Cytotrophoblast induction of arterial apoptosis and lymphangiogenesis in an in vivo model of human placentation
Cytotrophoblast induction of arterial apoptosis and lymphangiogenesis in an in vivo model of human placentation
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DOI：
10.1172/jc127306
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发表时间：
2006-10-01
影响因子：
15.9
通讯作者：
Fisher, Susan J.
中科院分区：
文献类型：
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作者：
Red-Horse, Kristy;Rivera, Jose;Fisher, Susan J.
我们通过将胎盘绒毛移植到Scid小鼠的第五乳腺脂肪垫或肾包膜下，研究了体内侵入性人类细胞滋养层细胞的血管效应。在3周内，在两个位置都观察到了强大的细胞滋养层浸润。乳房脂肪垫的结构允许详细分析细胞与驻留的鼠血管的相互作用，其揭示了在小动脉的内皮细胞和平滑肌壁中的细胞凋亡的特异性诱导。这一发现，并在体外共培养模型的结果确认，表明一个平行的过程是重要的，使细胞滋养层血管内入侵在人类妊娠。肾实质的细胞滋养层侵入伴随着强烈的淋巴管生成反应，而在体外，细胞通过VEGF家族成员、FGF和TNF-α的作用刺激淋巴管内皮细胞迁移。免疫定位分析显示，人类妊娠与蜕膜淋巴管生成有关，因为淋巴管不是非妊娠子宫内膜的突出特征。因此，胎盘触发了蜕膜淋巴循环的发展，我们认为这在维持妊娠期间的液体平衡中起着重要作用，可能影响母胎免疫细胞的运输。
We studied the vascular effects of invasive human cytotrophoblasts in vivo by transplanting placental villi to the fifth mammary fat pads or beneath the kidney capsules of Scid mice. Over 3 weeks, robust cytotrophoblast invasion was observed in both locations. The architecture of the mammary fat pad allowed for detailed analysis of the cells' interactions with resident murine blood vessels, which revealed specific induction of apoptosis in the endothelial cells and smooth muscle walls of the arterioles. This finding, and confirmation of the results in an in vitro coculture model, suggests that a parallel process is important for enabling cytotrophoblast endovascular invasion during human pregnancy. Cytotrophoblast invasion of the kidney parenchyma was accompanied by a robust lymphangiogenic response, while in vitro, the cells stimulated lymphatic endothelial cell migration via the actions of VEGF family members, FGF, and TNF-alpha. Immunolocalization analyses revealed that human pregnancy is associated with lymphangiogenesis in the decidua since lymphatic vessels were not a prominent feature of the nonpregnant endometrium. Thus, the placenta triggers the development of a decidual lymphatic circulation, which we theorize plays an important role in maintaining fluid balance during pregnancy, with possible implications for maternal-fetal immune cell trafficking.