Ovarian hyperstimulation syndrome (OHSS) is one of the most serious and iatrogenic complications that can occur during in vitro fertilization treatment. Although the pathogenesis of OHSS is not fully understood, vascular endothelial growth factor (VEGF) has been recognized as an important mediator of the development of OHSS. Transforming growth factor-beta-1 (TGF-β1) is known to regulate various ovarian functions. However, whether VEGF can be regulated by TGF-β1 in human granulosa cells has not been determined. In addition, the role of TGF-β1 in the pathogenesis of OHSS remains unknown. In the present study, we demonstrate that TGF-β1 stimulates VEGF expression in and secretion from both immortalized human granulosa-lutein (hGL) cells and primary hGL cells. Our results demonstrate that the SMAD2/3, ERK1/2, and p38 MAPK signaling pathways are involved in TGF-β1-induced VEGF expression and secretion. Using a mouse OHSS model, we show that the expression levels of TGF-β1 and VEGF are increased in the ovaries of OHSS mice. Blocking TGF-β1 signaling inhibits the development of OHSS by attenuating VEGF expression. Moreover, clinical results reveal that the protein levels of TGF-β1 and VEGF are increased in the follicular fluid of patients with OHSS, and that the levels of these two proteins in the follicular fluid are positively correlated. The results of this study help to elucidate the mechanisms by which VEGF expression is regulated in hGL cells, which could lead to the development of alternative therapeutic approaches for treating OHSS.

中文翻译：

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TGF-β1诱导人颗粒-叶黄素细胞中的VEGF表达：卵巢过度刺激综合征发病机制的潜在机制。

卵巢过度刺激综合症（OHSS）是在体外受精治疗期间可能发生的最严重的医源性并发症之一。尽管尚未完全了解OHSS的发病机理，但血管内皮生长因子（VEGF）被认为是OHSS发生的重要介质。已知转化生长因子-β-1（TGF-β1）调节各种卵巢功能。然而，尚未确定在人颗粒细胞中VEGF是否可以被TGF-β1调节。另外，TGF-β1在OHSS的发病机理中的作用仍然未知。在本研究中，我们证明TGF-β1刺激永生化的人类颗粒-叶黄素（hGL）细胞和原代hGL细胞中的VEGF表达和分泌。我们的结果表明，SMAD2 / 3，ERK1 / 2，p38和MAPK信号通路与TGF-β1诱导的VEGF表达和分泌有关。使用小鼠OHSS模型，我们显示OHSS小鼠卵巢中TGF-β1和VEGF的表达水平增加。阻断TGF-β1信号传导通过减弱VEGF表达来抑制OHSS的发展。而且，临床结果表明，OHSS患者的卵泡液中TGF-β1和VEGF的蛋白水平升高，并且卵泡液中这两种蛋白的水平呈正相关。这项研究的结果有助于阐明在hGL细胞中调节VEGF表达的机制，这可能导致开发替代的治疗OHSS的治疗方法。我们表明，OHSS小鼠卵巢中TGF-β1和VEGF的表达水平升高。阻断TGF-β1信号传导通过减弱VEGF表达来抑制OHSS的发展。而且，临床结果表明，OHSS患者的卵泡液中TGF-β1和VEGF的蛋白水平升高，并且卵泡液中这两种蛋白的水平呈正相关。这项研究的结果有助于阐明在hGL细胞中调节VEGF表达的机制，这可能导致开发替代的治疗OHSS的治疗方法。我们表明，OHSS小鼠卵巢中TGF-β1和VEGF的表达水平升高。阻断TGF-β1信号传导通过减弱VEGF表达来抑制OHSS的发展。而且，临床结果表明，OHSS患者的卵泡液中TGF-β1和VEGF的蛋白水平升高，并且卵泡液中这两种蛋白的水平呈正相关。这项研究的结果有助于阐明在hGL细胞中调节VEGF表达的机制，这可能导致开发替代的治疗OHSS的治疗方法。临床结果显示，OHSS患者的卵泡液中TGF-β1和VEGF的蛋白水平升高，并且卵泡液中这两种蛋白的水平呈正相关。这项研究的结果有助于阐明在hGL细胞中调节VEGF表达的机制，这可能会导致开发替代的治疗OHSS的治疗方法。临床结果显示，OHSS患者的卵泡液中TGF-β1和VEGF的蛋白水平升高，并且卵泡液中这两种蛋白的水平呈正相关。这项研究的结果有助于阐明在hGL细胞中调节VEGF表达的机制，这可能导致开发替代的治疗OHSS的治疗方法。