Preovulatory treatment of mice with anti-VEGF receptor 2 antibody inhibits angiogenesis in corpora lutea.
Preovulatory treatment of mice with anti-VEGF receptor 2 antibody inhibits angiogenesis in corpora lutea.
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DOI：
10.1006/mvre.2001.2312
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发表时间：
2001-07
影响因子：
3.1
通讯作者：
R. Zimmermann;T. Hartman;Peter Bohlen;M. Sauer;Jan Kitajewski
中科院分区：
文献类型：
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作者：
R. Zimmermann;T. Hartman;Peter Bohlen;M. Sauer;Jan Kitajewski
成年哺乳动物的血管生成主要发生在雌性生殖器官：卵巢和子宫。黄体形成过程中血管生成非常活跃。血管生成的关键调节因子是血管内皮生长因子（VEGF），它在黄体形成过程中高度表达。抑制 VEGF 活性可以通过阻止血管生成来阻断黄体的形成和功能。 VEGF 受体 2 (VEGF-R2) 介导 VEGF 的血管生成作用，并在黄体形成过程中表达。我们假设用抗 VEGF-R2 抗体治疗会通过阻断 VEGF/VEGF-R2 相互作用来抑制黄体血管生成。用 PMSG/hCG 诱导未成熟小鼠超排卵，导致黄体新生血管形成，内皮特异性粘附分子 PECAM 的丰富染色证明了这一点。对未成熟小鼠施用多剂量的抗 VEGF-R2 (DC101) 单克隆抗体。在用 PMSG/hCG 诱导超数排卵前 2 天开始治疗。该抗体抑制黄体血管生成，黄体中心缺乏 PECAM 染色即可证明。在给予促性腺激素之前开始用抗体进行多剂量治疗不能将黄体抑制与发育卵泡中血管生成抑制的后果分开。给予单次排卵前剂量的抗VEGF-R2抗体，使得卵泡血管生成不会受到影响，也抑制黄体发育，表明黄体血管生成是黄体发育所必需的。我们得出的结论是，VEGF 通过 VEGF-R2 发挥作用，在黄体血管生成和黄体形成中具有必然的作用。
Adult mammalian angiogenesis occurs predominantly in female reproductive organs: the ovary and the uterus. Angiogenesis is very active during corpus luteum formation. A key regulator of angiogenesis is vascular endothelial growth factor (VEGF), which is highly expressed during corpus luteum formation. Inhibition of VEGF activity can block the formation and function of the corpora lutea by preventing angiogenesis. The VEGF receptor 2 (VEGF-R2) mediates the angiogenic action of VEGF and is expressed during corpus luteum formation. We hypothesized that treatment with an antibody against VEGF-R2 would inhibit luteal angiogenesis by blocking VEGF/VEGF-R2 interaction. Immature mice were induced to superovulate with PMSG/hCG resulting in neovascularization in the corpora lutea, as evidenced by abundant staining for the endothelial-specific adhesion molecule PECAM. Multiple doses of a monoclonal antibody against the VEGF-R2 (DC101) were administered to immature mice. Treatment was initiated 2 days prior to the induction of superovulation with PMSG/hCG. This antibody inhibited luteal angiogenesis as evidenced by the lack of PECAM staining in the center of the corpora lutea. Multiple dose treatment with antibody initiated prior to gonadotropin administration could not dissociate the luteal inhibition from the consequences of inhibition of angiogenesis in the developing follicle. Administration of a single, preovulatory dose of anti-VEGF-R2 antibody, such that follicular angiogenesis would not be affected, also inhibited luteal development, demonstrating that luteal angiogenesis is required for corpus luteal development. We conclude that VEGF acting through VEGF-R2 has an obligatory role in luteal angiogenesis and corpus luteum formation.