糖类物质抗着床效应研究——对着床前小鼠子宫内膜的作用

本文选用5种结构不同的糖类物质研究了对小鼠胚泡的抗着床效应,并通过研究这5种不同糖类对小鼠子宫内白细胞浸润现象的诱发作用和对子宫内膜蛋白质代谢的影响,分析了糖类物质的抗着床作用机理。结果表明,糖元和棉子糖不仅对小鼠胚泡着床有显的抑制作用,而且能够在小鼠子宫内引起白细胞浸润现象,并发现小鼠胚泡着床的被抑制与子宫内膜ConA结合蛋白和ConA非结合蛋白的变化有关,推测此变化可能干扰了胚泡着床的识别。     

利洛司酮抗着床效应及其对子宫内膜前列腺素含量的影响

本文观察抗孕激素利洛司酮 (lilopristone ZK98734)对大鼠着床、子宫内膜 PGs含量及血浆孕酮含量的影响。结果显示 :(1 ) 5 mg/ kg ZK98734可明显抑制胚泡着床 (对照组着床率 72 .5 0± 5 .6 8% ;ZK98734组 43.30± 3.86 % ) ;(2 ) ZK98734可促使子宫内膜内源性PGE2 和 PGF2α含量增加 ,5 mg/ kg、1 6 .5 mg/ kg和 2 5 mg/ kg三种剂量呈正相关剂量效应关系 ;(3) ZK98734明显降低血浆孕酮水平 ,三种剂量呈负相关剂量效应关系。提示 :ZK98734可能通过改变着床前子宫孕酮和前列腺素之间的精细平衡 ,干扰着床前子宫“静态”的生理环境 ,不利于胚泡在子宫内附着和发育 ,从而导致着床率降低     

对胚泡着床障碍小鼠子宫内膜容受性的研究

目的:建立胚泡着床障碍小鼠模型,并研究其子宫内膜容受性。方法:于妊娠d4上午利用米非司酮诱导昆明小鼠胚泡着床障碍,12h后处死小鼠,观察小鼠胚泡着床率及平均着床胚泡数,利用光镜观察小鼠子宫内膜形态结构,采用免疫组化SP法检测子宫雌、孕激素受体(ER、PR)表达,采用RT-PCR检测子宫ER、PR基因表达。结果:与对照组相比,模型组小鼠胚泡着床率及平均着床胚泡数明显降低,子宫内膜发育明显受抑制;子宫内膜腺体、间质ER、PR表达范围和强度均显著降低。结论:米非司酮能成功诱导建立胚泡着床障碍模型,其着床期子宫内膜发育受抑制,子宫内膜容受性降低,胚泡着床失败。     

子宫内膜容受性相关调控因子的时序表达及功能

胚胎着床是复杂的程序化的生理过程。子宫内膜仅在极短时期内允许胚泡植入,此时子宫内膜达到最大胚泡种植容受性。子宫内膜容受性形成过程中受多种细胞因子、蛋白分子调控,这些特定调控因子在子宫内膜发育分化过程中呈现较为显著的时空表达特征,对内膜容受性形成有重要作用。相关细胞因子(白血病抑制因子、白细胞介素)、蛋白分子(胎盘蛋白、半乳糖凝集素-1)及特定转录因子(同源框基因)在子宫内膜容受性形成过程中伴随短暂、瞬间性高表达,其表达量为增生期的4～5倍,该时期与着床窗期时间一致,呈现出时空特异性。表明这几类生物活性分子可能与子宫内膜容受性形成密切相关。     

子宫内膜容受性相关调控因子的时序表达及功能

胚胎着床是复杂的程序化的生理过程.子宫内膜仅在极短时期内允许胚泡植入,此时子宫内膜达到最大胚泡种植容受性.子宫内膜容受性形成过程中受多种细胞因子、蛋白分子调控,这些特定调控因子在子宫内膜发育分化过程中呈现较为显著的时空表达特征,对内膜容受性形成有重要作用.相关细胞因子(白血病抑制因子、白细胞介素)、蛋白分子(胎盘蛋白、半乳糖凝集素-1)及特定转录因子(同源框基因)在子宫内膜容受性形成过程中伴随短暂、瞬间性高表达,其表达量为增生期的4～5倍,该时期与着床窗期时间一致,呈现出时空特异性.表明这几类生物活性分子可能与子宫内膜容受性形成密切相关.     

IL-1系统与胚泡着床的关系

<正>胚泡着床是成功妊娠的第一步,但其精确机制还不清楚.遗传学和分子生物学技术发展为着床的研究提供了新的手段.近年,人们从胚泡着床的分子机制方面进行了探索,细胞因子是一个引人注目的领域,其在着床中的作用日渐受到重视,其中白介素一1(Interleukin-l,IL-1)系统对胚泡着床的影响较大,研究资料较多,本文就近几年的文献作一综述.     

小鼠胚泡黏附时子宫内膜Galectin-1的变化

目的：探讨小鼠胚胎黏附时子宫内膜Galectin-1的变化。方法：双向聚丙烯酰胺凝胶电泳(2D-PAGE)分析妊娠d5小鼠胚泡黏附时着床点、着床旁子宫内膜总蛋白，以同龄未交配鼠子宫内膜为对照，差异蛋白质组学显示pⅠ约5．1、分子量约15ku的蛋白点在着床点、着床旁子宫内膜表达上调，且在着床点更明显。对此蛋白点用基质辅助激光解析电离飞行时间质谱测定其胶内酶解后的肽质量指纹谱(peptidemassfingerprint，PMF)。结果：Mascot：PMF在SWISS．PROT数据库查询为鼠源性Galectin．1。RT．PCR．~果显示d5孕小鼠子宫内膜Galectin．1mRNA水平也明显增加。结论：Galectil9．1可能参与胚泡着床这一重要生命活动过程。     

人子宫内膜细胞外基质在月经周期中变化的研究

本实验对人正常子宫内膜细胞外基质随月经周期的变动状况进行了观察，目的是进一步探讨为接受胚泡着床，子宫内膜的准备状态。子宫内膜标本利用ＬＳＡＢ免疫组织化学方法对细胞外基质的Ⅰ、Ⅲ、Ⅳ、Ⅴ型胶原蛋白、纤维粘连蛋白、层粘连蛋白在月经周期中的变化进行了观察。结果显示胶原蛋白、纤维粘连蛋白、层粘连蛋白主要分布在上皮组织的基膜中。胶原蛋白和纤维粘连蛋白总量在分泌早期明显减少。而层粘连蛋白总量在分泌期，特别在分泌中期明显增多。结果表明，细胞外基质随月经周期变化而明显变化。提示子宫内膜细胞外基质的周期变化对胚泡着床可能有着重要的作用。我们认为，细胞外基质是否能伴随月经周期而进行周期性变化是检查是否有正常月经周期的指标之一。本研究对着床、抗着床机理及某些不孕症的治疗将提供新方向。     

补肾活血方中药对妊娠大鼠子宫内膜容受性的影响

目的:观察补肾活血方中药对妊娠大鼠子宫内膜容受性的影响.方法:选用妊娠SD大鼠随机分为空白组、模型组和中药组,于妊娠第l天模型组和中药组大鼠皮下注射米非司酮溶液1次(米非司酮溶液5 g/L,5 mg/kg)造成胚泡着床障碍模型,空白组皮下注射生理盐水1次(1 mL/kg).空白组和模型组从妊娠第l天起予生理盐水灌胃(6.7 mL/kg),2次,d,连续5 d.中药组从妊娠第1天起行补肾活血方中药灌胃(7.6g生药/kg),2次,d,连续5d.于妊娠第5天扫描电镜观察各组子宫内膜胞饮突发育情况,逆转录聚合酶链反应(RT-PCR)检测子宫内膜整合素αvβ3mRNA的表达,于妊娠第10天计数各组大鼠胚泡着床数.结果:模型组子宫内膜表面未见明显的胞饮突发育,表现为增生早期的子宫内膜变化.中药组可见发育中的胞饮突,发育形态明显超前于模型组,接近于空白组;模型组αvβ3mRNA表达水平(0.854 5±0.0747,0.3984±0.093 7)显著低于空白组(1.051 8±0.087 8,0.601 6±0.133 8)(P<0.01),中药组αvβ3mRNA表达水平(0.987 6±0.075 1,0.539 6±0.058 4)显著高于模型组(P<0.05);模型组胚泡着床数(4.63±3.66)显著低于空白组(12.63±2.07)(P<0.01),中药组胚泡着床数(10.75±2.44)显著高于模型组(P<0.01).结论:补肾活血方中药能明显改善胚泡着床障碍大鼠子宫内膜表面胞饮突的发育,并显著提高子宫内膜整合素αvβ3mRNA的表达,有助于子宫内膜容受性的建立,从而最终提高胚泡的着床率.     

胚泡和内膜发育状态对子宫内膜“着床窗口”形成的影响

本文应用胚泡移植和改进的内膜上皮细胞与胚泡共培养方法研究了胚胎和子宫内膜不同发育状态对子宫内膜对胚泡接受性的影响.实验证明正常胚泡移植到子宫内膜的“着床窗口”出现时间以妊娠d4天上午9时到下午18时.如果被移植的胚泡是取自延缓着床胚泡,则它们的“着床窗口”出现时间有明显缩短,只能到下午14时为止.另外也证明.子宫内膜本身发育状态对内膜的接受性也有影响.以妊娠d5天内膜的胚泡附着数最多.所以.可以认为胚胎和内膜的发育状态都是可以影响内膜“着床窗口”的出现与消失的.     

Toll样受体4在宫腔粘连患者子宫内膜中的表达

目的:探讨Toll样受体4(TLR4)在宫腔粘连(IUAs)患者子宫内膜的表达。方法:选择2010年9月至2010年12月因IUAs在中南大学湘雅三医院行宫腔粘连分离术的患者75例。选择同期因不孕行宫腔镜检查且子宫内膜正常的非IUAs患者30例。术中获取子宫内膜,应用免疫组织化学方法检测TLR4在IUAs子宫内膜及非IUAs正常子宫内膜的表达。结果:(1)TLR4在IUAs子宫内膜、非IUAs正常子宫内膜中阳性表达率分别为97.3%、93.3%,两者比较差异有统计学意义(P<0.05),IUAs子宫内膜TLR4的阳性表达率高于非IUAs正常子宫内膜。(2)TLR4在重度、中度、轻度IUAs患者子宫内膜中的强阳性表达率分别为80%、40%、10%,两两比较均有统计学差异(P<0.05),TLR4的阳性表达随着粘连严重程度而增加。结论:TLR4表达强弱与粘连程度相关,随着粘连严重程度增加,TLR4表达逐渐增强,提示TLR4可能与宫腔粘连的发展有关。     

TRAIL在小鼠胚胎着床过程中子宫内膜的表达

目的:检测TRAIL在小鼠胚胎着床过程中子宫内膜的表达,探讨它在蜕膜细胞凋亡中的作 用。方法:采用RT-PCR及免疫组化技术检测妊娠d 1-8小鼠子宫组织TRAILmRNA及蛋白的表 达情况。结果:妊娠d 1-8的小鼠子宫组织均有TRAIL mRNA的表达,且着床期间的表达较着床前 明显增加(P<0．05)。妊娠d 1-3,小鼠子宫内膜无TRAIL蛋白表达;妊娠d 4,TRAIL表达在小鼠胚 胎定位、黏附点的子宫内膜腔上皮细胞;妊娠d 5-6,TRAIL定位于胚胎着床点附近的蜕膜细胞中; 妊娠d 7-8,TRAIL表达在与子宫蜕膜邻近的胚胎滋养层细胞中。结论:在小鼠胚胎着床过程中, TRAIL诱导子宫内膜腔上皮细胞凋亡可能是胚胎跨越上皮屏障的重要机制之一,且TRAIL诱导的 蜕膜细胞和胚胎滋养层细胞的凋亡在滋养层细胞对子宫内膜的适度侵入过程中起重要作用。     

Endometrial Dye Instillation: A Novel Approach to Histopathologic Evaluation of Morcellated Hysterectomy Specimens

The purpose of this prospective pilot case study was to determine whether instillation of trypan blue dye into the uterine cavity before laparoscopic hysterectomy and morcellation aids in gross identification of endometrium. The most common commercially available trypan blue stain, VisionBlue was used in this study. Instillation was performed at the beginning of the procedure using an embryo transfer catheter. A sterile solution of trypan blue, 0.5 mL, was instilled transcervically into the uterine cavities in 12 patients before laparoscopic hysterectomy with uterine morcellation. The morcellated specimens were sent for routine gross pathologic and histologic examination. It was concluded that intrauterine instillation of trypan blue stained the endometrium, thus aiding the pathologist in identification of the endometrium in morcellated uterine specimens.     

从子宫内膜的病理变化探讨宫内节育器引起出血的原因

本文观察了带不锈钢宫内节育器后引起出血的104例(50.96%的病例带器5年以上)子宫内膜的病理变化,以探讨出血的原因。子宫内膜主要的病理变化为慢性子宫内膜炎(53.85%),子宫内膜增生过长(19.23%),间质充血水肿(13.46%)。104例中40岁以上、带环5年以上的43例与同等条件的非因症取环的36例相对照,结果两组的慢性子宫内膜炎的发生率有显著差异(p<0.01);子宫内膜增生过长和间质充血、水肿的发生率无显著差异,因此认为带器出血可能与慢性子宫内膜炎有关。     

Enhanced endometrial response to a magnetic intrauterine device: A preliminary study

Objective?To evaluate the effects of an intrauterine device producing a static magnetic field on the endometrial histology of rats.

Methods?The experiments involved 20 adult female Wistar albino rats that were divided into five groups. Group 1 was sham-operated; Groups 2, 3 and 4 had a copper intrauterine device (IUD), an uncovered intrauterine magnet (IUM) or an intrauterine silicone-coated IUM, respectively, inserted into one of the uterine horns; in Group 5 an uncovered IUM was implanted subcutaneously. Six days later the rats were sacrificed; endometrial and subcutaneous tissues were harvested and examined microscopically.

Results?Copper IUDs caused classical cellular infiltration through the endometrium. IUMs, producing a static magnetic field, also caused leucocyte and monocyte infiltration of the endometrium and, in addition, a significant leucocyte accumulation over the endometrial surface.

Conclusion?This preliminary study reveals that an intrauterine magnet induces the accumulation of leucocytes in the uterine cavity in addition to the classic stromal infiltration caused by commercially available nonmagnetic IUDs. This activity could contribute to a greater efficacy of intrauterine contraception and should be investigated further.     

Hysteroscopy after uterine fibroid embolization in women of fertile age

AIM: Uterine artery embolization for fibroids is a controversial issue for women with incomplete reproductive plans. Ovarian failure and uterine infection are the most dreaded complications of this procedure. The purpose of the present study was to assess the types and the frequency of intrauterine abnormalities and the histological features of the endometrium after embolization. METHODS: Uterine artery embolization was performed on 51 women (average age 34.5 years) with intramural fibroid/s larger than 4 cm. Hysteroscopy and endometrial biopsy was performed from 3 to 9 months later in the luteal phase of the cycle. RESULTS: Despite all women having no major symptoms prior to hysteroscopy, only 19 (37%) had completely normal hysteroscopic findings. There was intrauterine protrusion of fibroid/s in 19 cases (37%), yellowish coloration of the endometrium in 14 (28%), intrauterine or cervical adhesions in seven (14%), and communication between the myoma and the uterine cavity in five cases (10%). A normal, functional endometrium was histologically verified in 44 women of 49 (90%) who could be evaluated. Regressive changes (necrosis or hyalinization) of leiomyoma or of indefinite origin were found in 17 patients and embolization particles in five, including one patient with microspheres inside the endometrial vessel. No case of Asherman syndrome or endometrial atrophy was observed. CONCLUSION: The frequency of abnormal hysteroscopic findings after embolization is surprisingly high. The clinical significance, reversibility, and impact on fertility of abnormal hysteroscopic findings after embolization remain unclear. Regardless, hysteroscopy should be strongly recommended to all patients after uterine fibroid embolization, prior to conception.     

Prediction of pregnancy after frozen‐thawed embryo transfer via in vivo intrauterine oxidation‐reduction potential measurements: a pilot study

Purpose

During the implantation period, the uterus goes through many complex, orchestrated changes, including alterations of the glycocalyx that are due to sialylation, sulfation, and fucosylation. A previous mouse study showed that the in vivo intrauterine oxidation‐reduction potential (ORP) aided in determining the alterations in the uterine endometrium that are suitable for implantation and for evaluating prospective uterine receptivity, while the in vivo intrauterine pH did not. It was assessed if the in vivo intrauterine ORP could be a useful parameter to predict pregnancy in women.

Methods

A prospective cohort study was conducted for patients who had received a frozen‐thawed single embryo transfer in a programmed, hormonally controlled cycle. The in vivo intrauterine ORP was measured 3 times during the treatment cycle, at cycle days 9‐10, 1 day before progesterone administration and immediately before the embryo transfer.

Results

The amount of in vivo intrauterine ORP at 9‐10 days after the start of menstrual bleeding was significantly lower in the pregnant group than in the non‐pregnant group. A receiver‐operator characteristic curve analysis of the intrauterine ORP as a predictor of non‐conception showed an area under the curve of 0.80.

Conclusion

The in vivo intrauterine ORP could be a useful parameter to predict pregnancy for the frozen‐thawed embryo transfer treatment cycle.     

Outpatient hysteroscopy in the diagnosis of neoplastic and preneoplastic lesions of the endometrium

The results of a study performed on a case series of 250 women treated in our out-patient department for abnormal uterine bleeding are reported. Half of these patients (125) were 45 years of age or over and therefore at risk of adenocarcinoma or endometrial hyperplasia while the other half were under 45 years of age. All the patients were submitted to hysteroscopic examination as out-patients (no important side-effects occurred), together with cytologic and/or histological examination of the endometrium. This procedure revealed no disease in 59 cases (23.6%) and the presence of one or more benign conditions in 188 patients (75.2%) (inflammation, polyposis, myomatosis, endocervical or uterine adenomiosis, endometrial hyperplasias, dysfunctional patterns, intrauterine foreign bodies). Endometrial adenocarcinoma was diagnosed in 3 patients (1.2%). The discovery of 3 cases (1.2%) of adenocarcinomas and 62 cases (24.8%) of endometrial hyperplasias (58 simple glandular hyperplasia, 3 cystic-glandular hyperplasias and 1 polypoid hyperplasia) emphasive the reliability of hysteroscopy in the diagnosis of endometrial neoplasias and their precursors.     

Intrauterine foreign bodies,other than contraceptive devices and systems,may affect fertility – Report of two very different cases

Abstract

Objectives To present two cases in which foreign bodies in the uterine cavity had a contraceptive effect for the duration of their presence in utero.

Case One case of endometrial osseous metaplasia and another case with unabsorbed suture material after a caesarean section resulted in foreign bodies acting like an intrauterine contraceptive. Ultrasound was used to diagnose the conditions, and hysteroscopy to remove the foreign bodies.

Conclusion Foreign intrauterine bodies should be considered in cases of infertility.     

Uterine contractility and embryo implantation

PURPOSE OF REVIEW: The aim of this article is to assess the importance of uterine contractility in the implantation of human embryos. RECENT FINDINGS: Recent findings show that the receptive phase of the endometrium seems to occur in close association with the appearance of pinopodes and endometrial integrins that may be activated by the IL-1 system. Throughout the menstrual cycle wavelike activity patterns of the uterus were identified with adequate wave patterns appearing to be related to successful reproduction in spontaneous cycles and in assisted reproduction. Such patterns are controlled by steroid hormones. Embryo attachment to the predecidualized endometrium and its invasion may be determined by the expression of proteolytic enzymes that require uterine quiescence for implantation. The uterine activity was detected both in vitro and in vivo by using invasive intrauterine pressure and noninvasive ultrasound approaches. Progesterone promotes local vasodilatation and uterine musculature quiescence by inducing nitric oxide synthesis in the decidua. At present, until new evidence emerges to demonstrate otherwise, the effects of progesterone are, directly or indirectly, the only determinant of endometrial preparation for embryo nidation, with the induction of uterine quiescence being one of these effects. SUMMARY: Adequate uterine contractility may provide for gamete/embryo transportation through the utero-tubal cavities and successful embryo implantation in spontaneous or assisted reproduction. Inadequate uterine contractility may lead to ectopic pregnancies, miscarriages, retrograde bleeding with dysmenorrhea and endometriosis.