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.
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).
