Crocker Ian P, Wareing Mark, Ferris Glenn R, Jones Carolyn J, Cartwright Judith E, Baker Philip N, Aplin John D
Maternal and Fetal Health Research Centre, University of Manchester, St Mary's Hospital, Manchester, UK.
J Pathol. 2005 Aug;206(4):476-85. doi: 10.1002/path.1801.
Extravillous trophoblasts (EVTs) invade and remodel uterine spiral arteries. Regulatory factors may include inherent vessel susceptibility, local oxygen levels and tumour necrosis factor alpha (TNFalpha). We have used an in vitro model to investigate interstitial and endovascular invasion of myometrial spiral arteries from pregnant and non-pregnant uteri and also omental arteries. To model endovascular invasion, fluorescent-labelled EVTs were perfused into the lumen of these dissected vessels. For interstitial invasion, labelled EVTs were layered on top. Cultures were either maintained in 17% or 3% oxygen, or cultured with TNFalpha. The invasion of arteries from pregnant women occurred via both routes at 17% oxygen, with endovascular invasion more efficient than interstitial. In omental arteries and spiral arteries from non-pregnant women, endovascular invasion was limited. Endovascular and interstitial invasion were lower in all arteries at 3% oxygen. Typically, endovascular events were clustered, with an associated disruption in the adjacent endothelium and smooth muscle. A role for TNFalpha in limiting invasion was also supported. In conclusion, priming of uterine arteries may be necessary prior to EVT invasion. Oxygen is a sensitive regulator within this physiological model and increased invasion at higher pO2 may explain the homing of EVT to maternal arteries rather than veins. Adequate vascular transformation may therefore rely on a balance between vascular receptivity, oxygen partial pressure, and exposure to inflammatory mediators.
绒毛外滋养层细胞（EVT）侵入并重塑子宫螺旋动脉。调节因子可能包括血管自身易感性、局部氧水平和肿瘤坏死因子α（TNFα）。我们使用体外模型研究了来自妊娠和非妊娠子宫的肌层螺旋动脉以及网膜动脉的间质和血管内侵入情况。为模拟血管内侵入，将荧光标记的EVT灌注到这些解剖血管的管腔中。对于间质侵入，将标记的EVT铺在血管顶部。培养物分别维持在17%或3%的氧浓度下，或与TNFα一起培养。在17%氧浓度下，来自孕妇的动脉通过两种途径发生侵入，血管内侵入比间质侵入更有效。在非孕妇的网膜动脉和螺旋动脉中，血管内侵入有限。在3%氧浓度下，所有动脉的血管内和间质侵入均较低。通常，血管内事件成簇发生，伴有相邻内皮和平滑肌的相关破坏。TNFα在限制侵入中的作用也得到了支持。总之，在EVT侵入之前，子宫动脉的启动可能是必要的。在这个生理模型中，氧是一个敏感的调节因子，较高的pO2时侵入增加可能解释了EVT归巢到母体动脉而非静脉。因此，充分的血管转化可能依赖于血管接受性、氧分压和炎症介质暴露之间的平衡。
