Endokrinologikum Hamburg, 20251 Hamburg, Germany.
Hum Reprod. 2010 Apr;25(4):862-73. doi: 10.1093/humrep/dep468. Epub 2010 Jan 29.
Extensive invasion of the maternal decidua by extravillous trophoblast is considered of critical importance for implantation and placentation in humans, the decidua being viewed as a passively invaded tissue. In this study, we examined whether decidual cells might contribute to the highly dynamic processes at the fetal-maternal interface by active movement.
Primary endometrial stromal cells (ESCs) or the telomerase-immortalized ESC line, St-T1b, was induced to decidualize or was left undifferentiated. The AC-1M88 cell line served as a model for extravillous trophoblast cells. Motility of ESCs and trophoblast cells was monitored in transwell invasion and migration assays under co-culture conditions. Secretion of matrix metalloproteinases (MMPs) was assessed by gelatin zymography.
AC-1M88 cell invasiveness was unaffected by the presence of ESCs, irrespective of their decidualization status. Surprisingly, decidualized ESCs were significantly more invasive than undifferentiated cells, and this invasive activity was strongly enhanced when cells were cultured in direct contact with AC-1M88 cells. Conditioned medium from AC-1M88 cells also stimulated migration and invasion of ESCs. Secretion of MMP-2 and -9 by ESCs was increased upon decidualization.
Enhanced motility and invasive capacity of decidualized ESCs in the presence of trophoblastic cells lead us to hypothesize a major contribution of the decidua in encapsulating the early conceptus and supporting subsequent trophoblast invasion. Our findings thus suggest a far more active role of the decidua in the implantation process than hitherto recognized.
滋养层细胞外突广泛侵入母体蜕膜被认为对人类着床和胎盘形成至关重要,蜕膜被视为被动入侵组织。在这项研究中,我们通过主动运动来研究蜕膜细胞是否可能通过主动运动对胎儿-母体界面的高度动态过程做出贡献。
原代子宫内膜基质细胞(ESCs)或端粒酶永生化 ESC 系 St-T1b 被诱导分化为蜕膜细胞或保持未分化状态。AC-1M88 细胞系作为滋养层细胞外突的模型。在共培养条件下,通过 Transwell 侵袭和迁移实验监测 ESCs 和滋养层细胞的迁移能力。通过明胶酶谱法评估基质金属蛋白酶(MMPs)的分泌。
无论 ESCs 是否分化为蜕膜细胞,AC-1M88 细胞的侵袭能力都不受影响。令人惊讶的是,与未分化细胞相比,分化的 ESCs 具有更强的侵袭能力,当细胞与 AC-1M88 细胞直接培养时,这种侵袭活性得到了强烈增强。来自 AC-1M88 细胞的条件培养基也刺激了 ESCs 的迁移和侵袭。ESCs 分泌 MMP-2 和 MMP-9 的能力在蜕膜化后增加。
在滋养层细胞存在的情况下,分化的 ESCs 运动性和侵袭能力增强,这使我们假设蜕膜在包裹早期胚胎和支持随后的滋养层细胞侵袭方面具有重要作用。因此,我们的研究结果表明,蜕膜在着床过程中的作用比以往认识的更为积极。