Electroacupuncture Reduces Oocyte Number and Maintains Vascular Barrier Against Ovarian Hyperstimulation Syndrome by Regulating CD200.

Electroacupuncture Reduces Oocyte Number and Maintains Vascular Barrier Against Ovarian Hyperstimulation Syndrome by Regulating CD200.
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电针通过调节 CD200 减少卵母细胞数量并维持血管屏障,对抗卵巢过度刺激综合征

DOI:
10.3389/fcell.2021.648578
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发表时间:
2021
影响因子:
5.5
通讯作者:
Yao B
Yao B
中科院分区:
生物学2区
文献类型:
--
作者:
Chen L;Huang X;Wang L;Wang C;Tang X;Gu M;Jing J;Ma R;Ge X;Yao B

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卵巢过度刺激综合征(OHSS)是由促排卵治疗引起的常见并发症,其表现为卵巢体积增加,获卵数增加,全身尤其是卵巢组织的血管通透性增加。我们在前期研究中发现,电针主要通过作用于卵巢而起到预防OHSS进展的作用。然而,这一过程的具体分子和机制仍然未知。为探讨其作用机制,建立OHSS大鼠模型,采用电针治疗,并对卵巢进行蛋白质组学分析。结果显示,电针治疗组卵巢组织中CD 200的表达水平明显高于OHSS组。临床资料显示,卵泡液中CD 200水平与获卵数和血清E2水平呈负相关。进一步的体外实验显示,人绒毛膜促性腺激素(hCG)在降低培养的KGN细胞中的CD200和CD200 R水平以及增加炎性细胞因子水平方面具有浓度依赖性作用。在人脐静脉内皮细胞(HUVECs)中,用CD200Fc(CD200R激动剂)处理的CM(来自KGN细胞的培养液)改善血管屏障功能。同时,体内实验结果表明,电针可减少大鼠卵巢黄体数量,减轻炎症反应,并通过增加卵巢CD200和CD200R的表达,改善血管屏障功能。这些结果表明,EA治疗可能通过CD200介导的卵巢抗炎反应减少卵母细胞数量,并维持血管屏障对抗OHSS。因此,本研究首次明确了CD200在电针治疗卵巢过度刺激综合征中的作用,阐明了电针防治OHSS的可能机制,为CD200作为电针治疗OHSS的效应物和指标提供了科学依据。
Ovarian hyperstimulation syndrome (OHSS) is a common complication caused by ovulatory stimulation therapy, which manifests as an increase in ovarian volume, an increase in the number of oocytes retrieved, and increased vascular permeability throughout the body and especially in ovarian tissue. In our previous study, we found that electroacupuncture (EA) could prevent the progression of OHSS, by mainly affecting ovary. However, the specific molecules and the mechanism of this process were still unknown. In order to explore the underlying mechanism, OHSS rat model was established and EA treatment was performed, which was followed by proteomic analysis of ovaries. Results showed a significant increase in the expression level of CD200 in the ovaries of OHSS group treated with EA than those of OHSS group. Clinical data showed that the level of CD200 in follicular fluid was negatively correlated with the number of oocytes retrieved and serum E2 level. Further in vitro experiments showed a concentration-dependent role of human chorionic gonadotropin (hCG) in reducing CD200 and CD200R levels, and increasing inflammatory cytokine levels in cultured KGN cells. In human umbilical vein endothelial cells (HUVECs), the vascular barrier function was improved by CM (cultural medium from KGN cell) which treated with CD200Fc (CD200R agonist). Meanwhile, the results of in vivo experiments indicated that EA reduced the number of ovarian corpora lutea, decreased inflammatory response, and improved the vascular barrier function by increasing the expression of CD200 and CD200R in rat ovaries. These findings suggest that EA treatment may reduce oocyte number and maintain vascular barrier against OHSS through ovarian anti-inflammatory response mediated by CD200. Therefore, this study is the first to identify CD200 as a main of EA in the ovary and elucidate the possible mechanism of EA on preventing and treating OHSS, which provide a scientific basis for CD200 as an effector and indicator in EA treatment.
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