Levin E R, Rosen G F, Cassidenti D L, Yee B, Meldrum D, Wisot A, Pedram A
Department of Medicine, the Long Beach Veterans Hospital, Long Beach, California 90822, USA.
J Clin Invest. 1998 Dec 1;102(11):1978-85. doi: 10.1172/JCI4814.
Controlled ovarian hyperstimulation with gonadotropins is followed by Ovarian Hyperstimulation Syndrome (OHSS) in some women. An unidentified capillary permeability factor from the ovary has been implicated, and vascular endothelial cell growth/permeability factor (VEGF) is a candidate protein. Follicular fluids (FF) from 80 women who received hormonal induction for infertility were studied. FFs were grouped according to oocyte production, from group I (0-7 oocytes) through group IV (23-31 oocytes). Group IV was comprised of four women with the most severe symptoms of OHSS. Endothelial cell (EC) permeability induced by the individual FF was highly correlated to oocytes produced (r2 = 0.73, P < 0.001). Group IV FF stimulated a 63+/-4% greater permeability than FF from group I patients (P < 0. 01), reversed 98% by anti-VEGF antibody. Group IV fluids contained the VEGF165 isoform and significantly greater concentrations of VEGF as compared with group I (1,105+/-87 pg/ml vs. 353+/-28 pg/ml, P < 0. 05). Significant cytoskeletal rearrangement of F-actin into stress fibers and a destruction of ZO-1 tight junction protein alignment was caused by group IV FF, mediated in part by nitric oxide. These mechanisms, which lead to increased EC permeability, were reversed by the VEGF antibody. Our results indicate that VEGF is the FF factor responsible for increased vascular permeability, thereby contributing to the pathogenesis of OHSS.
一些女性在使用促性腺激素进行控制性卵巢过度刺激后会出现卵巢过度刺激综合征（OHSS）。卵巢中一种未明确的毛细血管通透性因子被认为与此有关，血管内皮细胞生长/通透性因子（VEGF）是一种候选蛋白。对80名因不孕症接受激素诱导治疗的女性的卵泡液（FF）进行了研究。根据卵母细胞生成情况将卵泡液分组，从第一组（0 - 7个卵母细胞）到第四组（23 - 31个卵母细胞）。第四组由四名OHSS症状最严重的女性组成。单个卵泡液诱导的内皮细胞（EC）通透性与产生的卵母细胞高度相关（r2 = 0.73，P < 0.001）。第四组卵泡液刺激产生的通透性比第一组患者的卵泡液高63±4%（P < 0.01），抗VEGF抗体可使其降低98%。第四组卵泡液含有VEGF165异构体，与第一组相比，VEGF浓度显著更高（1105±87 pg/ml对353±28 pg/ml，P < 0.05）。第四组卵泡液导致F - 肌动蛋白显著重排形成应力纤维，以及ZO - 1紧密连接蛋白排列破坏，部分由一氧化氮介导。这些导致内皮细胞通透性增加的机制可被VEGF抗体逆转。我们的结果表明，VEGF是卵泡液中导致血管通透性增加的因子，从而促成了OHSS的发病机制。
