Effect of Ezrin on regulating trophoblast cell invasion via PKC signaling pathway in unexplained recurrent spontaneous abortion.

Trophoblast cells are the most important cells in early pregnancy and their invasion are essential to the establishment and maintenance of pregnancy. Inadequate trophoblast cell invasion has been closely associated with several pregnancy-associated diseases including recurrent spontaneous abortion (RSA). Ezrin is an actin-associated protein, known as a marker for carcinogenesis and metastasis in solid tumors, has been proposed to play a role in the formation of microvilli in the early embryo. To further characterize its function in early pregnancy, we explored the expression of Ezrin in the trophoblast cells in early pregnancy. In this study, compared with normal pregnant women, we demonstrated that the expression of Ezrin and phosphorylated Ezrin decreased in the trophoblast cells in unexplained RSA (URSA) patients, and knockdown of Ezrin expression could suppress the invasiveness of trophoblast cells significantly. Various studies indicated that the phosphorylation of Ezrin on C-terminal threonine residue (T567) is a key event in the regulation of its activity. Our further exploration indicated that Ezrin was activated via PKC pathway. Furthermore, inhibition of the PKC pathway by a specific inhibitor suppressed invasiveness of Bewo cells. On the other hand, activation of the PKC pathway could increase the relative capacity of trophoblast cell invasion, while Ezrin knockdown reversed PKC activation induced cell invasion. These findings might provide a new fundamental mechanism for successful pregnancy and new diagnostic and therapeutic target for RSA.