Higher melatonin in the follicle fluid and MT2 expression in the granulosa cells contribute to the OHSS occurrence
Higher melatonin in the follicle fluid and MT2 expression in the granulosa cells contribute to the OHSS occurrence
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卵泡液中较高的褪黑激素和颗粒细胞中较高的 MT2 表达有助于 OHSS 的发生
DOI：
10.1186/s12958-019-0479-6
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发表时间：
2019-04-12
影响因子：
4.4
通讯作者：
Sun, Yingpu
中科院分区：
文献类型：
--
作者：
Li, Yiran;Fang, Lanlan;Sun, Yingpu
背景：卵巢过度刺激综合征（OHSS）是IVF/ICSI-ET患者常见且严重的并发症。褪黑素广泛参与调节女性生殖内分泌活动。然而，褪黑素是否参与OHSS的进展在很大程度上是未知的。本研究旨在确定卵泡液褪黑素对OHSS建立的预测价值及其潜在机制。方法：本病例对照研究的所有参与者均于2017年1 - 10月在中国郑州大学第一附属医院生殖医学中心入选。采用实时荧光定量PCR和western blot检测mRNA和蛋白水平。提取原代颗粒细胞进行体外培养。ELISA法测定褪黑素浓度。采用Logistic分析和受试者工作特征（ROC）曲线评价褪黑素对OHSS发生的预测价值。主要观察指标：褪黑激素受体2 （MT2）、P450芳香化酶细胞色素（芳香化酶）、血管内皮生长因子（VEGF）、诱导型一氧化氮合酶（iNOS） mRNA在人原代颗粒细胞中的表达水平。FF中褪黑激素的浓度。褪黑素对OHSS的预测值及预测值的临界值。结果：OHSS患者FF褪黑素浓度显著高于非OHSS组（35.94 +/- 10.18 ng/mL vs 23.93 +/- 10.94 ng/mL, p < 0.001）。OHSS组颗粒细胞中MT2 mRNA和蛋白的表达也显著升高（p = 0.0459）。当临界值为27.52 ng/ml时，FF褪黑素预测OHSS的敏感性和特异性分别为84.6%和74.0% （p < 0.0001）。我们还发现褪黑素可以上调颗粒细胞中芳香化酶mRNA、VEGF mRNA的表达，下调iNOS mRNA的表达。结论：OHSS患者FF中褪黑素升高，颗粒细胞中MT2表达升高。FF中褪黑素可作为OHSS发生的有效预测因子。
Background: Ovarian hyperstimulation syndrome (OHSS) is a common and severe complication for patients undergoing IVF/ICSI-ET. Melatonin widely participates in the regulation of female reproductive endocrine activity. However, whether melatonin participates in the progression of OHSS is largely unknown. This study aims to identify the predictive value of follicular fluid (FF) melatonin for OHSS establishment and the underlying mechanism.Methods: All participants of this case-control study were enrolled at the Reproductive Medicine Center located in the First Affiliated Hospital of Zhengzhou University in China from January to October in 2017. Quantitative real-time PCR and western blot were used to examine the mRNA and protein levels. Primary granulosa cells were extracted and cultured for in vitro studies. Melatonin concentration was measured by ELISA. Logistic analysis and receiver-operating characteristic (ROC) curves were used to evaluate the predicting value of melatonin on OHSS occurrence.Main outcome measures: The expression level of melatonin receptor 2 (MT2), P450 aromatase cytochrome (aromatase), vascular endothelial growth factor (VEGF), and inducible nitric oxide synthase (iNOS) mRNA in human primary granulosa cells. The concentration of melatonin in FF. The predicting value of melatonin on OHSS and the cut-off value of the prediction.Results: FF melatonin concentrations were significantly higher in patients with OHSS compared to non-OHSS group (35.94 +/- 10.18 ng/mL vs 23.93 +/- 10.94 ng/mL, p < 0.001). The expression of MT2 mRNA (p = 0.0459) and protein in granulosa cells was also significantly higher in the OHSS group. When using a cut-off level of 27.52 ng/ml, the sensitivity and specificity of FF melatonin to predict OHSS was 84.6 and 74.0%, respectively (p < 0.0001). We also found that melatonin could up-regulates aromatase mRNA, VEGF mRNA expression and down-regulates iNOS mRNA expression in the granulosa cells.Conclusion: OHSS patients have higher melatonin in the FF as well as higher MT2 expression in the granulosa cells. The melatonin in FF might be used as an effective predictor for the occurrence of OHSS.