输卵管妊娠人输卵管黏膜上皮VDR的表达

目的:探讨输卵管妊娠病理状态下人输卵管黏膜上皮VDR蛋白在受精卵种植部位与非种植部位的表达及其变化。方法:应用免疫组织化学方法检测14例人输卵管妊娠手术切除标本的黏膜上皮细胞VDR蛋白的表达。结果:输卵管妊娠种植部位和非种植部位输卵管黏膜上皮均可检测到VDR蛋白表达,VDR蛋白阳性于输卵管黏膜上皮细胞的细胞核内表达,部分间质平滑肌细胞核内亦可见阳性染色。种植部位输卵管黏膜上皮细胞VDR蛋白表达(5.95±1.81)明显少于非种植部位(7.55±3.20)(P=0.017,P<0.05),有些部位VDR蛋白表达甚至缺如。结论:人输卵管黏膜上皮VDR蛋白表达的改变可能是输卵管妊娠的发病原因之一。     

HOXA9、HOXA11、LIF在输卵管中的表达及与输卵管妊娠的关系

目的:探讨同源框基因HOXA9、HOXA11以及白血病抑制因子(1eukemia inhibitory factor,LIF)在输卵管异位着床中的作用。方法:用免疫组织化学染色方法分别检测36例异位妊娠输卵管和34例正常输卵管HOXA9、HOXA11和LIF蛋白的表达。结果:①HOXA9、HOXA11强阳性(+++)表达率在异位妊娠输卵管中最高,且输卵管着床部位和非着床部位表达率无明显差异;增生期输卵管HOXA9、HOXA11强阳性表达率明显较低,在分泌期输卵管中表达率为0。②LIF强阳性表达仅见于妊娠输卵管,着床部位的表达率高于非着床部位;增生期和分泌期输卵管呈中低水平表达。结论:HOXA9、HOXA11及LIF蛋白表达增加与输卵管妊娠相关。     

雌/孕激素受体和HOXA-9基因在输卵管和异位妊娠输卵管中的表达

目的:探讨雌激素受体(ER)、孕激素受体(PR)和HOXA-9基因在人输卵管中的表达及与输卵管妊娠的关系。方法:采用免疫组化和原位杂交方法对34例正常输卵管和38例妊娠输卵管黏膜中ER、PR和HOXA-9基因表达进行研究。结果:ER、PR在正常增生期和分泌期输卵管黏膜上皮中的表达率较高;在妊娠输卵管黏膜上皮中的表达率明显下降(P<0.01)。HOXA-9基因在正常增生期输卵管中的表达率较高,分泌期输卵管中表达降低,而在妊娠输卵管中表达率又有所增高(高于分泌期输卵管的表达率,P<0.05)。结论:ER、PR在输卵管黏膜上皮中的表达下降和HOXA-9基因表达增强与输卵管妊娠密切相关;在正常分泌期输卵管黏膜上皮中,ER、PR表达水平上调和HOXA-9基因表达下调可能起着屏障作用,防止输卵管着床的发生。     

上皮性钙黏蛋白在人输卵管妊娠种植与非种植部位组织中表达的比较

目的:比较上皮性钙黏蛋白(E-cadherin,E-cad)在人输卵管妊娠种植与非种植部位组织中的表达水平。方法:14例未破裂型输卵管壶腹部妊娠组织标本,均包括种植和非种植部位的组织,分为种植部位组(n=14)和非种植部位组(n=14);并以12例因其它疾患行全子宫加附件切除术的人分泌期正常输卵管壶腹部组织新鲜标本为对照组。采用免疫组织化学法观察E-cad蛋白在输卵管妊娠组织和输卵管黏膜上皮的表达情况,应用荧光定量聚合酶链反应(qRT-PCR)和免疫印迹法(Western blotting)检测其E-cadmRNA和蛋白表达水平。结果:E-cad蛋白表达于人输卵管黏膜上皮纤毛细胞和分泌细胞的胞膜,在细胞之间的连接面表达较强,管腔面表达较弱,纤毛未见表达。在输卵管妊娠组织,E-cad表达于蜕膜细胞、绒毛细胞滋养层细胞和绒毛外滋养细胞的胞膜,绒毛外滋养细胞的阳性显色弱于绒毛细胞滋养层细胞。E-cadmRNA和蛋白在种植部位组的表达显著低于非种植部位组和对照组(P<0.05),非种植部位组与对照组之间表达无显著性差异(P>0.05)。结论:E-cad在输卵管妊娠种植部位表达水平降低,可能与输卵管妊娠发生有密切的联系。     

巨噬细胞移动抑制因子在输卵管妊娠植入部位的表达及其临床意义

目的:通过检测巨噬细胞移动抑制因子(MIF)在输卵管妊娠的植入、非植入部位及正常分泌中期壶腹部输卵管组织中的表达,分析其在输卵管妊娠发生发展中的作用。方法:收集输卵管妊娠患侧输卵管标本30例,分别从植入及非植入部位取材,选择分泌中期正常壶腹部输卵管标本20例,采用链霉菌抗生物素蛋白-过氧化物酶连结(即SP法)免疫组织化学方法结合病理图象半定量分析检测各组标本中MIF的表达。结果:输卵管妊娠植入部位输卵管黏膜组织中MIF表达显著高于非植入部位及正常分泌中期组,差异有统计学意义(P<0.0125);非植入部位组与正常分泌期组MIF表达差异无统计学意义(P>0.0125)。结论:MIF在输卵管妊娠种植部位黏膜上皮中的表达增强,提示MIF可能在输卵管妊娠的发生发展中起重要作用。     

对作为异位妊娠标记物的白血病抑制因子的评价

白血病抑制因子(LIF)是白细胞介素6家族中的一种细胞因子。现认为EIF在妊娠种植过程中起重要作用。设想LIF作为异位妊娠绒毛种植和对输卵管损伤的一种早期标记物,为测定血清LIF对诊断异位妊娠的价值,对Cincinnati大学医学院收集的40例血清β-hCG阳性者抽血作ELISA法血     

HOXA-10、PR在输卵管粘膜的表达与输卵管妊娠发生的关系

目的:探讨HOXA-10、PR在输卵管妊娠发生中的作用。方法:用免疫组化法分别检测20例输卵管妊娠患者异位着床部位粘膜组织,20例正常分泌期输卵管粘膜组织及20例正常宫内早孕期子宫蜕膜组织中HOXA-10基因、PR的蛋白表达水平。结果:(1)HOXA-10基因在输卵管妊娠患者异位着床部位的阳性表达明显高于正常分泌期输卵管粘膜的表达,两组差异有统计学意义(P<0.05);但接近正常早孕期子宫蜕膜组织中的表达,两组差异无统计学意义(P>0.05);(2)PR在输卵管妊娠患者异位着床部位上皮细胞中的阳性表达明显低于在正常分泌期输卵管的表达,两组比较差异具有统计学意义(P<0.05);但接近于在正常早孕期子宫蜕膜的表达,两组比较差异无统计学意义(P>0.05);(3)PR在输卵管妊娠患者异位着床部位间质中的阳性表达明显高于正常分泌期输卵管的表达,两组差异有统计学意义(P<0.05);但接近正常早孕期子宫蜕膜的表达,两组差异无统计学意义(P>0.05)。结论:输卵管妊娠异位着床部位HOXA-10基因表达增强,上皮细胞PR表达下降或缺失和间质细胞表达增强,与输卵管妊娠发生密切相关。     

沙眼衣原体感染与输卵管妊娠的关系

沙眼衣原体感染与输卵管妊娠的关系邹先进蔡兰蔡明秀异位妊娠是严重危害妇女身体健康的疾病之一。近几十年来，在世界范围内，其发病率有明显增高的趋势［１］。有学者观察到，异位妊娠患者其血清内沙眼衣原体抗体增高，但未能从异位妊娠的输卵管内培养分离出沙眼衣原体（...     

白血病抑制因子在早期妊娠、先兆流产及难免流产患者蜕膜组织中表达的研究

目的探讨白血病抑制因子(LIF)在蜕膜组织中的表达,及其与早期妊娠、流产的关系. 方法采用放射免疫方法检测正常早孕妇女(正常早孕组)、先兆流产妇女(先兆流产组)及难免流产妇女(难免流产组)的血清孕酮及人绒毛膜促性腺激素(hCG)水平,并采用逆转录-聚合酶链反应(RT-PCR)技术对3组孕妇蜕膜组织中LIF-mRNA的表达进行定量分析.结果 (1)孕酮及hCG水平在3组孕妇间的比较正常早孕组孕妇血清中孕酮、hCG水平分别为(91.5±27.2) nmol/L、(69.9±14.9) kU/L,先兆流产组孕妇分别为(88.4±24.7) nmol/L、(57.6±11.2) kU/L,两组孕妇血清孕酮、hCG水平比较,差异均无显著性(P>0.05);而难免流产组孕妇血清孕酮、hCG水平分别为(33.1±19.6) nmol/L、(10.3±3.2) kU/L,与前两组分别两两比较,差异均有极显著性(P<0.01).(2)LIF-mRNA平均相对含量在3组孕妇间的比较正常早孕组孕妇为2.10±0.32;先兆流产组孕妇为1.92±0.20;难免流产组孕妇为0.70±0.06.正常早孕组与先兆流产组比较,差异无显著性(P>0.05).而难免流产组与前两组分别行两两比较,差异均有显著性(P<0.05).结论 LIF-mRNA在早期妊娠蜕膜组织中的表达量降低,可能是导致hCG及孕酮分泌下降,最终造成难免流产的原因之一.     

输卵管妊娠与病毒感染关系的回顾性研究

输卵管妊娠的病因研究越来越受到重视[1 ] ,感染仍被认为是高危因素之一 ,但对引起感染的病原体仍不明确。关于沙眼衣原体、解脲支原体与输卵管妊娠关系的研究 ,已有较多报道 ,有关病毒与输卵管妊娠的关系研究较少。我们对输卵管妊娠石蜡包埋组织中人巨细胞病毒 (ＨＣＭＶ)、单纯疱疹病毒Ⅱ型 (ＨＳＶ Ⅱ )及人类细小病毒Ｂ19进行检测 ,回顾性探讨输卵管妊娠与ＨＣＭＶ、ＨＳＶ Ⅱ及人类细小病毒Ｂ19感染的关系。一、资料与方法1 研究对象 :38份标本来自 1998年 3月至 2 0 0 1年 2月期间 ,解放军第二五一医院和内蒙古自治区宝昌人民医院收治…     

人无血清输卵管上皮细胞模型与小鼠胚胎共培养的研究

目的了解２细胞期小鼠胚胎与人输卵管上皮细胞体外无血清共培养中的发育状况。方法配制无血清培养液,予小鼠超排卵并取２细胞期胚胎,将９０个２细胞期小鼠胚胎与人输卵管上皮细胞在无血清培养液中进行体外共培养,另以９０个同期胚胎在无辅助细胞的培养液中培养作对照,每日在显微镜下观察小鼠胚胎发育情况。结果共培养的胚胎有８２％发育到桑椹胚,７７％形成囊胚,６３％胚胎孵化。对照者仅４５％发育到桑椹胚,１３％到初级囊胚,无孵化胚胎。共培养胚胎发育速度快,碎片率明显低于对照者。结论人输卵管上皮细胞与小鼠胚胎共培养可以促进胚胎体外发育,并提高胚胎发育质量。     

Previous tubal ectopic pregnancy raises the incidence of repeated ectopic pregnancies in In Vitro fertilization-embryo transfer patients

Purpose  To investigate the incidence of Tubal Ectopic Pregnancies (TEP) in IVF-ET patients with respect to the status of the fallopian tubes after a previous TEP. Material and methods  This retrospective study compares patients undergoing 481 IVF-ET cycles after conservatively or surgically treated TEP(s) with a Control Group (idiopathic or male factor for IVF-ET indication). Medical reports of surgery and/or hysterosalpingograms prior to the IVF cycles classified the status of the fallopian tubes. Results  12 TEPs (8.95%/Pregnancies (PR)) occurred in the Study Group. In the Control Group one TEP (0.75%/PR; p < 0.001) was found. Smoking increased the probability of TEPs (p = 0.0028) and of pathological pregnancies (abortion, biochemical and ectopic PR; (p = 0.0411)). For statistic evolution logistic regression (PROC GENMOD) and a repeated measure model were applied. Conclusion  Women with a previous TEP should be informed about the significantly increased risk for a further TEP in IVF-ET treatment, especially if they are smoking. Capsule Tubes after a Tubal ectopic pregnancy (TEP) and smoking lead to a significant higher number of repeated TEPs in following IVF-ET programs.     

Modulation of leukemia inhibitory factor gene expression and protein biosynthesis in the human fallopian tube

OBJECTIVE: The fallopian tube is the site of fertilization and early embryonic growth and a common site of ectopic implantation. Although the factors responsible for early embryogenesis and implantation are incompletely understood, leukemia inhibitory factor may have an important role in early embryonic development and implantation. We set out to evaluate the production and modulation of leukemia inhibitory factor in the fallopian tube. STUDY DESIGN: We first investigated leukemia inhibitory factor messenger ribonucleic acid levels in fallopian tubes. We then investigated leukemia inhibitory factor messenger ribonucleic acid and protein production in tubal epithelial and stromal cell cultures. RESULTS: Leukemia inhibitory factor messenger ribonucleic acid is expressed in the fallopian tube with only slight variation during the menstrual cycle; however, it is markedly elevated in association with ectopic pregnancy. The level is higher in the tubal mucosa than in the remaining layers and is higher in the more distal segments of the fallopian tube. Estradiol and progesterone did not modulate leukemia inhibitory factor expression in epithelial or stromal cell cultures. Interleukin-1α, tumor necrosis factor-α, and transforming growth factor-β enhanced leukemia inhibitory factor expression in epithelial and stromal cells, with transforming growth factor-β1 enhancing expression by fourfold in stromal cells. Epithelial cells secreted high levels of leukemia inhibitory factor compared with stromal cells (332 ± 89 vs 25 ± 42 pg/mg total protein). Yet stromal cells treated with transforming growth factor-β alone or in combination with epidermal growth factor and platelet-derived growth factor, as well as TNF-α alone or in combination with interleukin-1α enhanced secretion of leukemia inhibitory factor at or above the levels found with epithelial cells. CONCLUSIONS: We speculate that the high constitutive levels of leukemia inhibitory factor expressed in the ampullary portion of the fallopian tube may play a role in early embryonic development. Additionally, elevated expression with ectopic implantation and the marked induction of secretion in the tubal stroma by growth factors and cytokines suggest a link between inflammation, leukemia inhibitory factor, and tubal ectopic pregnancies. (Am J Obstet Gynecol 1996;175:1611-9.)     

Deoxyribonucleic acid of Chlamydia trachomatis in fresh tissue from the Fallopian tubes of patients with ectopic pregnancy

OBJECTIVES: The role of persistent chlamydial infection of the Fallopian tubes in ectopic pregnancy is still unresolved. Therefore, we examined tissue of the Fallopian tubes from patients with ectopic pregnancy for the presence of Chlamydia trachomatis. In addition, other markers of C. trachomatis infection implicated in the pathogenesis of tubal damage were studied including antibodies to heat shock protein 60 of chlamydial and human origin. STUDY DESIGN: Fresh frozen tubal tissue from 55 patients with ectopic pregnancy in a hospital setting were examined for the presence of C. trachomatis DNA by polymerase chain reaction (PCR) and blood sample were analysed for antibodies to C. trachomatis including heat shock protein 60 (hsp60). RESULTS: Chlamydial DNA was not detected in any of the 55 tubal specimens using a commercial test, Cobas Amplicor, Roche, and an in-house real time PCR able to detect a few copies of the organism. Logistic regression showed that chlamydial IgG antibodies were more common in a subgroup of patients with previous PID than in controls (OR=7.84, CI 1.78-34.6). Specific antibodies to hsp60 of chlamydial (OR=7.00, CI 1.50-32.6) but not of human origin (OR=2.13, CI 0.14-31.6) were associated with ectopic pregnancy in this group. CONCLUSIONS: No evidence of persistent infection of C. trachomatis in the fallopian tubes at the time of ectopic pregnancy was found in this study.     

Developmental potential of isolated blastomeres from early mouse embryos in the presence and absence of LIF and GM-CSF

Purpose The aim of this study was to investigate the developmental potential of isolated blastomeres in the presence and absence of leukemia inhibitory factor (LIF) and granulocyte–macrophage colony stimulating factor (GM-CSF). Methods The blastomeres of two (1/2) and eight cells (1/8) embryos were isolated and cultured in T6 medium in the presence and absence of LIF (1,000 IU/ml) and or GM-CSF (2 ng/ml) up to 120 h. The diameter and cell number of blastocysts were measured. Results The developmental rates of 1/2 isolated blastomeres developed to blastocysts stages in the presence and absence of LIF and GM-CSF were 45.80, 35.10 and 48.66, 41.66, respectively. The diameter of blastocysts was higher in GM-CSF group and total cell number of blastocyst in both treated groups was higher than control (P < 0.05). No 1/8 blastomeres developed to morula and blastocyst stages. Conclusions LIF and GM-CSF could improve the development of 1/2 isolated blastomeres. Capsule GM-CSF improved the developmental potential and the quality of isolated blastomeres derived from mouse two cells embryo.     

Predictive power of serum CA-125 and LDH in the outcome of first trimester pregnancies with human chorionic gonadotropin levels below discriminatory zone

Background  The present study aims to investigate the predictive power of serum CA-125 and lactate dehydrogenase (LDH) for evaluating the outcome of first trimester pregnancies with beta human chorionic gonadotropin levels below discriminatory zone (≤1,000 mIU/mL). Methods  A total of 107 women with tubal ectopic pregnancies (30 ruptured and 77 unruptured), 105 women with normal intrauterine pregnancies and 100 women with intrauterine abortions were eligible for the study. Results  Women with intrauterine abortion were found to have significantly higher CA-125 and LDH levels compared to women with ectopic and normal intrauterine pregnancies. Ruptured tubal pregnancies resulted in significantly higher CA-125 and statistically similar LDH levels compared with unruptured tubal pregnancies. Although CA-125 levels were found to be unrelated to gestational age in normal intrauterine normal and abortive as well as ruptured and unruptured ectopic pregnancies; LDH levels were directly correlated with gestational age in ruptured tubal ectopic pregnancies. Discussıon  Consequently, the ability to determine the disintegration of ectopic trophoblastic or fetal tissues would be of great value in the management of hemodynamically stable patients with beta hCG levels below discriminatory zone. Intrauterine abortive pregnancies seem to yield high serum CA-125 concentrations combined with high LDH levels which indicate more extensive trophoblastic tissue damage than caused by intrauterine and ectopic pregnancies.     

中药红花浸液对植入期子宫内膜白血病抑制因子表达水平的影响

目的:探讨中药红花抗早孕过程中的生物学作用机理。方法:随机将受精后第2天的孕鼠分为3个实验组和对照组,分别经口给予不同浓度的红花液和生理盐水,连续3天,停药后24天取子宫,石蜡包埋切片,进行HE和免疫组化染色,将染色结果输入图像分析仪,观察子宫内膜的形态和白血病抑制因子(leukemia inhibitory factor,LIF)蛋白的表达,并作定量分析。结果:实验组子宫内膜形态有异常改变;免疫组化染色表明,随着药物剂量的增多,子宫内膜细胞LIF蛋白的表达逐渐减少;但对照组呈强阳性表达。结论:中药红花作用于孕鼠子宫内膜细胞,抑制LIF蛋白的表达,从而影响胚胎着床,起到了抗早孕的作用。     

The role of leukemia inhibitory factor in tubal ectopic pregnancy

Introduction

Ectopic pregnancy is unique to humans and a leading cause of maternal morbidity and mortality. The etiology remains unknown however factors regulating embryo implantation likely contribute. Leukemia inhibitory factor (LIF) has roles in extravillous trophoblast adhesion and invasion and is present in ectopic implantation sites. We hypothesised that LIF facilitates blastocyst adhesion/invasion in the Fallopian tube, contributing to ectopic pregnancy.

Methods

We immunolocalised LIF receptor (R) in tubal ectopic pregnancy (N = 5). We used an oviduct cell line (OE-E6/E7) to model Fallopian tube epithelial cells and a trophoblast spheroid co-culture model (HTR-8/SVneo cell line formed spheroids) to model blastocyst attachment to the Fallopian tube. We examined LIF signaling pathways in OE-E6/E7 cells by Western blot. The effect of LIF and LIF inhibition (using a novel LIF inhibitor, PEGLA) on first-trimester placental outgrowth was determined.

Results

LIFR localised to villous and extravillous trophoblast and Fallopian tube epithelium in ectopic pregnancy. LIF activated STAT3 but not the ERK pathway in OE-E6/E7 cells. LIF stimulated HTR-8/SVneo spheroid adhesion to OE-E6/E7 cells which was significantly reduced after PEGLA treatment. LIF promoted placental explants outgrowth, while co-treatment with PEGLA blocked outgrowth.

Discussion

Our data suggests LIF facilitates the development of ectopic pregnancy by stimulating blastocyst adhesion and trophoblast outgrowth from placental explants. Ectopic pregnancy is usually diagnosed after 6 weeks of pregnancy, therefore PEGLA may be useful in targeting trophoblast growth/invasion.

Conclusion

LIF may contribute to the development of ectopic pregnancies and that pharmacologically targeting LIF-mediated trophoblast outgrowth may be useful as a treatment for ectopic pregnancy.