Effect of CD86 blockage on the expressions of TGF-β1,MMP-9,TIMP-3 and PAI-1 proteins and outcome of pregnancy in murine abortion-prone model

摘要

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 x DBA/2 matings were used as the abortion-prone model and the CBA/J×BALB/c matings used as the normal pregnant model. The study was performed in following three groups: 2 groups of the abortion-prone model, which were experimental group and control experimental group, and 1 group of normal pregnant model, 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 antimouse CD86 mAb in 200μl of PBS at day 4.5 of gestation, and the irrelevant-isotope matched rat IgG2b was administrated in the control experimental group with the same dosage and at same time. For the normal pregnant 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, TIMP3 and PAI-1 were detected by using immunohistochemical methods. It was demonstrated that the embryo resorption rate in the experimental group was significantly reduced in comparison with that in the control experimental group (x2=7.441,P = 0.006), but there was no significant difference with that in normal pregnant group (x2=0.016, P = 0.898) . The expressions of TGF-β1 and PAI-1 in the experimental group were significantly increased in comparison with that in the control experimental group (P=0.010,P=0.003, respectively), with no significant difference from that in the normal pregnant group (P = 0.500) . However, the expression of MMP-9 in the experimental group was significantly reduced in comparison with that in the control experimental group (P = 0.012) with no significant difference from that in the normal pregnant group (P = 0.500) . The expression of TIMP-3 in the experimental group showed no significant difference both with the control experimental group (P = 0. 328) and the normal pregnant group (P = 0.500) . It is concluded that 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 natural abortion-prone model of mice to the level of normal pregnancy.