Studies on the localization of adhesive proteins associated with the development of extravillous cytotrophoblast

It is well known that maternal fibrinogen (Fg) and subunit A of factor XIII (XIIIA) are essential for maintaining early pregnancy. We reported that they were essential from 5 weeks' gestation and were present immunohistochemically at the implantation site. Now we studied the precise localization of Fg, fibronectin (Fn), XIIIA, and subunit S of factor XIII (XIIIS) associated with the development of extravillous cytotrophoblast (EV-CTr) in the human implantation tissues and placenta. Cytotrophoblast cells were confirmed by cytokeratin immunolabeling. The results showed that in the region around the early placental bed, Fg and Fn were present at Nitabuch's layer, and XIIIA was present at the extracellular space of EV-CTrs forming the cytotrophoblastic shell adjacent to Nitabuch's layer. In the decidual stroma near Nibabuch's layer, where interstitial EV-CTrs were infiltrating, Fn was present. However, any obvious localization of Fg, XIIIA and XIIIS could not be detected. In the decidual stroma far from Nitabuch's layer, where interstitial EV-CTrs did not infiltrate, numerous XIIIA positive macrophages were detected. However, any obvious localization of Fg, Fn, plasma and platelet XIIIA, and XIIIS could not be detected. Discussion of the results leads to a hypothesis that maternal Fg, maternal XIIIA and Fn present at the site around the cytotrophoblastic shell are associated with the early placental adhesion. Also, Fn is present at the decidual stroma where interstitial EV-CTrs are infiltrating, so it may be oncofetal Fn and associated with trophoblastic outgrowth and migration. XIIIA positive macrophages and the interstitial EV-CTrs cannot be present together at the decidual stroma. However, XIIIA positive macrophages may play a role in assisting the tetomaternal adhesion.