The increase of Th1 differentiation marker Tbet and the decrease of Th2 differentiation marker Gata3 implicated that the Th1/Th2 ratio is biased to Th1 dominance after immunization of pCR3.1- IGFBP7-t, and also confirmed the expression profile of the Th1 and Th2 cytokines. At D7 we observed that IFNc was elevated, whereas Th2 cytokines IL-4 and IL-10 were decreased in the uterus after the immunization with pCR3.1-IGFBP7-t. IL-10 is not only a typical Th2 cytokine, but also plays an important role in Treg functioning. Moreover, IL-10 also regulates the vascular remodeling and hypertension to maintain pregnancy. IL-10 could rescue intrauterine growth restriction and MK-0683 HDAC inhibitor proteinuria in IL102/2 mice. The uNK-derived IFNc facilitate the gestation spiral aterial modification. However, excessive IFNc is deleterious to pregnancy. IGFBP1 is recognized as a decidualization marker. In our study, IGFBP1 was significantly reduced in mice at D7 after immunization with pCR3.1-IGFBP7-t, as compared with the controls. This result implicates the insufficient formation of decidual cells as a possible factor that contributes to the partial pregnancy failure. However, apoptosis is involved in the establishment of uterine receptivity, and specific uterine cells undergo apoptosis during decidualization. Caspase3, the final effector protein of apoptosis, was downregulated at D7 after immunization with pCR3.1-IGFBP7-t. Bcl-2, which is well known as an apoptosis-inhibiting protein, was also downregulated at D7. The ratio of Bax/Bcl-2 partially contributes to the cell fate in the mitochondrial apoptosis pathway ; however, Bcl-2 also functions as a cell cycle inhibitor. These results implicated an attenuated apoptosis process in the uteri after the immunization with IGFBP7, which may also contribute to insufficient decidualization. Furthermore, a notable decrease of VEGF was also observed in the pregnant mice immunized with pCR3.1-IGFBP7-t at D7. VEGF is essential for angiogenesis through the regulation of endothelial proliferation and migration ; hence, a high expression of VEGF is beneficial for the growth of the embryos and placenta, whereas a low expression may contribute to inadequate embryo implantation or development. According to our previous research, the effect of DNA immunization was released gradually after immunizations. As the immunizations were prior to the mating of mice, the cumulative effect after immunization with pCR3.1-IGFBP7-t may impair the implantation process. We found out that three molecules, IL-10, Bcl-2 and IGFBP1, were downregulated on D5, while the upregulation of IFNc and the downregulation of IL4, Caspase-3 and VEGF were also observed on D7. This gradual impact on the molecules could partially stand for it. However the further mechanism of IGFBP7 on implantation is still worth devoting in. Overall, we observed alterations in the uterine environment after the immunization with pCR3.1-IGFBP7-t, which was generally disadvantageous for pregnancy maintenance. As the establishment of uterine receptivity is a complex process, it remains unclear whether the observed physiological and immu nological changes are directly due to the interference of IGFBP7 or are secondary effects on decidualization induced by the loss of IGFBP7. The inhibitory effects of pCR3.1-IGFBP7-t immunization on pregnancy genes may not be restricted to the uterus despite the fact that we removed the sequence coding for the highly conserved IGFBP domain in the construction of pCR3.