In vivo the extravillous trophoblasts (EVTs) penetrate the decidua and the first third of the myometrium to remodel the uterine spiral arteries and achieve the high-flow, low-resistance circulation characteristic of the intervillous space of the term placenta. Much of our understanding of these processes comes from histologic analysis of placental bed biopsies, a limited tissue source and one that can provide only a snapshot of a dynamic process. To better characterize these cellular interactions, we have developed an in vitro co-culture system in which first trimester villous explants are cultured at low oxygen tension in contact with 2-mm(2) sections of decidua parietalis from the same patient. Hematoxylin eosin counterstaining of paraffin sections shows that EVT columns form at the tips of the placental villi and adhere and penetrate the decidual surface. The decidual blood vessels in the path of the EVT show morphologic disruption. Immunohistochemical analysis of the co-cultures using both an endothelial specific anti-CD31 and an anti-smooth muscle actin antibody show a disruption of the integrity of the vessel lining together with a complete loss of organized smooth muscle actin surrounding the blood vessels. In contrast control decidua samples in the absence of placental villi exhibit blood vessels with a complete endothelial lining and an organized muscular sheath. Using both an anti-cytokeratin-7 and anti-Cdx-2 antibody specific to trophoblasts, we show that these changes coincide with invasion of the vessels by endovascular trophoblasts and penetration of the decidua by interstitial EVTs. No EVTs were found in the control decidua. Thus we conclude that this in vitro model mimics the physiologic change observed in vivo during trophoblast invasion into maternal decidual tissues, and as such it may provide useful information concerning the interactions between EVTs and decidual cells and vessels during early gestation.

中文翻译：

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滋养细胞介导的蜕膜血管重塑的新型体外模型。

在体内，绒毛外滋养细胞 (EVT) 穿透蜕膜和前三分之一的子宫肌层，重塑子宫螺旋动脉，实现足月胎盘绒毛间隙的高流量、低阻力循环特征。我们对这些过程的大部分理解来自胎盘床活检的组织学分析，这是一种有限的组织来源，只能提供动态过程的快照。为了更好地表征这些细胞相互作用，我们开发了一种体外共培养系统，在该系统中，妊娠早期的绒毛外植体在低氧张力下与来自同一患者的顶蜕膜的 2-mm(2) 部分接触进行培养。石蜡切片的苏木精伊红复染显示 EVT 柱在胎盘绒毛的尖端形成并粘附并穿透蜕膜表面。EVT 路径中的蜕膜血管表现出形态学破坏。使用内皮特异性抗 CD31 和抗平滑肌肌动蛋白抗体对共培养物进行的免疫组织化学分析显示，血管内壁的完整性遭到破坏，血管周围有组织的平滑肌肌动蛋白完全丧失。相比之下，在没有胎盘绒毛的情况下，对照蜕膜样本显示出具有完整内皮衬里和有组织的肌肉鞘的血管。使用滋养层细胞特异性抗细胞角蛋白 7 和抗 Cdx-2 抗体，我们表明这些变化与血管内滋养细胞侵入血管和间质 EVT 侵入蜕膜相一致。在对照蜕膜中未发现 EVT。因此，我们得出结论，这种体外模型模拟了在滋养细胞侵入母体蜕膜组织期间在体内观察到的生理变化，因此它可能提供有关 EVT 与蜕膜细胞和血管在早期妊娠期间相互作用的有用信息。