Blastocyst-mediated induction of endometrial connexins: an inflammatory response?

As a prerequisite for successful embryo implantation in mammals, before implantation ovarian hormones regulate the transformation of the endometrium into the receptive phase. During the implantation process, gene expression in the receptive endometrium is additionally modulated by the presence of a blastocyst. During this complex differentiation process, in humans as well as in rodents, gap junction connexin 26 (Cx26) is suppressed in the uterine epithelium and Cx43 is suppressed in the endometrial stromal cells during the receptive phase. In rodents, a blastocyst-mediated induction of Cx26 takes place locally in the uterine epithelial cells of the implantation chamber surrounding the blastocyst, followed by an increase in Cx43 in the cells of the developing decidua. The Cx26 induction is dependent on the presence of a blastocyst and occurs even before adhesion and invasion of the trophoblast takes place. The signal cascades involved in this blastocyst-mediated connexin induction are still elusive. The process of implantation is considered as a proinflammatory response, and inflammatory factors have been shown to be involved in the implantation process. In fact, Cx26 expression can be induced in the receptive rat endometrium by mediators of the inflammatory cascade including prostaglandin-F2α and IL1β by an ER-independent pathway similar to the blastocyst-mediated connexin induction at the time of implantation. Thus, in the receptive endometrium induction of connexin expression may also be induced by mediators of the inflammatory signaling cascade, and the implantation-related induction of intercellular communication may in part be due to an inflammatory response.