VEGFR-1 blockade disrupts peri-implantation decidual angiogenesis and macrophage recruitment.
VEGFR-1 blockade disrupts peri-implantation decidual angiogenesis and macrophage recruitment.
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DOI：
10.1186/2045-824x-6-16
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Shawber CJ
中科院分区：
文献类型：
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作者：
Douglas NC;Zimmermann RC;Tan QK;Sullivan-Pyke CS;Sauer MV;Kitajewski JK;Shawber CJ
血管生成和巨噬细胞募集到子宫是子宫去个体化的关键特征；黄体酮介导的子宫变化，使胚胎着床和怀孕开始。在目前的研究中，我们表征了血管内皮生长因子受体-1 （VEGFR-1）在巨噬细胞和着床周子宫内皮细胞中的表达，并确定了VEGFR-1的功能是否需要蜕膜血管生成、巨噬细胞募集和/或妊娠的建立。免疫组化法检测子宫内皮细胞和巨噬细胞中VEGFR-1的表达。为了评估持续阻断VEGFR-1的效果，成年雌性小鼠每3天给予VEGFR-1阻断抗体MF-1，持续18天。6次给药后，雌性进行交配，在胚胎第3.5天给药。胚胎第7.5天定量内皮细胞和巨噬细胞。在胚胎7.5天和10.5天分析妊娠情况。F4/80+巨噬细胞遍布间质，胚胎着床前在子宫内膜腔和腺体附近大量存在，着床后分散在蜕膜中。VEGFR-1的表达仅限于子宫内皮细胞。F4/80+巨噬细胞常与原发性蜕膜区VEGFR-1+内皮细胞相邻。持续的VEGFR-1阻断与蜕膜血管和巨噬细胞密度的显著降低相关，但不影响胚胎着床或维持妊娠直至胚胎10.5天。我们发现，VEGFR-1在妊娠期蜕膜血管生成和巨噬细胞向着床部位募集中都起作用。VEGFR-1由内皮细胞表达，然而阻断内皮细胞中VEGFR-1的功能导致巨噬细胞向子宫募集减少。VEGFR-1阻断不影响妊娠的建立和/或维持。
Angiogenesis and macrophage recruitment to the uterus are key features of uterine decidualization; the progesterone-mediated uterine changes that allow for embryo implantation and initiation of pregnancy. In the current study, we characterized the expression of vascular endothelial growth factor receptor-1 (VEGFR-1) in macrophages and endothelial cells of the peri-implantation uterus and determined if VEGFR-1 function is required for decidual angiogenesis, macrophage recruitment, and/or the establishment of pregnancy. Expression of VEGFR-1 in uterine endothelial cells and macrophages was determined with immunohistochemistry. To assess the effect of continuous VEGFR-1 blockade, adult female mice were given VEGFR-1 blocking antibody, MF-1, every 3 days for 18 days. After 6 doses, females were mated and a final dose of MF-1 was given on embryonic day 3.5. Endothelial cells and macrophages were quantified on embryonic day 7.5. Pregnancy was analyzed on embryonic days 7.5 and 10.5. F4/80+ macrophages are observed throughout the stroma and are abundant adjacent to the endometrial lumen and glands prior to embryo implantation and scatter throughout the decidua post implantation. VEGFR-1 expression is restricted to the uterine endothelial cells. F4/80+ macrophages were often found adjacent to VEGFR-1+ endothelial cells in the primary decidual zone. Continuous VEGFR-1 blockade correlates with a significant reduction in decidual vascular and macrophage density, but does not affect embryo implantation or maintenance of pregnancy up to embryonic day 10.5. We found that VEGFR-1 functions in both decidual angiogenesis and macrophage recruitment to the implantation site during pregnancy. VEGFR-1 is expressed by endothelial cells, however blocking VEGFR-1 function in endothelial cells results in reduced macrophage recruitment to the uterus. VEGFR-1 blockade did not compromise the establishment and/or maintenance of pregnancy.