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/jci27306
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发表时间：
2006-10
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影响因子：
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通讯作者：
K. Red-Horse;J. Rivera;A. Schanz;Yan Zhou;V. Winn;Mirhan Kapidzic;E. Maltepe;K. Okazaki;R. Koch
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文献类型：
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作者：
K. Red-Horse;J. Rivera;A. Schanz;Yan Zhou;V. Winn;Mirhan Kapidzic;E. Maltepe;K. Okazaki;R. Koch
我们通过将胎盘绒毛移植到Scid小鼠的第5乳腺脂肪垫或肾囊下，在体内研究了侵袭性人细胞滋养细胞对血管的影响。3周后，在两个部位观察到强大的细胞滋养细胞侵袭。乳腺脂肪垫的结构允许对细胞与常驻小鼠血管的相互作用进行详细分析，这揭示了小动脉内皮细胞和平滑肌壁的细胞凋亡的特异性诱导。这一发现，以及在体外共培养模型中证实的结果，表明一个平行的过程对于人类怀孕期间细胞滋养细胞血管内侵袭是重要的。细胞滋养细胞对肾实质的侵袭伴随着强大的淋巴管生成反应，而在体外，细胞通过VEGF家族成员、FGF和tnf - α的作用刺激淋巴内皮细胞迁移。免疫定位分析显示，人类妊娠与蜕膜中的淋巴管生成有关，因为淋巴管不是未妊娠子宫内膜的显著特征。因此，胎盘触发蜕膜淋巴循环的发育，我们推测蜕膜淋巴循环在维持妊娠期间体液平衡方面起着重要作用，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.