Cyclophilin A plays an important role in embryo implantation through activating Stat3.

Embryo implantation is a crucial step for the successful establishment of mammalian pregnancy. Cyclophilin A (CyPA) is a ubiquitously expressed intracellular protein and is secreted in response to inflammatory stimuli to regulate diverse cellular functions. However, there are currently no reports about the role of CyPA in embryo implantation. Here, we examine the expression pattern of CyPA during mouse early pregnancy and explore the potential role of CyPA during implantation. CyPA is expressed in the subluminal stroma surrounding the implanting blastocyst on day 5 of pregnancy, but not at inter-implantation sites. In ovariectomized mice, estrogen and progesterone significantly stimulate CyPA expression. When pregnant mice are injected intraperitoneally with CyPA inhibitor, the numbers of implantation sites are significantly reduced. Using an in vitro stromal cell culture system, Ppia siRNA knock-down of CyPA and CyPA specific inhibitor treatment partially inhibits levels of CD147, MMP3 and MMP9. Decreased CyPA expression also significantly inhibits Stat3 activity and expands estrogen responsiveness. Taken together, CyPA may play an important role during mouse embryo implantation.