Melatonin Ameliorates Ovarian Hyperstimulation Syndrome (OHSS) through SESN2 Regulated Antiapoptosis.

IF 1.6 Q3 OBSTETRICS & GYNECOLOGY Obstetrics and Gynecology International Pub Date : 2023-10-28 eCollection Date: 2023-01-01 DOI:10.1155/2023/1121227
Min Zheng, Mei Liu, Cong Zhang
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Abstract

Background: Ovarian hyperstimulation syndrome (OHSS) is one of the most severe complications after ovarian stimulation during assisted reproductive technology (ART). However, its pathogenesis still remains unclear. Melatonin is an important antioxidant factor in female reproduction and Sestrin-2 (SESN2) is reported to be involved in cellular response to different stress conditions. Whether or not melatonin and SESN2 are involved in OHSS is still a question to us clinicians.

Methods and results: We collected the granulosa cells of OHSS patients and focused on the role of SESN2 in OHSS. We also studied the role and mechanism of melatonin plays in OHSS patients. We found that the expression of SESN2 was increased in the granulosa cells of OHSS patients (n = 24) than those in controls (n = 15). Incubation with angiotensin II (1 μM, 2 μM) in HUVECs and H2O2 (0.1 mM, 0.2 mM) in KGNs increased the generation of ROS concurrent with the increased expression of SESN2, while melatonin treatment partly restored SESN2 levels. The mechanism study demonstrated that SESN2 was deeply involved in the regulation of AMPK and mTOR, whereas melatonin partially restored angiotensin II or H2O2 induced the activation of AMPK phosphorylation and the inhibition of mTOR, 4EBP1 and S6K1 phosphorylation, all of which could trigger cell apoptosis.

Conclusions: These findings indicated that melatonin attenuated ROS-induced apoptosis through SESN2-AMPK-mTOR in OHSS. Thus, melatonin is likely to be a potential and important therapeutic agent for treating and preventing OHSS.

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褪黑素通过SESN2调节的抗细胞凋亡改善卵巢过度刺激综合征(OHSS)。
背景:卵巢过度刺激综合征(OHSS)是辅助生殖技术(ART)中卵巢刺激后最严重的并发症之一。然而,其发病机制仍不清楚。褪黑激素是女性生殖中的一种重要抗氧化因子,据报道Sestrin-2(SESN2)参与了细胞对不同应激条件的反应。褪黑素和SESN2是否参与OHSS仍然是我们临床医生的一个问题。方法和结果:我们收集了OHSS患者的颗粒细胞,并重点研究SESN2在OHSS中的作用。我们还研究了褪黑激素在OHSS患者中的作用及其机制。我们发现SESN2在OHSS患者颗粒细胞中的表达增加(n = 24)比对照组(n = 15) 。与血管紧张素II(1 μM,2 μM)和H2O2(0.1 mM,0.2 mM)增加ROS的产生同时增加SESN2的表达,而褪黑素处理部分恢复SESN2水平。机制研究表明,SESN2深度参与AMPK和mTOR的调节,而褪黑素部分恢复血管紧张素II或H2O2诱导AMPK磷酸化的激活和mTOR、4EBP1和S6K1磷酸化的抑制,所有这些都可以触发细胞凋亡。结论:这些发现表明褪黑素通过SESN2 AMPK mTOR在OHSS中减弱ROS诱导的细胞凋亡。因此,褪黑素可能是治疗和预防OHSS的一种潜在而重要的治疗剂。
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来源期刊
Obstetrics and Gynecology International
Obstetrics and Gynecology International OBSTETRICS & GYNECOLOGY-
CiteScore
3.60
自引率
0.00%
发文量
26
审稿时长
19 weeks
期刊介绍: Obstetrics and Gynecology International is a peer-reviewed, Open Access journal that aims to provide a forum for scientists and clinical professionals working in obstetrics and gynecology. The journal publishes original research articles, review articles, and clinical studies related to obstetrics, maternal-fetal medicine, general gynecology, gynecologic oncology, uro-gynecology, reproductive medicine and infertility, reproductive endocrinology, and sexual medicine.
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