GnRH Agonist Triggering Modulates PEDF to VEGF Ratio Inversely to hCG in Granulosa Cells
GnRH Agonist Triggering Modulates PEDF to VEGF Ratio Inversely to hCG in Granulosa Cells
复制标题
DOI：
10.1210/jc.2015-2312
复制
发表时间：
2015-11-01
影响因子：
5.8
通讯作者：
Ben-Ami, Ido
中科院分区：
文献类型：
--
作者：
Miller, Irit;Chuderland, Dana;Ben-Ami, Ido
内容：促性腺激素释放激素激动剂（GnRH-a）触发与辅助生殖技术周期中与人绒毛膜促性腺激素（hCG）相比，卵巢过度刺激综合征（OHSS）的风险降低有关。我们已经证明卵巢色素上皮衍生因子（PEDF），一种有效的抗血管生成因子，可以抵消血管内皮生长因子（VEGF）的表达，并且OHSS与hCG诱导的PEDF/VEGF比值受损相关。目的：本研究的目的是探讨促性腺激素释放激素-α触发是否可以直接调节颗粒细胞中PEDF/VEGF的平衡。设计：本研究的设计是一个小鼠模型和培养的颗粒细胞。主要结果：PEDF和VEGF的变化，通过定量PCR和Western blot分析。OHSS的症状记录在体重和腹膜血管渗漏的变化，量化的修改Miles vascular permeability assay.Results：促性腺激素释放激素-a刺激显着增加PEDF和降低VEGF的mRNA和蛋白水平都在大鼠颗粒细胞系和人原代颗粒细胞在体外。促性腺激素释放激素-α和人绒毛膜促性腺激素（hCG）在人颗粒细胞中触发PEDF mRNA和蛋白水平的逆转。在GnRH-a触发小鼠模型中，我们显示PEDF与VEGF比率的增加与体外结果相似。与hCG触发的小鼠相反，OHSS易感小鼠在GnRH-a触发后没有出现OHSS参数。最后，促性腺激素释放激素-a触发OHSS易感小鼠卵巢PEDF VEGF的比例显着增加与hCG触发的小鼠和control mice.Conclusions：促性腺激素释放激素-a触发诱导的PEDF/VEGF的平衡在颗粒细胞的直接影响，与hCG相反。我们的研究结果表明，一个新的阐明促性腺激素释放激素介导的OHSS的风险降低，并可能澄清这种触发方法的利弊。
Context: GnRH agonist (GnRH-a) triggering is associated with a reduced risk of ovarian hyperstimulation syndrome (OHSS) compared with human chorionic gonadotropin (hCG) in assisted reproduction technology cycles. We have shown that ovarian pigment epithelium derived factor (PEDF), a potent antiangiogenic factor, counteracts vascular endothelial growth factor (VEGF) expression and that OHSS is correlated with hCG-induced impaired PEDF to VEGF ratio.Objective: The objective of the study was to explore whether GnRH-a triggering could directly modulate PEDF/VEGF balance in granulosa cells.Design: The design of the study was a mouse model and cultured granulosa cells.Main Outcome: Changes in PEDF and VEGF were measured by quantitative PCR and Western blot analysis. OHSS symptoms were recorded by changes in body weight and in peritoneal vascular leakage, quantified by the modified Miles vascular permeability assay.Results: GnRH-a stimulation significantly increased PEDF and decreased VEGF mRNA and protein levels both in rat granulosa cell line and human primary granulosa cells in vitro. GnRH-a and hCG triggering inversely modulated PEDF mRNA and protein level in human granulosa cells in vivo. In the GnRH-a triggering mouse model, we showed similar increase in PEDF to VEGF ratio as in the in vitro results. OHSS-predisposed mice did not develop OHSS parameters after GnRH-a triggering, opposed to hCG-triggered mice. Finally, GnRH-a triggering of OHSS-predisposed mice significantly increased ovarian PEDF to VEGF ratio compared with hCG-triggered mice and control mice.Conclusions: GnRH-a triggering induces a direct effect on PEDF/VEGF balance in granulosa cells inversely to hCG. Our results suggest a novel elucidation to the GnRH-a triggering-mediated risk reduction of OHSS and may clarify the pros and cons of this triggering method.