Hemochorial Placentation in the Primate: Expression of Vascular Endothelial Growth Factor, Angiopoietins, and Their Receptors Throughout Pregnancy1
Hemochorial Placentation in the Primate: Expression of Vascular Endothelial Growth Factor, Angiopoietins, and Their Receptors Throughout Pregnancy1
复制标题
灵长类动物的血脉胎盘：妊娠期间血管内皮生长因子、血管生成素及其受体的表达1
作者：
C. Wulff;H. Wilson;S. Dickson;S. Wiegand;H. Fraser
摘要 血管发育及其转化是血绒毛膜胎盘成功形成所必需的，血管内皮生长因子（VEGF）、血管生成素及其受体可能参与该过程的分子调控。为了确定这些假定的调节因子在广泛研究的灵长类动物（普通狨猴）中的潜在作用，我们使用原位杂交、Northern印迹分析和免疫细胞化学研究了它们在整个怀孕期间胎盘中的mRNA表达和蛋白质位置。 VEGF 定位于蜕膜细胞和细胞滋养层细胞，且在母体蜕膜中表达最高。 Flt 受体仅在合体滋养层中检测到，并且从第 10 周到足月胎盘中的表达增加。可溶性 Flt (sFlt) 也可通过 Northern 印迹分析检测到。 KDR 受体表达仅限于胎盘早期的间充质细胞和胎盘后期的胎儿胎盘脉管系统。 KDR 表达在整个怀孕期间增加。血管生成素-1 (Ang-1) 定位于合胞体滋养层，在妊娠后半期高度表达。 Ang-2 mRNA 仅定位于母体内皮细胞，并在 10 周胎盘中高表达。 Tie-2 受体存在于细胞滋养层细胞以及胎儿和母体血管中。在 14 周、17 周和足月胎盘的绒毛膜血管壁中检测到高 Tie-2 水平。这些结果表明，滋养层侵袭、母体血管转化以及胎儿胎盘血管分化和发育的过程受到血管生成配体-受体对的特异性作用的调节。具体来说，1) VEGF/Flt 和 Ang-1/Tie-2 可能促进滋养层生长，2) VEGF/KDR 和 Ang-1/Tie-2 可能支持胎儿胎盘血管发育和稳定，3) sFlt 可能平衡 VEGF 作用，4) Ang-2/Tie-2 可能重塑母体脉管系统。
Abstract Vascular development and its transformation are necessary for successful hemochorial placentation, and vascular endothelial growth factor (VEGF), angiopoietins, and their receptors may be involved in the molecular regulation of this process. To determine the potential role of these putative regulators in a widely studied primate, the common marmoset, we investigated their mRNA expression and protein location in the placenta throughout pregnancy using in situ hybridization, Northern blot analysis, and immunocytochemistry. VEGF was localized in decidual and cytotrophoblast cells, and its highest expression was found in the maternal decidua. The Flt receptor was exclusively detected in the syncytial trophoblast with increasing expression in placentae from 10 wk to term. Soluble Flt (sFlt) was also detectable by Northern blot analysis. KDR receptor expression was restricted to mesenchymal cells during early placentation and to the fetoplacental vasculature during later placentation. KDR expression increased throughout pregnancy. Angiopoietin-1 (Ang-1) was localized in the syncytial trophoblast, being highly expressed in the second half of gestation. Ang-2 mRNA localized exclusively to maternal endothelial cells, and was highly expressed in 10-wk placentae. The Tie-2 receptor was found in cytotrophoblast cells and in fetal and maternal vessels. High Tie-2 levels were detected in the wall of chorion vessels at 14-wk, 17-wk, and term placentae. These results suggest that the processes of trophoblast invasion, maternal vascular transformation, and fetoplacental vascular differentiation and development are regulated by the specific actions of angiogenic ligand-receptor pairs. Specifically, 1) VEGF/Flt and Ang-1/Tie-2 may promote trophoblast growth, 2) VEGF/KDR and Ang-1/Tie-2 may support fetoplacental vascular development and stabilization, 3) sFlt may balance VEGF actions, and 4) Ang-2/Tie-2 may remodel the maternal vasculature.
影响因子：
56.9
作者：
Suri, C;McClain, J;Yancopoulos, GD
通讯作者：
Yancopoulos, GD