Preeclampsia is one of the leading causes for maternal and fetal mortality and morbidity. Placental protein 13 (PP13), a placenta specific protein exclusively expressed in the placental syncytiotrophoblast, is one of the most promising markers to predict the syndrome in early pregnancy, since decreased maternal serum levels occur in the first trimester of affected pregnancies compared to healthy controls. In clinical trials attempts to prevent preeclampsia have already been made using low-dose aspirin, low-molecular-weight heparin, and antioxidants such as vitamins C and E. In this study BeWo cells were selected amongst five different trophoblast derived cell lines used as surrogates for primary villous trophoblast to assess the effect of varying concentrations of vitamin C, acetylsalicylic acid (ASA), Trolox and heparin on cell fusion and protein expression of PP13 and beta-hCG. The response to vitamin C showed a dose dependent increase of the expression of both proteins, while the other drugs showed only modest effects. Since first trimester PP13 has been shown to be significantly decreased in women subsequently developing preeclampsia, this data might point to a beneficial effect of very early vitamin C treatment of such women already in the early first trimester of pregnancy. Furthermore the use of beta-hCG as a marker for syncytialisation was challenged by inhibiting the forskolin induced pathway of cell fusion. In the presence of the protein kinase A inhibitor H-89, cell fusion and PP13 expression were blocked. Even though fusion events decreased dramatically, beta-hCG protein expression remained unaffected. This leads to the assumption that beta-hCG is not necessarily linked to cell fusion and should therefore no longer be used as a marker for syncytialisation.
REGULATION OF PP13 AND BETA-HCG EXPRESSION IN THE CONTEXT OF THERAPEUTIC INTERVENTION OF PREECLAMPSIA IN BEWO CELLS
Aubell, K. (Author). 2010
Student thesis: Doctoral thesis