Effect Of Blockage Of Costimulatory Signal CD86 On Murine Abortion-prone Model

Objective In the present study,the effect of blockage of the costimulatory signal CD86 at time of implantation on the expressions of TGF-β1,MMP-9,TIMP-3 and PAI-1 proteins at the maternal-fetal interface and the outcome of pregnancy in murine abortion-prone model was investigated,in which the CBA/J×DBA/2 matings were used as the abortion-prone model and the CBA/J×BALB/c matings used as the normal pregnant model.Methods The study was performed in following three groups:2 groups of the abortion-prone model,which were experimental group and control group,and 1 group of normal pregnant model,which was normal group,and each group had 10 pregnant CBA/J mice exclusively. Female pregnant CBA/J mice in the experimental group received an intraperitoneal(i.p) injection of 100μg of anti-mouse CD86 mAb in 200μl of PBS at day 4.5 of gestation,and the irrelevant-isotope matched rat IgG2b was administrated in the control group with the same dosage and at the same time.For the normal group,no treatment was given.The pregnant CBA/J mice were killed on day 13.5 of gestation.Then,the embryo resorption rate was calculated and the expressions of TGF-β1,MMP-9,TIMP-3 and PAI-1 were detected by using immunohistochemical methods.Results The embryo resorption rate in the experimental group was significantly reduced in comparison with that in the control group(P<0.05),but there was no significant difference with that in normal group(P>0.05).The expressions of TGF-β1 and PAI-1 in the experimental group were significantly increased in comparison with that in the control group(P<0.05),with no significant difference from that in the normal group(P>0.05).However,the expression of MMP-9 in the experimental group was significantly reduced in comparison with that in the control group(P<0.05)with no significant difference from that in the normal group(P>0.05). The expression of TIMP-3 in the experimental group showed no significant difference both with the control group and the normal group(P>0.05).Conclusions The blockage of the costimulatory molecule CD86 at early stage of gestation can render TGF-β1,MMP-9,TIMP-3 and PAI-1 proteins to express their immuno-tolerant effects through their characteristic pathways and induce the reduction of the embryo resorption rate in the murine abortion-prone model to the level of normal pregnancy.