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.

中文翻译：

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亲环蛋白 A 通过激活 Stat3 在胚胎植入中起重要作用

胚胎植入是成功建立哺乳动物妊娠的关键步骤。亲环蛋白 A (CyPA) 是一种普遍表达的细胞内蛋白，分泌以响应炎症刺激以调节多种细胞功能。然而，目前还没有关于 CyPA 在胚胎植入中的作用的报道。在这里，我们检查了小鼠早期妊娠期间 CyPA 的表达模式，并探讨了 CyPA 在植入过程中的潜在作用。CyPA 在怀孕第 5 天在植入囊胚周围的腔下基质中表达，但不在植入间位点表达。在切除卵巢的小鼠中，雌激素和孕激素显着刺激 CyPA 表达。当怀孕小鼠腹腔注射 CyPA 抑制剂时，植入部位的数量显着减少。使用体外基质细胞培养系统，Ppia siRNA 敲低 CyPA 和 CyPA 特异性抑制剂治疗部分抑制 CD147、MMP3 和 MMP9 的水平。降低的 CyPA 表达也显着抑制 Stat3 活性并扩大雌激素反应性。总之，CyPA 可能在小鼠胚胎植入过程中发挥重要作用。