Restricting factor for a successful pregnancy, is a cross-talking process that consists of trophoblast invasion into the maternal endometrium and the formation of maternal uterine receptivity. Approximately 75% of pregnancy failures are due to abPLX4032 Raf inhibitor normal embryo implantation and placenta formation. Our previous research has elucidated that IGFBP7 regulates the human trophoblast proliferation and invasion. Multiple biological processes are of key importance for embryo implantation. Decidual cells are differentiated from ESCs with the secretion of IGFBP1, and they perform functions in producing growth factors and cytokines, regulating maternal immune responses and restricting trophoblast invasion. Furthermore, embryo implantation relies on extensive vascular remodeling in the endometrial stroma to provide enough nutrients and oxygen for the growing embryos, and uterine decidualization and angiogenesis are crucial for the establishment and maintenance of uterine receptivity. In this study, the expression and function of IGFBP7 in uterus was studied by a specific DNA immunization containing truncated IGFBP7 cDNA in mice. The post-implantation pregnancy failure was significantly higher in the mice immunized with IGFBP7-t expressing plasmid, pCR3.1-IGFBP7-t. We also found that a shift of the cytokine balance to Th1 type dominance and defective stromal decidualization were involved in the pregnancy failure induced by inhibition of IGFBP7. Successful pregnancy in primates requires a well-established decidua and an adaptable immune microenvironment. In the mouse, embryos implant into the uterus at D4.5 in a normal pregnancy. A series of cell transformation and differentiation events then takes place, and immediately after implantation, ESCs transform into decidual cells to establish uterine receptivity. In vitro studies have shown that IGFBP7 is expressed and secreted in ESCs, and the inhibition of IGFBP7 in ESCs induces the decrease of IGFBP1 and prolactin. However, the role of IGFBP7 in vivo has yet to be clearly elucidated. In this study, we constructed a vector, pCR3.1-IGFBP7-t, containing a truncated IGFBP7 coding sequence in order to investigate the effect of IGFBP7 on uterine receptivity and pregnancy in female mice. The immunizations were based on our previous reports and involved preinoculation with the muscle-damaging agent bupivacaine at the injection sites one day before the DNA immunization. Our in vitro validation of the expression and specificity showed the successful expression of pCR3.1-IGFBP7-t mRNA, and the antibody generated by the immunization with pCR3.1-IGFBP7-t specifically reacted with the IGFBP7-t expressed by pCR3.1-IGFBP7-t in transfected Hela cells. Both the pregnancy rate and number of implanted embryos were significantly reduced after the immunization with pCR3.1-IGFBP7-t. The immune microenvironment of the uterus is crucial for the maintenance of pregnancy, and cytokines are considered to be key regulators. Previously pregnancy was recognized as a predominant Th2 immunity event, which may protect the fetus from being attacked by Th1 cells. However, predominant Th2 type immunity was found in abortion cases, and the typical Th2 type cytokines IL-4 and IL-10 KO mice are fertile. These evidences indicate that Th2 dominance is insufficient in pregnancy. Now the Th1/Th2 paradigm has been expanded into Th1/Th2/Th17 and regulatory T cells paradigm. Th17 cells play a role in inflammation, while Treg cells are important in immunoregulation and immunotolerance. The differentiation of both Th17 and Treg cells from naive T cells require the involvement of TGFb.