Meis1在子宫内膜异位症不孕患者子宫内膜中的表达研究

目的:初步探索HOXA10的辅因子(Meis1)与子宫内膜异位症(EMs)患者不孕和发病的相关性。方法:采用免疫组织化学方法进行组织学定位并进行半定量分析,采用Westernblot-ting方法在蛋白水平上进行定量分析,检测EMs不孕患者异位和在位子宫内膜中Meis1的表达水平。结果:免疫组织化学结果显示,Meis1在异位内膜和在位内膜中仅有弱表达,而在正常同期内膜中呈较明显的阳性表达,差异显著(P<0.01);比较Meis1在分泌中期在位内膜与正常内膜中的表达,差异亦有显著性(P<0.01)。Westernblotting显示,Meis1在分泌中期在位内膜中仅有弱表达,而在同期正常内膜中呈高表达(P<0.001)。结论:Meis1在EMs患者分泌中期在位内膜中低表达,可能是影响子宫内膜容受性的建立,从而影响胚胎着床导致不孕的重要因素之一。同时,Meis1在异位内膜中的低表达说明异位内膜可能对体内雌、孕激素正常调控具有抵抗性,异位内膜细胞具备了对抗凋亡的能力,提示Meis1可能参与了EMs的发生与发展。     

单核细胞趋化蛋白-1在子宫内膜异位症患者子宫内膜组织中的表达

目的检测单核细胞趋化蛋白-1（MCP-1）在子宫内膜异位症(内异症)患者子宫内膜组织中的表达情况,并探讨其与内异症发病的关系。方法内异症患者30例作为研究组,非内异症患者20例作为对照组。用半定量逆转录聚合酶链反应（RT-PCR）方法检测两组子宫内膜组织中MCP-1信使核糖核酸(mRNA)的阳性表达率及相对水平。结果研究组26例(87%)内膜组织中可检测到MCP-1mRNA的表达,其中19例为强阳性表达,但其表达强度与内异症的严重程度无明显相关性。对照组15例(75%)内膜组织中可检测到MCP-1mRNA表达,仅3例为强阳性表达。研究组内膜组织中MCP-1mRNA的表达强度高于对照组(两组相对表达强度分别为0.746±0.345及0.460±0.341,P<0.05)。结论内异症患者的子宫内膜组织中MCP-1mRNA的表达增强,MCP-1对内异症的发病有一定促进作用。     

白细胞介素1受体Ⅱ在正常子宫内膜及子宫内膜异位症患者在位和异位内膜组织中的表达

子宫内膜异位症(内异症)可能是一种自身免疫性炎症疾病。内异症患者腹腔液、在位内膜和异位内膜中都可观察到细胞因子的失衡和表达异常。白细胞介素1(interleukin-1，IL-1)可通过多个通路导致内异症的发生。本研究采用RT—PCR技术和免疫印迹法，检测了IL-1受体Ⅱ(IL-1RⅡ)基因及蛋白在正常子宫内膜以及内异症患者在位和异位内膜中的表达，现将结果报道如下。     

Toll样受体与子宫内膜及子宫内膜异位症

子宫内膜异位症(EMs)发病机制尚未完全阐明.大量研究表明,免疫因素在EMs的发病机制中起重要作用.EMs免疫应答异常主要是巨噬细胞数量和活性增加及其分泌产物,如生长因子、细胞因子和血管生成因子的改变.Toll样受体(TLRs)识别特异性的病原体相关分子模式,启动和介导免疫应答,在固有免疫中发挥重要作用,并诱导产生适应性免疫反应.TLRs在正常子宫内膜中的生理作用以及在EMs中的相关研究已逐步开展,对其深人认识和研究将为EMs诊断、治疗和预后判断提供新思路和手段.     

FOXM1在大鼠子宫内膜异位症中的表达

目的:研究FOXM1在子宫内膜异位症大鼠模型中的表达,探讨其在内异症中的作用。方法:以雌性未孕Wistar大鼠自身作为供体,取其子宫内膜,采用自体皮下移植法建立内异症大鼠模型。假手术组作为对照组。术后观察28天,测量异位病灶体积。取建模成功的大鼠异位病灶与正常对照组大鼠的子宫内膜,HE染色确定建模成功。免疫组织化学法和Western blot法检测异位病灶与正常对照组大鼠子宫内膜中FOXM1表达。结果:大体观,异位病灶呈椭圆形囊泡,内含清亮液体,表面有新生血管。组织学证实为异位内膜。免疫组织化学染色显示,异位内膜中FOXM1表达于细胞核和细胞质中,主要表达于子宫腔上皮细胞和间质细胞。对照组中,FOXM1在在位内膜中几乎不表达。内异症大鼠异位病灶和在位内膜中FOXM1表达量分别为1.439±0.267和0.886±0.286,差异有统计学意义(P0.05)。结论:异位病灶中的FOXM1表达明显高于在位内膜,其表达增高可能与异位内膜的恶性增殖有关。     

Toll样受体与子宫内膜及子宫内膜异位症

子宫内膜异位症（EMs）发病机制尚未完全阐明。大量研究表明,免疫因素在EMs的发病机制中起重要作用。EMs免疫应答异常主要是巨噬细胞数量和活性增加及其分泌产物,如生长因子、细胞因子和血管生成因子的改变。Toll样受体（TLRs）识别特异性的病原体相关分子模式,启动和介导免疫应答,在固有免疫中发挥重要作用,并诱导产生适应性免疫反应。TLRs在正常子宫内膜中的生理作用以及在EMs中的相关研究已逐步开展,对其深入认识和研究将为EMs诊断、治疗和预后判断提供新思路和手段。     

Cofilin在子宫内膜异位症在位内膜及异位内膜中的表达及意义

目的:探讨子宫内膜异位症(EMT)在位内膜及异位内膜中候选基因cofilin的表达在EMT发生和发展中的作用.方法:选取我院35例经病理证实为EMT的在位内膜及异位内膜[增殖期17例,分泌期18例;轻度组(Ⅰ、Ⅱ期)18例,重度组(Ⅲ、Ⅳ期)17例]为研究组,以同期16例非EMT患者的子宫内膜标本为正常对照组(增殖期7例,分泌期9例).应用原住杂交方法检测cofilin的表达,并对各组内膜中cofilin表达水平进行统计学分析.结果:研究组的在位内膜cofilin表达水平(2.2569±1.0005)明显高于对照组(1.2525±0.7549)(P<0.01);研究组中EMT异位内膜cofilin表达水平(4.2274±1.2091)明显高于EMT在位内膜(2.2569±1.0005)(P<0.01);研究组中EMT重度组在位内膜及异位内膜cofilin表达水平(分别为2.6941±0.9517及4.5965±1.0353)高于轻度组(分别为1.8439±0.8809及3.8789±1.2846)(P<0.01).对照组内膜组织和研究组中在位内膜及异位内膜的分泌期与增殖期cofilin表达水平比较,差异均无统计学意义(P>0.05).结论:EMT患者在位内膜中cofilin表达水平异常升高在该病的发生、发展中可能起一定作用.     

半乳糖凝集素-1在子宫内膜异位症大鼠模型异位及在位内膜中的表达

目的:研究半乳糖凝集素-1(gal-1)在大鼠子宫内膜异位症(EMs)模型异位及在位组织中的表达。方法:选取12只性成熟雌性未孕Wistar大鼠,取一侧宫角子宫内膜,采用自体移植法建立EMs大鼠模型。术后28天再次开腹,将建模成功的大鼠作为自身对照,取其异位病灶与在位子宫内膜,苏木精-伊红(HE)染色鉴定组织学特征。免疫组织化学(IHC)法、实时荧光定量逆转录聚合酶链反应(qRT-PCR)及蛋白免疫印迹(Western blot)法检测异位病灶与在位内膜中gal-1表达。结果:肉眼观异位病灶呈椭圆形囊泡状,内含清亮或咖啡色液体,表面及周围有新生血管。组织学证实为异位内膜。造模成功率为83.33%。IHC显示,gal-1表达于异位及在位子宫内膜基质;QRT-PCR定量分析表明,异位内膜gal-1 mRNA表达量高于在位内膜(P0.05);Western blot结果示,异位内膜gal-1蛋白水平升高(P0.05)。结论:大鼠EMs异位内膜中gal-1表达高于在位内膜,为该靶点参与EMs的机制及治疗的研究打下基础。     

TWEAK在子宫内膜异位症在位和异位内膜上的表达

目的:探讨肿瘤坏死因子样凋亡的微弱诱导剂(TWEAK)在子宫内膜异位症(EMs)发病的关系。方法:采用实时定量逆转录-聚合酶链反应(Real-time RT-PCR)和免疫组化、Western Blot方法检测EMs患者在位内膜、异位病灶中TWEAK mRNA和蛋白的表达,并与正常对照子宫内膜比较。结果:TWEAK蛋白表达于子宫内膜的腺上皮细胞和间质细胞的胞浆内。与正常对照组内膜和在位组内膜相比,TWEAK mRNA和蛋白在异位内膜上表达量下调(P<0.05),且无论是EMs在位内膜还是对照组内膜,其增生期TWEAK mRNA表达明显低于分泌期(P<0.05)。结论:TWEAK在子宫内膜中表达,表达量在分泌期明显升高。EMs患者异位子宫内膜TWEAK表达降低,可能导致子宫内膜细胞的凋亡水平下降,参与EMs的发生发展过程。     

Trem-1在子宫内膜异位症中的表达

目的:研究髓样细胞触发受体(Trem-1)在子宫内膜异位症(endometriosis,EMs)中的表达和作用。方法:应用实时定量RT-PCR方法检测EMs患者外周血白细胞膜表面的Trem-1mRNA表达;同时收集血清及腹腔液,应用ELISA法检测其中可溶性Trem-1(sTrem-1)水平。并以正常妇女为对照,进行比较。结果:EMs组β-actin/Trem-1Ct值为0.77±0.02,正常对照组为0.70±0.04。在EMs组中,Trem-1mRNA表达明显高于对照组(P<0.05)。EMs组血清中sTrem-1的浓度为22.16±5.37ng/ml,正常对照组为9.78±0.84ng/ml,EMs组腹腔液中sTrem-1水平为33.60±5.14ng/ml,正常对照组为14.60±3.13ng/ml,二组均具有显著差异(P<0.01),且腹腔液中的浓度明显高于血清中的浓度(P<0.05)。结论:Trem-1可能在子宫内膜异位症的发生发展过程中具有重要的作用。     

Activin-A secretion is increased in the eutopic endometrium from women with endometriosis

BACKGROUND: Activin is a well-characterised growth and differentiation factor and an important inflammatory mediator. Activin is secreted by normal endometrial glands and stroma and is expressed by endometrial leucocytes. It is also known that the eutopic endometrium from women with endometriosis is functionally different to that from women without endometriosis. In this study, we hypothesise that the endometrial secretion of activin is altered in women with endometriosis. AIMS: To determine whether the expression of inhibin/activin subunits and the secretion of activin-A is different in eutopic endometrium from women with and without endometriosis. METHODS: Endometrial biopsies were obtained from premenopausal, regularly menstruating women with and without endometriosis. Staining intensity for the different inhibin/activin subunits was compared in endometrial and endometriotic biopsies. Activin-A secretion was studied using endometrial explants and endometrial glandular and stromal monolayer cell cultures. RESULTS: The alpha- and betaA-subunits of inhibin/activin were more abundant in eutopic glandular cells from patients with minimal to mild endometriosis compared to women without endometriosis. In patients with endometriosis, the betaB-subunit was more abundant in eutopic stromal cells and endometrial leucocytes. Comparison of paired endometrial and endometriotic biopsies from the same patient did not reveal significant differences for any of the inhibin/activin subunits or activin receptors. Activin-A secretion by glandular and stromal endometrial cells was sevenfold and threefold higher, respectively, in women with endometriosis compared to women without endometriosis. CONCLUSIONS: The expression of inhibin/activin subunits in eutopic endometrium is altered in women with endometriosis, leading to higher levels of activin-A secretion by both glandular cells and stromal cells.     

Oral contraceptives suppress cell proliferation and enhance apoptosis of eutopic endometrial tissue from patients with endometriosis

Objective: To evaluate the effects of administering combination oral contraceptives (COCs) to patients with endometriosis on the regulation of cell growth in the eutopic endometrium.

Design: Prospective study.

Setting: Research institute and clinical fertility center.

Patient(s): Thirteen women with untreated endometriosis and 13 controls.

Intervention(s): Biopsy specimens of the eutopic endometrium were obtained from all subjects. Apoptosis, cell proliferation, and Bcl-2 and Bax expression were examined at the epithelial and stromal levels in the eutopic endometrium from patients with endometriosis before and after 30 days of daily exposure to COCs and from controls.

Main Outcome Measure(s): Apoptotic cells were detected by using the dUTP nick-end labeling assay; Ki-67, Bcl-2, and Bax expressions were assessed by using immunohistochemical techniques.

Result(s): After exposure to COCs, apoptosis was significantly increased in the eutopic endometrium compared with before COC administration, both at epithelial and stromal levels. Cell proliferation was significantly lowered by COCs.

Conclusion(s): COCs showed a positive effect on patients with endometriosis by down-regulating cell proliferation and enhancing apoptosis in the eutopic endometrium.     

Relationship between apoptosis and the number of macrophages in eutopic endometrium from women with and without endometriosis

OBJECTIVE: To investigate the relationship between apoptotic cells and macrophages in the eutopic endometrium of women with and without endometriosis. DESIGN: Retrospective analysis of archival uterine endometrial biopsy specimens. SETTING: Institute for the Study and Treatment of Endometriosis, and university-based pathology and research laboratories. PATIENT(S): Fifty-one women with endometriosis and 24 healthy control subjects without endometriosis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The number of TUNEL+ (terminal deoxynucleotide transferase [TdT]-mediated deoxyuridine triphospate [dUTP] nick end-labeling-positive) (apoptotic) cells and CD68+ (CD68 positive) (macrophages). RESULT(S): Apoptotic cells and macrophage numbers were positively correlated in the eutopic endometrium of women with and without endometriosis. However, the number of apoptotic cells and the macrophage content in the endometrium of women with endometriosis was significantly reduced compared with that of healthy control subjects without endometriosis. Differences between apoptosis and macrophage numbers between the two populations were observed predominantly during the early proliferative phase of the menstrual cycle. CONCLUSION(S): The reduction in apoptosis described for endometrial cells in women with endometriosis may be related to reduced macrophage trafficking into the eutopic endomtrium during the early-proliferative phase of the menstrual cycle.