COMMON MECHANISMS GOVERN THE EXPRESSION OF P21RAS AND CLASS-II MHC ANTIGENS IN THE MURINE PLACENTA

It has been shown that there is an inverse as well as a direct correlation between class II MHC antigen expression and the p21ras protein, depending on the cell type. By using trophoblastic cells derived from the spongiotrophoblast and labyrinthine trophoblast, the two major components of the murine placenta, we have examined the p21ras. expression in these populations and how this correlates with the induction of class II MHC antigens. It has been shown that although only a small number of cells express the p21ras and class II proteins, they can be induced to express higher levels of these markers by two different treatments. Thus, gamma-interferon (gamma-IFN) induces p21ras and class II protein expression in spongiotrophoblast-derived cells, whereas 5-Azacytidine (5-AzaC) induces expression of these antigens in labyrinthine trophoblast-derived populations. Furthermore, it has been demonstrated that there is a direct correlation between the two markers, as blocking antibody to p21ras cancels the ability of gamma-IFN and 5-AzaC to induce class II antigens. As previous work from this laboratory has shown that in vivo class II induction in the placenta leads to fetal abortion, the present results suggest that both proteins are involved in a common signal transduction pathway which may lead to disruption of fetal membranes and fetal loss.