Mifepristone (RU486) Inducing Abortion in a Mouse Model by Regulating Innate and Adaptive Immune Responses  

作　　者：Meng-Die Li Yi-Fei Sang Yun-Hui Tang Ling Xu Chun-Fang Xu Da-Jin Li Yan-Hong Li Jian-Ping Zhang Mei-Rong Du 

机构地区：[1]Laboratory for Reproductive Immunology,NHC Key Lab of Reproduction Regulation(Shanghai Institute of Planned Parenthood Research),Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases,Hospital of Obstetrics and Gynecology,Fudan University Shanghai Medical College,Shanghai 230032,China [2]Department of Gynecology,Jing’an District Central Hospital,Fudan University,Shanghai 200040,China [3]Laboratory for Reproductive Immunology,Obstetrics and Gynecology Hospital,Fudan University,Shanghai 200032,China

出　　处：《Reproductive and Developmental Medicine》2020年第2期63-71,共9页生殖与发育医学（英文版）

基　　金：supported by the National Key R&D Program of China(Grant nos.2017YFC1001403 to MRD and 2017YFC1001404 to DJL);the Nature Science Foundation from National Nature Science Foundation of China(Grant Nos.31970859,81630036 to MRD,and 31900663 to YHL);the Program of Shanghai Academic/Technology Research Leader(Grant No.17XD 1400900 to MRD);the Innovation oriented Science and Technology Grant from NPFPC Key Laboratory of Reproduction Regulation(Grant No.CX20172 to MRD).

摘　　要：Objective:Mifepristone(RU486),one of the most common medications for artificial abortion,attenuates the immunoregulatory effects of progesterone.However,the specific immune regulatory mechanism of RU486 in abortion remains unknown.We intended to investigate the immunomodulatory effects of RU486 on abortion.Methods:Sixty female mice were divided into the control group(0 mg RU486)and RU486 group(2 mg/kg RU486).The uterus,peripheral blood,and spleen were obtained for isolation of specific cell types.The population and phenotype of immune cells in the decidua,peripheral blood,and spleen were analyzed using flow cytometry.Statistical differences between groups were determined using two-tailed t-test.For all statistical tests,P<0.05 was considered statistically significant.Results:RU486 effectively induced abortion in pregnant mice,with a significantly higher number of decidual macrophages(dMφ)(control group=25.55%±2.467%,RU486 group=19.41%±1.423%;P<0.05),especially the major histocompatibility complex II high subset.No difference in Mφnumber was observed in the spleen or peripheral blood.Moreover,the dMφfrom mice with RU486-induced abortion displayed a remarkable activated phenotype,with increased expressions of inducible nitric oxide synthase,tumor necrosis factor-α,and interleukin(IL)-12 but decreased expressions of arginase-1 and IL-10.We also found elevated levels of decidual CD4+T-cells in the RU486 group that exhibited a higher level of the proinflammatory cytokine interferon-γand a lower level of the anti-inflammatory cytokines,IL-4 and IL-10.Conclusions:We report a new mechanism of RU486-induced abortion via the regulation of innate cell Mφactivation and the adaptive response of CD4+T-cells present in the decidua but not the periphery.

关 键 词：Decidual CD4+T-Cells Decidual Macrophages Induced Abortion RU486 

分 类 号：R714.21[医药卫生—妇产科学]