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

Li Chen,Xie Ge,Minghui Gu,Li Wang,Xuan Huang,Cencen Wang,Jun Jing,Rujun Ma,Xu Tang,Bing Yao

doi:10.3389/fcell.2021.648578

Abstract

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.

Highlights

Ovarian hyperstimulation syndrome (OHSS) is a common complication caused by ovulatory stimulation therapy
The rats in the control group received 10 IU pregnant mare serum gonadotropin (PMSG) (Ningbo, China) on D27, followed by injection of 10 IU human chorionic gonadotropin (hCG) (Ningbo, China) on D29 to induce ovulation; the OHSS rats were administered with PMSG (50 IU/day) for 4 days from D25 to D28 followed by injection of 150 IU hCG on D29; the EA + OHSS (EAO) rats underwent the same hormonal stimulation protocol as OHSS group in addition to EA stimulation for 15 min/day from D22 to D31
The EAO group showed a distinct gene expression pattern when compared with the OHSS group, suggesting a significant impact of EA treatment on protein expression

Summary

Introduction

Ovarian hyperstimulation syndrome (OHSS) is a common complication caused by ovulatory stimulation therapy. It is characterized by enlarged ovary, higher number of oocytes, and increased vascular permeability, resulting in redistribution of intravascular fluid to the third space of the body and leading to clinical syndrome which includes ascites, pleural effusion, and oliguria (Veisi et al, 2013; Kwik and Maxwell, 2016). OHSS is attributable to the massive increase in systemic inflammatory cytokines and vasoactive factors present in the serum, follicular, and ascetic fluid, including vascular endothelial growth factor (VEGF), interlukin-1β, IL-6, TNFα, and so on (Loret de Mola et al, 1996, 1997; Pellicer et al, 1999; Artini et al, 2002; Orvieto, 2004). There are no universal guidelines or strategies for OHSS management due to controversies in treatment options

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