometrium and decidua of ectopic pregnancies, but not in the decidua of normal pregnancies. These findings indicate that T cells are regionally activated in the first trimester, and it may be the result of the stimulation by fetal antigens. NK cells were the most abundant cell type in the decidua, which expressed the phenotype CD16⁻ CD56⁺, and CD57⁻CD56⁺. The proportion of activated decidual NK cells was increased in anembryonic pregnancies more than in normal pregnancies, although the total NK subpopulation was similar in both groups. This might result in increased NK cytotoxicity in anembryonic pregnancies. In conclusion, T cells are activated, but NK cytotoxicity is decreased in the decidua of early normal pregnancies. This might be important in the control of trophoblast growth and placental development.     

T and B lymphocyte subsets in patients with unexplained recurrent spontaneous abortion: IVIG versus placebo treatment

PROBLEM: To investigate circulating lymphocyte subsets in women with recurrent spontaneous abortion (RSA) in relation to pregnancy outcome and to treatment with intravenous immunoglobulin (IVIG). METHOD OF STUDY: Forty-one women with a history of unexplained RSA were examined during first trimester of pregnancy before IVIG or placebo treatment and after pregnancy. The results were compared with five healthy, non-pregnant women and five women in the first trimester of normal pregnancy. Circulating lymphocyte subsets with focus on T-cell subpopulations were determined by flow cytometry. RESULTS: The proportions of human leukocyte antigen (HLA)-DR positive T cells (CD3+ HLA-DR+), T-killer/effector cells (CD8+ S6F1+) and B cells (CD19+) were increased, whereas the proportion of T-suppressor/inducer cells (CD4+ CD45RA+) was decreased during first trimester pregnancy of RSA women compared with pregnant normal controls. T and B lymphocyte subsets did not correlate with pregnancy outcome on either IVIG or placebo group. CONCLUSIONS: In RSA patients, the immune system seems to be activated in contrast to the suppression noted in normal pregnancy.     

自然流产模型小鼠蜕膜细胞凋亡及相关基因的表达

目的 通过比较正常妊娠模型小鼠及自然流产模型小鼠蜕膜细胞凋亡及Bcl-2、Bax、Fas、FasL蛋白的表达,从细胞及分子水平探讨自然流产的发病机制.方法建立正常妊娠模型CBAXBALB/c和自然流产模型CBAXDBA/2.用免疫组化SABC法测定两组模型孕13 d蜕膜细胞Bcl-2、Bax、Fas、FasL蛋白的表达,并通过MIAS-2000医用彩色病理图像免疫组化测量系统对其表达进行半定量分析,其结果用平均灰度值表示;同时应用DNA缺口原位末端标记技术(TUNEL)测定两组模型孕13天蜕膜细胞凋亡情况.结果与正常妊娠模型相比,自然流产模型蜕膜细胞Bcl-2蛋白的表达降低(P＜0.01);Bax蛋白的表达明显升高(P＜0.01);FasL的表达明显升高(P＜0.01);Fas的表达两组比较无明显差异(P＞0.05).蜕膜细胞凋亡指数(AI),自然流产模型明显高于正常妊娠模型(P＜0.01).结论 早孕期蜕膜组织细胞凋亡异常是自然流产的机制之一,Bcl-2/Bax,Fas/FasL途径可能是诱导早孕期蜕膜细胞凋亡的重要因素.     

母胎界面树突状细胞CCL17和CCL22表达在母胎免疫耐受中的作用

目的: 检测非孕期子宫内膜和正常妊娠早期及复发性自然流产患者蜕膜中树突状细胞(DC)CCL17和CCL22的表达差异,探讨母胎界面DC在CD4⁺CD25⁺调节性T细胞(Treg)的募集及母胎免疫耐受微环境形成中的作用。方法: 正常早孕组人工流产时、复发性流产组清宫时取其蜕膜,正常未孕组行子宫切除时取其内膜组织。分离蜕膜或子宫内膜单个核细胞,体外诱导培养DC,用real-time PCR法分析3组DC CCL17和CCL22 mRNA的表达水平,ELISA法检测3组DC培养上清液中CCL17和CCL22蛋白的表达。结果: 正常早孕组蜕膜DC CCL17和CCL22 mRNA的表达分别为3.04±0.40和1.83±0.24,均高于正常未孕组(0.85±0.24和0.31±0.08,P<0.01)和复发性流产组(1.65±0.14和0.96±0.09,P<0.01)。正常早孕组蜕膜DC能够持续旺盛分泌趋化因子CCL17和CCL22,在培养的12~96 h内CCL17和CCL22的分泌量逐渐增多。同一时点早孕组DC分泌的CCL17和CCL22均明显高于未孕组和复发性流产组DC分泌的CCL17和CCL22(P<0.01)。结论: 正常妊娠后蜕膜DC表达CCL17和CCL22增强,DC可能通过高表达CCL17和CCL22而增强对CD4⁺CD25⁺Treg的趋化作用,从而在母胎界面的免疫耐受中发挥重要作用,蜕膜DC表达CCL17和CCL22下降可能与复发性自然流产的发病有关。     

Decreased superoxide dismutase expression and increased concentrations of lipid peroxide and prostaglandin F(2alpha) in the decidua of failed pregnancy

To study the possible role of the superoxide radical and its scavenging system in the decidua of early pregnancy, superoxide dismutase (SOD) values and concentrations of lipid peroxide and prostaglandin F(2alpha) (PGF(2alpha)) were analysed in the decidua obtained from normal pregnancy and failed pregnancy. Failed pregnancy was divided into two groups; spontaneous abortion with or without vaginal bleeding. In the spontaneous abortion with vaginal bleeding, total SOD activities, Cu,Zn-SOD activities and Cu,Zn-SOD mRNA values in the decidua were significantly lower, and concentrations of lipid peroxide and PGF(2alpha) were significantly higher, than those in the normal pregnancy and the spontaneous abortion without vaginal bleeding. In contrast, activities and mRNA values of Mn-SOD were significantly higher in the spontaneous abortion with vaginal bleeding than the other two groups. There was no significant difference in all of these parameters between the normal pregnancy and the spontaneous abortion without vaginal bleeding. In conclusion, the decrease in Cu,Zn-SOD expression and the increase in lipid peroxide in the decidua could be involved in the termination of spontaneous abortion, mediated through the increase in PGF(2alpha) synthesis. In other words, Cu,Zn-SOD may contribute to the maintenance of pregnancy by preventing the accumulation of superoxide radicals that cause PGF(2alpha) synthesis.     

Perforin-Expressing Lymphocytes in Peripheral Blood and Decidua of Human First-Trimester Pathological Pregnancies

PROBLEM: We have shown previously that the decidua of first-trimester human pregnancy is heavily infiltrated with perforin-positive cells. The aim was to detect expression of perforin in both decidual lymphocytes (DL) and peripheral blood lymphocytes (PBL) in the first trimester of pathological pregnancies: Anembryonic pregnancy and missed abortion. METHOD: Decidual tissue from a normal pregnancy group and from pathological pregnancies was obtained by vaginal curettage. Perforin (an intracellular antigen) and the cell surface antigens CD3, CD4, CD8, CD16, CD56, CD11c, and CD45RA were quantified simultaneously by flow cytometric analysis. RESULTS: In the missed abortion group, we found: 1) a relative decrease in the frequency of both CD4⁺P⁺ cells and CD56⁺P⁺ cells as well as the mean fluorescence intensity for perforin; 2) a relative increase of CD16⁺P⁺ PBL cells; and 3) a relative increase of CD4⁺ cells in PBL compared with anembryonic pregnancy and normal pregnancy. There was also a significant relative decrease in the proportion of CD4⁺ and CD8⁺ cells among perforin-positive PBL in both anembryonic pregnancy and missed abortion. CONCLUSION: Our results show that significant decreases in the prevalence of perforin-positive lymphoid cells, their subpopulations, and mean fluorescence intensity for perforin are associated with pregnancy failure.     

Increased blood vessel density in decidua parietalis is associated with spontaneous human first trimester abortion.

Spontaneous pregnancy loss affects 15-18% of couples, and a number of potential causes are being discussed. The purpose of the present study was to assess if angiogenic disorders in the decidua of early human pregnancy could be related to spontaneous abortions. First trimester human decidua from elective terminations of normally progressing pregnancies and from missed abortions were investigated immunohistochemically. We quantified vessel density in decidua from normal pregnancies and from abortions by von Willebrand factor (vWF), platelet endothelial cell adhesion molecule (PECAM-1) and CD34 staining. Decidual blood vessel expression of alphavbeta3 integrin was also investigated. Significant increase (P < 0.02) in vessel density was observed in decidua parietalis of abortions, compared to decidua basalis. This increase was detected on slides stained for vWF and CD34, but not for PECAM-1. We observed a 15% increase analysing with vWF and a 77% increase with CD34 staining. alphavbeta3 integrin expression was not significantly different, neither in decidua parietalis from abortion, nor parietalis from normal pregnancies. Our data suggest that the increased vascularization in decidua parietalis from abortions could reflect complex disorders, such as specific cytokine expressions and hypoxia phenomena during the development of the decidua.     

反复自然流产患者母胎界面SOCS3蛋白、TNF-α及IL-10的表达

目的:研究反复自然流产患者蜕膜组织中细胞因子信号转导抑制因子SOCS3,细胞因子TNF-α及IL-10的表达,并与正常妊娠作对照。方法:Western blot检测SOCS3的表达,免疫组织化学法检测细胞因子TNF-α及IL-10的表达。结果:反复自然流产组蜕膜组织中SOCS3的表达明显降低(P<0.01),差异有统计学意义,IL-10表达降低(P<0.01),TNF-α表达增高(P<0.05),差异有统计学意义。结论:与正常妊娠相比,反复自然流产组蜕膜组织中SOCS3蛋白及IL-10表达降低,TNF-α表达增高,差异有统计学意义,说明反复自然流产患者母胎界面Th1/Th2失衡,SOCS3蛋白可能通过与细胞因子的相互调控作用影响Th1/Th2平衡导致流产发生。