CD200 Mediated Anti-Inflammatory Response and Vascular Barrier Maintenance in the Development of OHSS Upon Electroacupuncture Treatment

Background: Electroacupuncture (EA) reduces the inflammatory response and improves vascular permeability in hyperstimulation syndrome (OHSS) model rats, however, the mechanism still unclear. Methods: OHSS model rats were established and treated with EA, proteomic of ovaries was performed. CD200 was identified and investigated in ovaries of OHSS rat model following EA treatment. The role of CD200 in patient was evaluated in follicular fluid and serum from IVF patients. The in vitro effects of CD200 on inflammation and vascular barrier were examined in KGN and HUVEC cells. Findings: CD200 was significantly highly expressed, meanwhile, the inflammatory pathway was decreased and the vascular barrier function was improved in EA treated rats. The levels of CD200 in follicular fluid were negatively correlated with the number of oocytes retrieved and serum E2 level. In vitro, the inflammatory response in KGN cells was induced by hCG in a concentration-dependent manner, and inhibited when treated with CD200Fc (CD200R agonist). In HUVECs, the vascular barrier was improved when CM (cultural medium from KGN cell) treated with CD200Fc. Interpretations: Our findings showed the role of CD200 in the development of OHSS upon EA treatment. Meanwhile, CD200 might act as a key molecular maker in predicting the occurrence of OHSS in IVF patients. Funding Statement: This work was supported by the National Key Research and Development Program (Grant No.2018YFC1003800), the National Natural Science Foundation of China (No.81973965 and No.81904043), the Jiangsu Key Research and Development Program (Grant No.BE2018714), the Jiangsu Natural Science Foundation (Grant No.BK20191230 and No.BK20190249), China's Post-doctoral Science Foundation (Grant No.2018M643887), Special Research on Military Family Planning (Grant No.18JS004) and State Key Laboratory of Reproductive Medicine of Nanjing Medical University (Grant No.SKLRM-K201803). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: Samples were collected after obtaining the written informed consent from the patients and ethics board approval from the Nanjing Jinling Hospital (reference number 2018NZGKJ-011). All animal studies (including the rat euthanasia procedure) were done in compliance with the regulations and guidelines of Nanjing Jinling Hospital and were conducted according to the AAALAC and the IACUC guidelines (reference number 20140729).