PAI‐1 promotes human endometrial stromal decidualization via inhibiting VEGFR2/PI3K/AKT signaling pathway mediated F‐actin reorganization

Abstract Decidualization of endometrial stromal cells is a prerequisite for successful embryo implantation and early pregnancy. Decidualization dysregulation results in implantation failure. In our previous study, we reported that PAI‐1 is abnormally downregulated in the endometrial tissue samples of patients with recurrent implantation failure. This study will explore the dynamic expression changes of PAI‐1 in the endometrium during the menstrual cycle and its molecular mechanism affecting endometrial decidualization. Our findings indicated that the abundance of PAI‐1 increased in the mid‐secretory phase and attached a peak in the decidual phase in the endometrium of women with regular menstrual cycles. In human endometrial stromal cells (HESCs), PAI‐1 knockdown attenuated endometrial decidualization by upregulating VEGFR2/PI3K/AKT signaling pathway and impaired the F‐actin reorganization. Furthermore, axitinib (a VEGFR2 inhibitor) was used to inhibit the VEGFR2 protein activity and the results suggested that it eliminated the effects of PAI‐1 on PI3K/AKT signaling pathways and F‐actin remodeling. In addition, the interaction between PAI‐1 and KNG1 was confirmed by coimmunoprecipitation assay in HESCs. Altogether, PAI‐1‐KNG1 may enhance the decidualization of endometrium by inhibiting VEGFR2/PI3K/AKT signaling pathway‐mediated F‐actin reorganization in healthy females.