松弛素参与生理及病理妊娠的研究进展

松弛素(relaxin,RLX)是胰岛素超家族的一员,对维持正常妊娠和分娩具有重要作用。RLX主要由卵巢黄体分泌。RLX及其受体松弛素家族多肽受体1(relaxin family peptide receptor 1,RXFP1)广泛分布于卵巢、子宫内膜、蜕膜、胎盘和胎膜组织。RLX参与胚胎发育、乳腺和子宫发育、妊娠维持、宫颈成熟、分娩发动以及妊娠期间循环系统代偿等多环节。RLX表达异常与流产、早产、胎膜早破、妊娠期高血压疾病和胎儿生长受限等多种病理妊娠有关。RLX及其受体RXFP1是母胎免疫耐受细胞因子调控网络中的重要一环。目前已知RLX是一种多能效的激素,除生殖系统外,还在肝脏、肾脏、心脏、大脑等组织器官,参与复杂多样的病理生理调节,具有广阔的应用前景。综述RLX参与生理及病理妊娠的最新研究进展。     

整合素在生殖领域的研究进展

整合素是一类普遍存在于细胞表面的跨膜糖蛋白 ,属于细胞粘附分子的一大家族。它参与细胞与细胞、细胞与细胞外基质的相互作用 ,在许多生理、病理过程中起着重要的作用。研究表明 ,哺乳动物卵子、精子表面均表达整合素 ,与受精过程有关。在月经周期的不同时期 ,子宫内膜表面表达的整合素种类和数量均不同 ,特别在月经黄体中期 ,其表达有特殊的变化 ,表明与子宫内膜的容受性及受精卵的植入相关。另外 ,它在胚胎的生长发育、不孕、流产等过程中也起重要作用。现对整合素在生殖领域的研究进展作一综述     

钙粘附蛋白与子宫内膜

钙粘附蛋白全称钙依赖的粘附分子家族(cadherin),是一种单链跨膜糖蛋白,主要参与介导特定器官和组织同型细胞间的粘附.在月经周期不同阶段,钙粘附蛋白的表达量和类型不同,且受类固醇激素的调节.在胚泡着床过程中,不同类型的钙粘附蛋白分别在内膜上皮、间质及滋养细胞的表达,提示其在着床调节方面的重要作用.E-钙粘附蛋白结构、功能的缺陷与子宫内膜异位症发病的关系密切.     

钙粘附蛋白与子宫内膜

钙粘附蛋白全称钙依赖的粘附分子家族（cadherin)，是一种单链跨膜糖蛋白，主要参与介导特定器官和组织同型细胞间的粘附。在月经周期不同阶段，钙粘附蛋白的表达量和类型不同，且受类固醇激素的调节。在胚泡着床过程中，不同类型的钙粘附蛋白分别在内膜上皮、间质及滋养细胞的表达，提示其在着床调节方面的重要作用。E－钙粘附蛋白结构、功能的缺陷与子宫内膜异位症发病的关系密切。     

血小板激活因子在妊娠生理方面的研究进展

血小板激活因子（ｐｌａｔｅｌｅｔ－ａｃｔｉｖａｔｉｎｇｆａｃｔｏｒ，ＰＡＦ）是迄今发现的最强的血小板聚集剂及最强的血管活性物质之一，广泛存在于人体各种组织并在多种生理和病理过程起重要作用，在妊娠期间，与妊娠有关的组织如：子宫内膜，羊膜，胎儿等均可合成血小板激活因子并通过组织细胞膜上的特异性受体来发挥生物学效应，参与妊娠的多种生理过程，包括排卵，受精，孕卵着床，胎肺成熟及分娩等。     

子宫内膜局部肾素-血管紧张素系统

肾素．血管紧张素系统（renin-angiotensin system,RAS）是人体重要的体液调节系统,当这一系统出现紊乱易引发多种疾病。以往研究多偏重于全身RAS系统,近年来,局部RAS成为研究热点。子宫内膜相关研究表明,局部RAS参与子宫内膜周期性变化及生殖功能调节、维持妊娠期人体子宫稳态等一系列生理过程;并参与子宫内膜异位症、功能性子宫内膜出血、子宫内膜癌等病理生理过程。     

小鼠囊胚在子宫内膜体外共培养模型上着床的超微结构观察

目的:进一步证明已建立的体外着床模型的可行性。方法:将妊娠d4的小鼠囊胚培养在已建立的体外子宫内膜共培养模型上,电镜观察胚胎植入时囊胚与子宫内膜上皮细胞相互关系的超微结构。结果:小鼠囊胚能正常脱透明带、黏附和扩展。扫描电镜见黏附在子宫内膜上的囊胚呈椭圆形或扁平形;胚胎表面具微绒毛;在胚胎与子宫内膜细胞接触点可见胚胎滋养细胞黏附于胞饮突上。透射电镜观察显示,胚胎滋养细胞通过微绒毛黏附于上皮细胞上,有些滋养细胞通过微绒毛开始植入,局部滋养细胞与上皮细胞形成紧密连接。胚胎滋养细胞与上皮细胞间形成许多镶嵌连接。超微结构显示粗面内质网、线粒体、溶酶体和核糖体非常丰富。结论:小鼠囊胚在子宫内膜体外模型上生长发育良好,该胚胎与子宫内膜共培养系统是研究胚胎着床机理的理想体外模型。     

紧密连接蛋白claudin-4在子宫内膜异位症患者在位与异位内膜组织中的表达

目的 检测紧密连接蛋白claudin-4在正常子宫内膜、子宫内膜异位症(内异症)患者的在位和异位内膜组织中的表达,评价elaudin-4在内异症发病中的作用.方法 选择35例内异症患者的卵巢异位内膜组织(异位内膜组),其中27例内异症患者的在位子宫内膜(在位内膜组)和35例非内异症良性卵巢、子宫疾病患者(对照组)的子宫内膜组织.透射电镜观察各组内膜组织中紧密连接的形态学变化;免疫组化和免疫印迹法检测elaudin-4蛋白的表达量,RT-PCR技术检测claudin-4 mRNA的表达量.结果 (1)透射电镜下,异位内膜组内膜组织中紧密连接结构消失,胶原组织丰富;在位内膜组内膜组织中紧密连接的结构与对照组内膜组织相似,未见明显变化.(2)免疫组化检测结果显示,clandin-4蛋白的阳性染色主要定位于子宫内膜腺上皮细胞膜,异位内膜组织中claudin-4的阳性染色很弱甚至缺失;在对照组、在位内膜组和异位内膜组内膜组织中,claudin-4蛋白表达量分别为89±24、84±22、27±14;claudin-4 mRNA表达量分别为14.5±6.8、13.8±9.5、2.6±2.5.异位内膜组内膜组织中claudin-4 mRNA和蛋白的表达量均低于在位内膜组和对照组内膜,差异有统计学意义(P<0.05).在位内膜组和对照组内膜组织中claudin-4 mRNA和蛋白的表达量分别比较,差异均无统计学意义(P>0.05).结论 异位子宫内膜组织中clandin-4的低表达可能参与了内异症的发病.     

子宫内膜蜕膜化调节机制的研究现状

子宫内膜蜕膜化是子宫为了适应妊娠而做出的最早改变之一。围着床阶段,子宫内膜在生化、细胞、生理及功能等各个水平发生了复杂变化,使得自身具有可接受性,能为胚胎着床及生长提供合适的微环境。多种激素、细胞因子、转录因子、免疫细胞等参与调节子宫内膜间质细胞向蜕膜细胞的转变。     

体外实验中肝细胞生长因子诱导子宫内膜癌细胞的侵袭作用

肝细胞生长因子(hepatocyte growth factor,HGF)是一种多向生长因子,由成纤维细胞和其他间叶细胞所分泌。其受体Met是一种跨膜的酪氨酸激酶受体,主要由上皮细胞表达。已有研究表明,在许多人体组织包括子宫内膜中,HGF与Met之间的相互作用可调节细胞的增殖和运动;HGF还可以调节组织的再生与修复,如月经期后子宫内膜的再生;此外,HGF/Met与肿瘤浸润有关,在体外实验中HGF可刺激多种恶性肿瘤细胞系的浸润功能,并与某些     

Alterations in tight junctions of human endometrial epithelial cells during normal menstrual cycle--freeze-fracture electron microscopic study

The structural change in the tight junction between human endometrial epithelial cells during the normal menstrual cycle was observed by means of freeze-fracture replica electron microscopy. Tight junctions between epithelial cells of the endometrial basal layer showed no alterations in structure during the menstrual cycle, while those between epithelial cells of the functional layer exhibited remarkable changes synchronized with the menstrual cycle; in the early proliferative phase, the tight junctions were composed of strands running mainly parallel to the luminal surface and the depth of the junctions from the luminal surface was 0.57 +/- 0.04 micron (Mean +/- S.E.), whereas in the late proliferative phase the junction formed a prominent network of strands 0.80 +/- 0.04 micron deep. In the early secretory phase, the junctions developed mostly as a complex network, and the depth was 0.96 +/- 0.04 micron. In the late secretory phase, the network consisting of the junctions looked disorderly and the depth of the junctions was reduced to 0.71 +/- 0.04 micron. As a conclusion, it was suggested that the tight junction in the human endometrial epithelium tended to develop or diminish according to the phase of the menstrual cycle.     

Ultrastructural study of the intercellular junction and lanthanum penetration in the mouse blastocyst

Cell junctions in mouse blastocyst were ultrastructurally investigated with or without lanthanum tracer. Tight junctions, gap junctions and desmosomes were observed in the trophectoderm. The tight junction was located near the zona pellucida in all trophoblast interspaces, whereas the gap junction and the desmosome, which were infrequently observed, were localized far from the zona pellucida. However, the desmosomes in the trophectoderm of the expanded blastocyst after culture increased in number and came to be located near the zona pellucida. The trophoblast layer excluded lanthanum whose invasion was interrupted by the tight junction. There were a few intermediate junctions in the interspace between the trophoblast and the inner cell mass cell as well as between the inner cell mass cells. These findings indicate that a substances whose molecular weight exceeds that of lanthanum (138.9) may not flow into the blastocyst through the intercellular space. Moreover, it is speculated that the intercellular connection is strengthened during the expansion of the blastocyst.     

Tight junction formation in epithelial ovarian adenocarcinoma

BACKGROUND: Epithelial cells are characterised by their ability to form polarised cell sheets with barriers between two tissue compartments. Epithelial tightness and apical/basolateral orientation are maintained through adherens and tight junctions (TJs). Alterations in junction formation and function could promote tumorigenesis via increased access to growth factors and cytokines. The etiology and development of epithelial ovarian cancer (EOC) are far from understood. The ovarian surface epithelium (OSE), regarded as progenitor cells of EOC, form weak functional TJs in culture without expressing typical junction proteins. However, these integral membrane epithelial proteins, E-cadherin, claudin-3 and claudin-4, are often found in EOC. METHODS: To clarify whether EOC can form functional TJs, 4 different ovarian cancer cell lines of various histology were analysed for their expression of TJ (claudin-1, claudin-3, claudin-4 and zonola occludens-1 (ZO-1)) and adherens junction (AJ) (E-cadherin and N-cadherin) proteins, and the ability to build up trans-epithelial resistance (TER) in culture was measured. RESULTS: We found expression for all cell-junction proteins with a typical honeycomb-staining pattern in the serous adenocarcinomas indicating proper junction formation. Clear-cell and endometrioid adenocarcinomas showed a different expression pattern. By measuring TER, including Ca(2+) switch experiments, functional TJs were shown to build up only in serous adenocarcinomas. CONCLUSION: Serous adenocarcinomas formed functional TJs in vitro. The presence of claudin-4 might be essential for the function of TJs in ovarian cancer.     

胚胎着床过程中子宫内膜细胞表面吞饮泡及细胞连接的变化

本文简要叙述了胚胎着床过程中子宫内膜表面桥粒、吞饮泡、紧密连接、间隙连接以及基膜等与胚胎着床紧密相关的细胞表面形态学结构在着床过程中发生的一系列变化及其可能的作用 ,这些结构变化有时可作为着床的标志性特征     

上皮-间质转化在子宫腺肌病中作用的研究进展

子宫腺肌病(ADS)是子宫内膜腺体及间质侵入子宫肌层导致的以子宫局灶或弥漫性增大为主要改变的良性疾病,其具体发病机制尚不清楚。目前多数研究者认为ADS是基底层内膜细胞增生、侵入到肌层间质的结果。在上皮-间质转化(EMT)过程中,上皮细胞失去细胞极性,细胞间紧密连接和黏附连接减弱,获得了浸润性和游走迁移能力,成为具有间质细胞功能和特性的细胞。EMT在肿瘤形成中赋予细胞迁移、浸润的能力,而ADS发生、发展过程中子宫内膜细胞侵入肌层的生物学行为与之非常相似。已有研究表明EMT在ADS形成中具有重要作用。目前ADS的临床治疗面临较多的挑战,因此阐明ADS的发生机制是寻求临床早期预防、治疗ADS有效方法的关键。     

Increased expressions of claudin-1 and claudin-7 during the progression of cervical neoplasia

OBJECTIVES: Claudin proteins represent a large family of integral membrane proteins crucial for tight junction formation and function and they have been shown to be expressed differently in various cancers. We investigated whether the expressions of claudin-1 and claudin-7 are associated with the progression of uterine cervical neoplasia. METHODS: We analyzed 89 formalin-fixed paraffin embedded cervical tissues that included 10 normal cervical epithelium, 19 low-grade squamous intraepithelial lesion (LSIL), 20 high-grade squamous intraepithelial lesion (HSIL), 20 invasive squamous cell carcinoma (ISCC) without lymph node (LN) metastasis, and 20 ISCC with LN metastasis. The expressions of claudin-1 and claudin-7 were determined by immunohistochemistry. RESULTS: The expressions of claudin-1 and claudin-7 were undetectable in normal cervical squamous epithelium, but had variable staining in the basal layer of normal endocervical glands. The expressions of both proteins, mainly as membranous staining, gradually increased in accordance with the progression from LSIL to HSIL and ISCC (both P values are <0.001) and were detected in all cases of ISCC. CONCLUSIONS: These results suggest that claudin-1 and claudin-7 may play a significant role in tumor progression of cervical neoplasia and may represent useful markers for malignant transformation of cervical squamous cells. Further studies would likely result in the development of novel approaches for early detection and therapy for this disease.     

睾丸支持细胞连接结构在精子发生过程的作用

睾丸支持细胞(Sertoli cell)是曲细精管内唯一与生精细胞直接接触的体细胞,在生精过程中起免疫屏障、支持、营养和调节作用。相邻支持细胞、支持细胞与生精细胞之间的连接类型包括紧密连接、锚定连接和缝隙连接。这些连接结构与精子发生过程紧密联系,连接结构紊乱或异常,会干扰精子发生过程中的信号通路、生精细胞迁移、精子形态形成和精子极性维持等,引起生精功能障碍,导致男性生育力下降,甚至不育。     

Adhesion Molecules in Human Trophoblast – A Review. II. Extravillous Trophoblast

At the tips of anchoring villi, cytotrophoblast (CTB) proliferation leads to a process of multilayering in which cells lose their attachment to the villous basement membrane and develop into columns, within which they adhere to one another using desmosomes, with associated intermediate filament bundles. Non-desmosomal cadherins, tight junction proteins and other adhesion molecules are also present, suggesting that actin-associated adhesions contribute to placental anchorage. In the distal columns, cell–cell interactions diminish, cells upregulate β1 integrins and bind to a provisional fibrinoid extracellular matrix, eventually detaching to migrate into the decidual stroma and myometrium, where interstitial and endovascular extravillous trophoblast (EVT) populations show distinct repertoires of adhesion molecules.