Development of cytotrophoblast columns from explanted first-trimester human placental villi:: Role of fibronectin and integrinα5β1
Development of cytotrophoblast columns from explanted first-trimester human placental villi:: Role of fibronectin and integrinα5β1
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DOI：
10.1095/biolreprod60.4.828
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发表时间：
1999-04-01
影响因子：
3.6
通讯作者：
Vicovac, L
中科院分区：
文献类型：
--
作者：
Aplin, JD;Haigh, T;Vicovac, L
我们观察到，人类妊娠早期漂浮间充质绒毛移植到I型胶原或Matrigel凝胶上后，锚定位点会重新发育。这些细胞包括细胞滋养层细胞柱，由茎绒毛细胞滋养层细胞增殖形成，通过整片显微镜和薄切片显微镜显示，并将溴脱氧尿苷掺入DNA中。在琼脂糖外植的组织中，未观察到柱状结构的形成。在Matrigel上，发育中的柱状细胞向下渗透到基质中，而在胶原I上，细胞滋养细胞片在凝胶表面扩散并合并形成一个外壳。发育中的柱状细胞滋养细胞上调整合素α 1 β 1和α 5 β 1，并产生含有癌胎纤维连接蛋白的细胞外基质，与体内一样。功能阻断抗体用于研究整合素-纤维连接蛋白相互作用在胶原蛋白上锚定绒毛发育中的作用。在24 h添加针对纤维连接蛋白和整合素亚基α 5和β 1的抗体，都改变了细胞滋养层生长的模式，抗纤维连接蛋白导致细胞在细胞滋养层内形成圆形，并增加了其周围的单细胞数量。抗整合素5引起外植体内细胞的四舍五入和重新分布。在抗整合素β 1的存在下，薄片内的细胞-胶原相互作用不稳定，通常导致周围出现细胞聚集的环形。这些结果表明：1)间充质绒毛至少在妊娠早期结束前仍具有形成锚定位点的潜力；2)与允许的细胞外基质的粘附刺激细胞滋养细胞沿外膜谱系增殖和分化；3)整合素α - 5 β - 1-纤维连接蛋白的相互作用显著促进胎盘与子宫细胞外基质的锚定。我们认为，随着发育中的胎盘分叉，每当外周绒毛接触蜕膜时，新的锚定位点就会形成。预计这一过程有助于胎盘-蜕膜界面的稳定性。
Human first-trimester floating mesenchymal villi explanted onto gels of collagen I or Matrigel were observed to undergo de novo development of anchoring sites. These consisted of cytotrophoblast columns that formed by proliferation of stem villous cytotrophoblast cells, as revealed by whole-mount and thin-section microscopy and incorporation of bromodeoxyuridine into DNA. Column formation occurred exclusively at the distal tips of the villi, No column formation was observed in tissue explanted onto agarose. On Matrigel, the developing columns penetrated downwards into the matrix, whereas on collagen I, cytotrophoblast sheets spread across the surface of the gel and merged to form a shell, The developing columnar cytotrophoblast up-regulated integrins alpha 1 beta 1 and alpha 5 beta 1 and produced an extracellular matrix containing oncofetal fibronectin, as in vivo. Function-blocking antibodies were used to investigate the role of the integrin-fibronectin interaction in anchoring villus development on collagen I. Antibodies to fibronectin and the integrin subunits alpha 5 and beta 1, added at 24 h, all changed the pattern of cytotrophoblast outgrowth, Anti-fibronectin caused cell rounding within the cytotrophoblast sheet and increased the population of single cells at its periphery. Anti-integrin alpha 5 caused rounding and redistribution of cells within the outgrowth. In the presence of anti-integrin beta 1, cell-collagen interactions within the sheet were destabilized, often leading to the appearance of an annulus of aggregated cells at the periphery. These results show that 1) mesenchymal villi retain the potential to form anchoring sites until at least the end of the first trimester, 2) adhesion to a permissive extracellular matrix stimulates cytotrophoblast proliferation and differentiation along the extravillous lineage, 3) integrin alpha 5 beta 1-fibronectin interactions contribute significantly to anchorage of the placenta to uterine extracellular matrix. We suggest that as the developing placenta ramifies, new sites of anchorage form whenever peripheral villi contact decidua. This process is predicted to contribute to the stability of the placental-decidual interface.