Inhibition of vascular endothelial growth factor/vascular permeability factor action blocks estrogen-induced uterine edema and implantation in rodents
Inhibition of vascular endothelial growth factor/vascular permeability factor action blocks estrogen-induced uterine edema and implantation in rodents
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DOI：
10.1095/biolreprod.102.006700
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发表时间：
2002-12-01
影响因子：
3.6
通讯作者：
Koos, RD
中科院分区：
文献类型：
--
作者：
Rockwell, LC;Pillai, S;Koos, RD
雌激素诱导啮齿动物子宫微血管通透性迅速增加，导致间质水肿，子宫湿重明显增加。这种水肿被认为为子宫内膜的生长和重塑创造了一个最佳的环境，为着床和怀孕做准备。子宫内膜微血管通透性增加也与着床同时发生。雌激素诱导的子宫水肿发生之前，血管内皮生长因子（VEGF）的表达立即增加，VEGF是微血管通透性的有效刺激物。本研究的目的是确定VEGF免疫中和对a)雌二醇诱导的子宫水肿和b)妊娠的干扰程度。在第一组实验中，未成熟雌性大鼠在17 -雌二醇治疗前注射VEGF抗血清或正常兔血清（NRS）。雌二醇单独处理的大鼠在6 h时子宫湿重比对照组增加57%。注射200或300毫升的VEGF抗血清，其反应分别仅比对照组降低20%和10%。在第二组实验中，年轻成年雌性小鼠在交配后第4天的1200 h分别给予100毫升的VEGF抗血清或NRS。经nrs治疗的小鼠妊娠正常。然而，VEGF抗血清完全阻断妊娠。当VEGF抗血清治疗的雌性小鼠在第5天检查植入部位时，没有发现植入部位。这些结果表明，a) VEGF是雌激素诱导的子宫血管通透性增加的主要媒介，b) VEGF诱导的水肿是植入发生的绝对必要条件。
Estrogen induces a rapid increase in microvascular permeability in the rodent uterus, leading to stromal edema and a marked increase in uterine wet weight. This edema is believed to create an environment optimal for the growth and remodeling of the endometrium in preparation for implantation and pregnancy. Increased endometrial microvascular permeability also occurs in conjunction with implantation. Estrogen-induced uterine edema is immediately preceded by an increase in the expression of vascular endothelial growth factor (VEGF), a potent stimulator of microvascular permeability. The objective of this study was to determine to what degree immunoneutralization of VEGF would interfere with a) estradiol-induced uterine edema and b) pregnancy. In the first set of experiments, immature female rats were injected with either VEGF antiserum or normal rabbit serum (NRS) prior to 17beta-estradiol treatment. Rats treated with estradiol alone showed a 57% increase in uterine wet weight at 6 h compared with controls. Injection of 200 or 300 mul of VEGF antiserum reduced the response to only 20% and 10% above controls, respectively. In the second set of experiments, young adult female mice were treated with 100 mul of either VEGF antiserum or NRS at 1200 h on the fourth day after mating. NRS-treated mice had normal pregnancies. VEGF antiserum, however, completely blocked pregnancy. When VEGF antiserum-treated females were examined on Day 5 for the presence of implantation sites, none were found. These results show that a) VEGF is the major mediator of estrogen-induced increase in uterine vascular permeability and b) VEGF-induced edema is absolutely essential for implantation to take place.