The differences of mechanisms between normal luteal formation and occurrence of ovarian hyperstimulation syndrome

血管内皮生长因子（Vascular endothelial growth factor， VEGF）具有促进内皮细胞生长和血管通透性的作用。据报道，在正常黄体形成过程中，卵巢中VEGF的表达也会增加。本研究探讨卵巢过度刺激综合征（OHSS）的发生机制。与假妊娠大鼠的黄体相比，OHSS模型大鼠卵巢中VEGF和VEGF受体(R)的表达受到极大刺激。Evans蓝法检测OHSS大鼠卵巢血管通透性明显增加。促性腺激素释放激素激动剂（GnRHa）处理可阻断OHSS大鼠卵巢VEGF-VEGFR表达和血管通透性的增加。内皮细胞紧密连接蛋白在血管通透性中起关键作用。由于已知有几种紧密连接蛋白，我们检查了这些蛋白在OHSS大鼠卵巢中的表达。卵巢OHSS大鼠的Claudin-5和occludin蛋白明显降低。然而，GnRHa处理阻断了这两种蛋白的减少。此外，我们的临床经验表明，在GnRHa的延续可以防止体外受精和胚胎移植过程中OHSS的发生。综上所述，推测由VEGF-VEGFR过度表达导致的claudin-5和occludin的表达降低是由正常黄体形成转变为OHSS发生的原因。

Vascular endothelial growth factor(VEGF) is well known to stimulate both the growth of endothelium and vascular permeability. VEGF expression in the ovary is also reported to increase during normal luteal formation. In this study we investigated the mechanisms of the occurrence of ovarian hyperstimulation syndrome(OHSS).The expression of VEGE and VEGF receptors(R) was extremely stimulated in the ovaries of OHSS rat models compared with corpora lutea of pseudopregnant rats. Vascular permeability examined with Evans blue was markedly increased in the ovaries of OHSS rats. Gonadotropin releasing hormone agonist(GnRHa) treatment blocked the increase of VEGF-VEGFR expression and vascular permeability of the ovaries of OHSS rats.Tight junction proteins of endothelium are reported to play a pivotal role in vascular permeability. As there are known to be several sorts of tight junction proteins, we checked the expression of such proteins in the ovaries of OHSS rats.Claudin-5 and occludin protein were significantly decreased in the ovaries OHSS rats. However, GnRHa treatment blocked the decrease in both proteins. Moreover, we clinically experienced that the continuation at GnRHa prevented the occurrence of OHSS during in vitro fertilization and embryo transfer.In summary, the decreased expression of claudin-5 and occludin caused by excess expression of VEGF-VEGFR was speculated to change from normal luteal formation into the occurrence of OHSS.