*2.7. Interleukin-1b in Blastocyst–Endometrium Dialogue*

Interleukin (IL)-1β is another important factor supporting blastocyst–endometrium dialogue, playing a fundamental role in decidualization of stromal cells and in successful blastocyst implantation. IL-1β is secreted by cytotrophoblast cells isolated from first trimester placenta, while its expression is lower in cultures from second and third trimester placenta [184]. In endometrial stromal cells IL-1β induces the expression of COX2 and PGE2, known to increase the levels of cAMP, which are necessary

for decidualization, as above described [185,186]. Moreover, in vivo infusion of IL-1β and CG promotes the expression of IGFBP1 in apical surface stromal cells [133]. It has been demonstrated that inhibition of COX2 in human and baboon endometrial stromal cells is able to block the decidualization induced by IL-1β in the presence of steroid hormones, suggesting that IL-1β acts upstream of COX2 [185]. On the contrary, inhibition of COX2 does not affect decidualization induced by cAMP and steroid hormones, suggesting that cAMP acts downstream of COX2 and PGE2 [185]. Interestingly, cAMP is able to block decidualization induced by IL-1β indicating a negative feedback between IL-1β and cAMP [185,187]. In baboon, IL-1β positively regulates the expression of matrix metalloproteinase (MMP) 3 in endometrial stroma, thus inducing degradation of the ECM. Considering that disruption of the ECM might reflect in cellular cytoskeleton remodeling, IL-1β may play an important role in the decidualization also by promoting cytoskeleton changes typical of this process [188,189]. All these data clearly indicate that IL-1β plays a relevant role in blastocyst–endometrium crosstalk.
