sRAGE downregulates the VEGF expression in OHSS ovarian granulosa cells

Abstract

Objective

Ovarian hyperstimulation syndrome (OHSS) is mainly caused by human chorionic gonadotropin (hCG) through vasoactive mediators such as vascular endothelial growth factor (VEGF) and various inflammatory factors. Our previous study showed that soluble receptor for advanced glycation end products (sRAGE) played a protective role in PCOS by inhibiting VEGF, so wanted to explore the role of sRAGE in OHSS.

Methods

Two sets of experiments were performed in this study. In part one, sRAGE protein levels in follicular fluid (FF) samples from 60 patients with OHSS and 60 non-OHSS patients were measured by ELISA. In part two, ovarian granulosa cells were isolated from an additional 25 patients with OHSS and cultured. Then, ovarian granulosa cells were treated with different concentrations of sRAGE. Granulosa cells cultured without sRAGE stimulation were used as the control group. The levels of VEGF, amphiregulin (AREG), betacellulin (BTC), and epiregulin (EREG) mRNA were examined by quantitative RT-PCR. The protein levels of VEGF, AREG, BTC, and EREG were measured by ELISA.

Results

Compared with non-OHSS patients, patients with OHSS exhibited lower sRAGE levels in both serum and FF (p < .05). Treatment with sRAGE decreased the production of VEGF, and the effects were dependent on the concentration of sRAGE (p < .05). Simultaneously, the expression of the EGF-like growth factors AREG, BTC and EREG was decreased, and their expression was dependent on the concentration of sRAGE (p < .05).

Conclusions

sRAGE downregulate VEGF expression in OHSS ovarian granulosa cells, in which EGF-like growth factor pathway may be involved, and sRAGE may play a potential protective role in OHSS.

sRAGE下调OHSS卵巢颗粒细胞中VEGF的表达 摘要

目的：卵巢过度刺激综合征（Ovarian hyperstimulation syndrome, OHSS）主要由人绒毛膜促性腺激素（human chorionic gonadotropin, hCG）引起, 通过血管内皮生长因子（vascular endothelial growth factor, VEGF）和各种炎症因子等血管活性介质起作用。我们之前的研究表明, 可溶性晚期糖基化终产物受体（soluble receptor for advanced glycation end products, sRAGE）通过抑制VEGF在PCOS中发挥保护作用, 因此希望探讨sRAGE在OHSS中的作用。

方法：本研究进行了两组实验。第一部分, 采用ELISA法测定60例OHSS患者和60例非OHSS患者卵泡液（follicular fluid, FF）样本中sRAGE蛋白水平。第二部分, 从另外25例OHSS患者中分离卵巢颗粒细胞并进行培养。然后用不同浓度的sRAGE处理卵巢颗粒细胞。未经sRAGE刺激培养的颗粒细胞作为对照组。通过定量RT-PCR检测VEGF、双调素（amphiregulin, AREG）、β细胞素（betacellulin, BTC）和表皮调节素（epiregulin, EREG）mRNA的水平。ELISA法检测VEGF、AREG、BTC和EREG的蛋白水平。

结果：与非OHSS患者相比, OHSS患者血清和FF中sRAGE水平均较低（p<0.05）。sRAGE治疗可降低VEGF的生成, 其效果取决于sRAGE的浓度（p<0.05）。同时, EGF样生长因子AREG、BTC和EREG的表达降低, 且其表达取决于sRAGE的浓度（p<0.05）。

结论：sRAGE下调OHSS卵巢颗粒细胞VEGF的表达, EGF样生长因子途径可能参与其中, sRAGE可能在OHSS中起到潜在的保护作用。

Keywords:

• OHSS
• sRAGE
• VEGF
• EGF-like growth factors
• granulosa cells

Acknowledgment

The language corrections in this study were made with the help of American Journal Experts (AJE).

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Third Affiliated Hospital of Zhengzhou University.

Informed Consent

All authors have read and approved the final version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The dataset supporting the conclusions of this article is included within the Article.

Additional information

Funding

This work was supported by grant from Joint Project of Medical Disciplines of Henan Province [LHGJ20200428, Bijun Wang].