Crosstalk between human endometrial stromal cells and decidual NK cells promotes decidualization in vitro by upregulating IL-25

Embryo implantation is essential for a successful pregnancy, and leads to the decidualization of endometrial stromal cells (ESCs) in the secretory phase of the menstrual cycle. It has previously been demonstrated that decidual stromal cells (DSCs) co-express interleukin (IL)-25/IL-17RB and that IL-25 further promotes the proliferation of DSCs via activating c-Jun n-terminal kinase and protein kinase B signals, therefore the present study primarily focused on the role of IL-25 in the process of decidualization in vitro. It was demonstrated that the expression of IL-25/IL-17RB in ESCs was decreased compared with DSCs. In addition, following decidualization, the expression levels of IL-25/IL-17RB in ESCs were significantly elevated. Recombinant human (rh) IL-25 promoted the decidualization of ESCs in the presence of 8-bromoadenosine 3′,5′-cyclic monophosphate sodium salt and 6α-methyl17α-acetoxyprogesterone, which was partially inhibited by anti-human IL-25 neutralizing antibody (anti-IL-25) or anti-IL-17RB. In addition, decidual natural killer (dNK) cells not only secreted IL-25, however also further accelerated the decidualization in vitro. Therefore, these findings indicated that ESCs differentiate into DSCs in the presence of ovarian hormones, resulting in the upregulation of IL-25/IL-17RB expression in ESCs. Furthermore, IL-25 secreted by ESCs and dNK cells further facilitates the decidualization of ESCs, which may form a positive feedback mechanism at the maternal-fetal interface and thus contribute to the establishment and maintenance of normal pregnancy.