Degradation of extracellular matrix by mouse trophoblast outgrowths: a model for implantation.
Degradation of extracellular matrix by mouse trophoblast outgrowths: a model for implantation.
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DOI：
10.1083/jcb.96.4.1108
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发表时间：
1983-04
期刊：
影响因子：
--
通讯作者：
Werb Z
中科院分区：
文献类型：
--
作者：
Glass RH;Aggeler J;Spindle A;Pedersen RA;Werb Z
在植入过程中，胚胎附着在子宫内膜表面，滋养层穿过子宫上皮，锚定在子宫结缔组织中。为了确定滋养层是否可以通过降解正常子宫细胞外基质的成分来促进子宫的侵袭，将小鼠胚泡培养在含有糖蛋白、弹性蛋白和胶原的放射性标记的细胞外基质上。胚胎附着在基质上，滋养层遍布表面。从培养第5天开始，标记的肽释放到培养基中。胚胎从基质中释放的放射性肽的分子量从25，000以上到200以上不等。到第7天，存在单个滋养层细胞彼此分离的区域，暴露出清除了基质的下层基质。在第8天用NH（4）OH溶解滋养层细胞时，很明显滋养层生长物下面的区域已经清除了基质。扫描电子显微镜和延时电影显微摄影证实，基质的消化是高度本地化的，只发生在滋养层下面，没有证据表明基质的消化超出了滋养层生长的外围。观察到的退化的尖锐边界可能是由于滋养层的局部蛋白酶分泌，滋养层表面的膜蛋白酶，或内吞作用。基质的消化不依赖于纤溶酶原，因此排除了纤溶酶原激活剂的作用。消化不受各种激素和抑制剂的抑制，包括孕酮、17β-雌二醇、亮抑酶肽、EDTA、秋水仙碱、氯化铵或ε-氨基己酸。这种在细胞外基质上培养胚胎的系统可能有助于确定在胚胎发育过程中调节滋养层迁移和侵入母体组织的过程。
During implantation the embryo attaches to the endometrial surface and trophoblast traverses the uterine epithelium, anchoring in the uterine connective tissue. To determine whether trophoblast can facilitate invasion of the uterus by degrading components of normal uterine extracellular matrix, mouse blastocysts were cultured on a radio-labeled extracellular matrix that contained glycoproteins, elastin, and collagen. The embryos attached to the matrix, and trophoblast spread over the surface. Starting on day 5 of culture there was a release of labeled peptides into the medium. The radioactive peptides released from the matrix by the embryos had molecular weights ranging from more than 25,000 to more than 200. By day 7 there were areas where individual trophoblast cells had separated from one another, revealing the underlying substratum that was cleared of matrix. When trophoblast cells were lysed with NH(4)OH on day 8, it was apparent that the area underneath the trophoblast outgrowth had been cleared of matrix. Scanning electron microscopy and time-lapse cinemicrography confirmed that the digestion of matrix was highly localized, taking place only underneath the trophoblast, with no evidence of digestion of the matrix beyond the periphery of the trophoblast outgrowth. The sharp boundaries of degredation observed may be due to localized proteinase secretion by trophoblast, to membrane proteinases on the surface of trophoblast, or to endocytosis. Digestion of the matrix was not dependent on plasminogen, thus ruling out a role for plasminogen activator. Digestion was not inhibited by a variety of hormones and inhibitors, including progesterone, 17β-estradiol, leupeptin, EDTA, colchicine, NH(4)Cl, or ε-aminocaproic acid. This system of culturing embryos on extracellular matrix may be useful in determining the processes that regulate trophoblast migration and invasion into the maternal tissues during implantation.0