Abstract

Appropriate decidualization is of great importance for embryo implantation , placental development and successful pregnancy. Although it has been well-acknowledged that decidualization relies on activation of progesterone-mediated signaling pathway , the exact mechanisms have not been elucidated. Here, we demonstrated that both IL-27 and IL27RA were highly expressed in decidua than those in endometrium during secretory phase. Estrogen plus progesterone significantly upregulated the expression of IL-27 and IL-27RA in endometrium stromal cells (ESCs). In addition, inhibiting IL-27 signaling with IL-27 neutralization antibody (anti-IL-27) suppressed the expression of decidualization-related molecules, receptors of estrogen (gene coded by ESR ) and progesterone ( PGR ) induced by cAMP or estrogen plus progesterone. Similar results were obtained from Il27ra -/- (knockout of Il27ra ) female mice. Moreover, knockout of Il27ra did not affect the estrus cycle and folliculogenesis in mice but reduced implantation rate with the impairing decidualization. Mechanistically, IL-27 upregulated the expression of ESR1, ESR2 and PGR in ESCs and DSCs, as well as the phosphorylation level of STAT3 . In the presence of estrogen plus progesterone, treatment with ESCs with anti-IL-27 inhibited the activation of STAT3. Also, the expression of ESR, PGR was decreased in Il27ra -/- mice. In conclusion, these findings demonstrate that IL-27 upregulated by estrogen and progestogen promotes decidualization possibly through a STAT3-dominant pathway.