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。     

抗层粘连蛋白-1抗体与子宫内膜异位症不孕

层粘连蛋白-1是存在于细胞外基质的主要成分,是细胞粘附于基质的重要介质。它在正常及异位的子宫内膜及胚胎滋养层均有表达。抗层粘连蛋白-1抗体是针对层粘连蛋白-1的自身抗体,由存在于异位内膜的层粘连蛋白-1抗原引起自身免疫反应所致。这种抗体引起在位子宫内膜的免疫病理损害,可能与子宫内膜异位症不孕及反复早期自然流产有关。     

细胞外基质与生殖

细胞外基质(ECM)主要包括纤维粘连蛋白(FN),层粘连蛋白(LN),胶原纤维(CL).三者在生殖过程中均起着重要作用.胶原又分为Ⅰ～Ⅴ型胶原,其中Ⅳ型胶原与生殖关系最密切.LN主要分布于基质与基底膜,FN主要于基质及间质细胞,而Ⅳ型胶原主要于基底膜.ECM主要功能为促进细胞间粘附与增殖,从而促进卵泡发育,孕卵种植及维持妊娠.ECM异常可导致流产、早产、胎膜早破、妊高征等病理妊娠.另外,ECM尚与妇科肿瘤关系密切.本文主要阐述了ECM与生殖的关系.     

细胞外基质与生殖

细胞外基质（ECM）主要包括纤维粘连蛋白（NF）,层粘连蛋白（LN）,胶原纤维（CL）。三者在生殖过程中均起重要作用。胶原又分为I－V型胶原,其中IV型胶原与生殖关系最密切。LN主要分布于基质与基底膜,FN主要于基质及间质细胞,而IV型胶原主要于基底膜。ECM主要功能为细胞间粘附与增殖,从而促进卵泡发育,孕卵种植及维持妊娠。ECM异常可导致流产、早产、胎膜早破、妊高征等病理妊娠。另外,ECM尚与妇科肿瘤关系密切。本文主要阐述了ECM与生殖的关系。     

子宫内膜整合素β_3和细胞外基质的变化及与不孕症的关系

对生育组３１例,原因不明不孕组３４例采用免疫组化方法检测整合素β３及细胞外基质纤维粘连蛋白（ＦＮ）、层粘连蛋白（ＬＮ）、Ⅳ型胶原纤维（ＣＬ）在分泌期子宫内膜上的表达,探讨其变化规律及在调控妊娠中的作用。结果显示整合素β３在生育组腺上皮细胞分泌中期出现,持续至分泌晚期,而不孕组分泌期无表达;细胞外基质在生育组分泌中期呈强表达,早期次之,晚期较弱;不孕组在分泌各期表达均高于生育组。结论认为整合素β３ＦＮ、ＬＮ和Ⅳ型ＣＬ在分泌期子宫内膜上呈周期性变化参与子宫内膜的功能变化及胚泡的着床环节,其异常表达可致着床失败而不孕。     

小鼠子宫腺的免疫功能评价

子宫腺是啮齿动物妊娠时出现的一种暂时性子宫结构,含有基质及血管成分,以及一种形态特殊、体积较大、带有颗粒的子宫腺细胞。子宫腺可能在妊娠时具有免疫学方面的作用,子宫腺细胞可能具有免疫活性。     

妊娠小鼠子宫内出现的一类特殊细胞──颗粒子宫腺细胞

在昆明种小白鼠的子宫内证实有一类具有特殊性的细胞一颗粒子宫腺细胞。该细胞具有如下特点：１．体积大，胞质内含耐淀粉酶消化的ＰＡＳ阳性颗粒；２．分布位置特殊，位于子宫系膜三角区和基蜕膜；３．具有孕期变化，孕早期出现，中期最多，后期减少，产后消失。该类细胞的出现及消失与妊娠过程同步，故作者认为其与妊娠关系密切。     

基质金属蛋白酶系统与子宫内膜

基质金属蛋白酶能降解大多数细胞外基质，子宫内膜周期性的变化与细胞外基质的水解和重建关系密切，就基质金属蛋白酶系统在子宫内膜的表达、调控、作用以及其与子宫内膜周期性变化、内膜异常出血关系的研究进展作一综述。     

妊娠滋养细胞疾病的肿瘤标志物及其研究进展

人绒毛膜促性腺激素 (ＨＣＧ)是目前公认的妊娠滋养细胞疾病 (ＧＴＤ)最重要的肿瘤标志物。随着对ＧＴＤ研究深入 ,不但对ＨＣＧ有了更深入认识 ,而且发现了一些有价值的新标志物 ,现将各标志物对ＧＴＤ的诊断与治疗意义做一综述。1　滋养细胞产生的激素、蛋白和酶正常妊娠时 ,晚期囊胚着床于子宫内膜后 ,滋养层迅速分裂增生 ,细胞滋养细胞 (ＣＴ)是绒毛表面的干细胞 ,直接分化为合体滋养细胞 (ＳＴ)和中间型滋养细胞 (ＩＴ)。ＩＴ浸润子宫蜕膜和子宫浅肌层 ,建立母 -胎循环并固定胎盘。ＳＴ是执行功能的细胞 ,可产生多种激素、蛋白和酶。Ｇ…     

表皮生长因子受体在妇科肿瘤中的应用

近年来的研究表明，表皮生长因子（ＥＧＦ）与表皮生长因子受体（ＥＧＦＲ）在肿瘤形成及胚胎发生等方面有着重要意义，目前来检测ＥＧＦＲ的方法有免疫组织化学染色法、酶联免疫吸附试验（ＥＬＩＳＡ）法、放射免疫法及放射自显影法等。在宫颈肿瘤、子宫内膜癌、卵巢肿瘤、乳腺癌、早期妊娠胎盘的合体滋养细胞中均发现有ＥＧＦＲ的过度表达，这各过度表达与肿瘤组织的生物学行为、预后滋养细胞的功能分化有密切的关系。     

The killing of mouse trophoblast cells by granulated metrial gland cells in vitro

Mouse placental cell preparations have been maintained in culture, and the types of cell that attached to the culture dish were classified according to morphological criteria. However, these morphological criteria were insufficient to determine from which trophoblast layer in the placenta all of the types of cell found in the cultures originated. Some placental cell preparations were co-cultured with granulated metrial gland (GMG) cells and these cultures were studied using time-lapse video. Various responses to contacts between GMG cells and trophoblast cells were observed. These responses included the killing of trophoblast cells by GMG cells.     

Granulated metrial gland cells in the mouse placenta

A study has been made of granulated metrial gland (GMG) cells and adjacent layer 1 cytotrophoblast in the labyrinthine placenta of the mouse. In those cellular associations in which both cell types appeared healthy with the light microscope, examination with the electron microscope identified features which may form part of the early stages in the interaction which can occur between GMG cells and some layer 1 trophoblast. These included microvillous processes from each cell forming an interdigitating network, a polarization of mitochondria in a GMG cell with interdigitating microvilli, platelets, and some GMG cells which appeared to form a specialized cell junction with a small lymphocyte. The latter observation indicates that a tripartite functional relationship may exist between lymphocytes, GMG cells and layer 1 labyrinthine trophoblast. In a quantitative analysis of GMG cells in the maternal blood spaces of placentae no significant differences in the numbers of GMG cells present in these spaces or involved in an interaction with layer 1 labyrinthine trophoblast were detected between inbred and outbred pregnancies. These results suggest that histocompatibility antigens are not significant factors in determining the frequency of interactions between GMG cells and trophoblast.     

The killing of rat placental cells by rat and mouse granulated metrial gland cells in vitro

Small round cells which migrated from explant cultures of rat metrial gland were identified as granulated metrial gland (GMG) cells. They contained large amounts of glycoprotein and displayed the leucocyte common antigen. Other cells which migrated from the explants were probably derived from the fibroblast-like stromal cells of the metrial gland. The asialo-GM1 antigen was found on rat GMG cells in culture and in cryostat sections of rat metrial gland. The rat GMG cells in culture exhibited locomotion and, when co-cultured with placental cells, made numerous contacts with the placental cells. A small number of these contacts (less than 1 per cent) were followed rapidly by the death of the placental cell. Mouse GMG cells which had migrated from explant cultures of mouse metrial gland were also co-cultured with rat placental cells. The migratory activity of the mouse GMG cells also involved numerous contacts being made with rat placental cells and a small number (less than 1 per cent) of these contacts were cytotoxic for the rat placental cells. The observations support previous suggestions that GMG cells are a type of killer cell. The cytotoxic activity of rat and mouse GMG cells against co-cultured rat placental cells is discussed in relation to the nature of the target molecule involved.     

Leucocyte membrane antigens on mouse granulated metrial gland cells

An indirect immunofluorescence technique has been used to study the expression of leucocyte membrane antigens on mouse granulated metrial gland (GMG) cells. GMG cells isolated from cultured metrial gland explants and GMG cells in cryostat sections of uterine implantation sites were examined. GMG cells were found to express both the asialo-GM1 antigen and the Thy-1 antigen. GMG cells did not express the Lyt-1, Lyt-2, Mac-1, L3T4 or IgM antigens. These results provide new evidence that GMG cells are a type of NK cell.     

Receptors for IgG2b on cells of the mouse metrial gland

Single cells prepared from metrial glands of mice killed at days 10, 13 and 17 of pregnancy were assayed for the expression of Fc gamma receptors in a standard rosetting assay using sheep red blood cells sensitised with a mouse monoclonal IgG2b antibody. Rosettes, indicating Fc gamma receptors, were found on both granulated metrial gland (GMG) cells and non-GMG cells, comprising mainly stromal cells, from each stage of pregnancy. Some animals were given an intravenous injection of horseradish peroxidase 2 h before they were killed in order to identify endocytic cells. No GMG cells were found to have endocytosed the horseradish peroxidase. Non-GMG cells which showed endocytic activity all expressed Fc gamma receptors but these receptors were also found on some of the non-GMG cells which had not exhibited endocytosis. The finding of Fc gamma receptors on GMG cells provides further evidence that these cells may be related to NK cells.     

Evaluation of the murine metrial gland for immunological function

The metrial gland (MG) is a transient uterine structure associated with rodent pregnancy. The gland is a complex structure consisting of stromal and vascular elements, as well as a population of histologically distinctive, large, granulated metrial gland (GMG) cells. The functions of the MG and of the GMG cells, as well as their relationship to the success of pregnancy, are unknown. Based upon morphological and morphometric studies it has been proposed that the MG might be involved in the immunology of pregnancy and that GMG cells could be immunocompetent. Explant cultures of MG have therefore been evaluated for immunological function. Lytic activity against the NK sensitive target cell line YAC and mitogen responsiveness could not be detected. MG tissue and medium conditioned by overnight culture of MG tissue (MG-CM) suppressed the response of murine spleen cells to Con A. MG-CM also reduced the lytic activity of splenic NK cells against YAC target cells. However, uptake of [3H]thymidine was elevated when YAC cells were cultured in MG-CM. The response of embryonic and uterine cells to growth in MG-CM was complex. MG-CM had little effect on isotope incorporation by decidual cells recovered at 6.5 days or by embryonic cells recovered from 12.5 day embryos. However, thymidine incorporation was less in MG-CM than in control medium for 12.5 day placental cells, 6.5 day embryonic sac, 6.5 day ectoplacental cone and 3.5 day blastocysts. Cytotoxicity and cytostasis accounted for reduced uptake of isotope in cultures of 3.5 day blastocysts and 6.5 day embryonic tissues. Loss of viability could not be detected in any other assays. Both YAC cells and unstimulated splenocytes showed altered morphology and improved viability when cultured in MG-CM. This study suggests that the only immunological role the MG might have during normal pregnancy is that of non-specific intra-uterine suppression. Alternatively, differential regulation of cell proliferation might be a function of the MG, within the pregnant uterus. The latter mechanism could also account for the apparent observation of non-specific immunosuppression.     

Light and electron microscopic study of epithelial cells from the human oviduct and uterus subcultured on extracellular matrix gel

OBJECTIVE: To investigate the structure of epithelial cells from the human oviduct and uterus on extracellular matrix (ECM) gel in the first passage. STUDY DESIGN: Human oviducts and endometrial tissues were obtained from patients undergoing total hysterectomy; the epithelial cells, having been isolated by enzyme digestion, were cultured on polystyrene plastic surfaces. The epithelial nature of the cells was confirmed by immunocytochemistry, and their morphology was examined by microscopy. Cells of an epithelial nature were then trypsinized and cultured on an ECM gel-coated filter insert for 5 days. The cells, in parallel with the tissues, were subsequently prepared for transmission electron microscopy. RESULTS: Plastic-cultured cells had no sign of differentiation and appeared as elongated spindle cells in sections. These cells looked columnar and highly polarized after being cultured on ECM gel surfaces. They were similar to epithelial cells from the corresponding tissue fragment. Cultured on ECM gel, the ciliated epithelial cells of human oviducts appeared ultrastructurally similar to glandular cells from the human uterus. Cilia did not form under culture conditions. CONCLUSIONS: It seems that human uterine and oviduct epithelial cells can acquire polarized morphology and differentiated states on ECM gel after having lost it on plastic surfaces and that ECM gel by itself is not enough to induce cilia formation in culture.     

A monoclonal antibody, 4H12, recognizes a surface antigen found on granulated metrial gland cells in the murine decidua

A monoclonal antibody (MAb), designated 4H12, was selected for reactivity to a surface antigen on PYS-2 teratocarcinoma cells. 4H12 was the product of a fusion of lymphoid cells of a non-immunized pregnant C57BL/6 mouse to NS-1 myeloma cells. Initial studies utilizing immunohistochemistry revealed that MAb 4H12 bound to an antigen found on cells in the decidua basalis of 7-, 8- and 10-day pregnant mice. Antigen-positive cells of 11--19-day pregnant mice were also found predominantly in the decidua. A few antigen-positive cells were found in the labyrinth of the placenta and up against Reichert's membrane. Antigen-positive cells were morphologically and spatially distinct, oval to round with large periodic acid Schiff positive granules. Indirect immunofluorescent (IIF) labeling of decidual cultures showed antigen on the surface of cells that were small, oval to round and adherent. The antigen recognized by MAb 4H12 was removed from tissue sections with trypsin and protease and therefore is suggested to be a protein. We conclude that MAb 4H12 recognizes a surface antigen found on cells historically described as granulated metrial gland (GMG) cells. This MAb should greatly facilitate the further analysis of the life history and function of GMG cells during pregnancy.