OP005. Preeclampsia is associated with the presence of transcriptionally active placental fragments in the maternal lung.

INTRODUCTION Preeclampsia is associated with increased levels of the circulating anti-angiogenic factor sFlt-1 as well as with an excessive shedding of placenta-derived multinucleated syncytial aggregates into the maternal circulation. However, it remains unclear whether these aggregates are transcriptionally active in the maternal organs and can therefore contribute to the systemic manifestations of preeclampsia. OBJECTIVES We hypothesized that in preeclampsia, syncytial knots are the primary placental site of sFlt-1 production and that increased numbers of sFlt-1-containing syncytial aggregates are retained in the maternal lungs. METHODS In this study, we measured placental sFlt-1 mRNA levels in preeclamptic- and control placentas and performed RNA in situ hybridization to localize the main placental expression site of sFlt-1 mRNA. Because the maternal lung is the first capillary bed that circulating syncytial aggregates traverse, we studied the presence and persistence of placental material in lungs of preeclamptic women and control subjects. To confirm the placental origin of suspected syncytial aggregates in these lungs, immunohistochemistry for the placenta-specific marker hCG and Y-chromosome in situ hybridization were performed. RESULTS Using human placental tissue, we found that syncytial knots are the principal site of expression of the anti-angiogenic factor sFlt-1. In addition, in autopsy material obtained from women with preeclampsia (n=9), we observed significantly more placenta-derived syncytial aggregates in the lungs than in control subjects (n=26). Importantly, these placental aggregates still contained the anti-angiogenic factor sFlt-1 following their entrapment in the maternal lungs. CONCLUSION The current study confirms the important role of syncytial knots in placental sFlt-1 mRNA production. Additionally, it shows a significant association between preeclampsia and larger quantities of sFlt-1 containing syncytial aggregates in maternal lungs, suggesting that the transfer of syncytial aggregates to the maternal compartment may contribute to the systemic endothelial dysfunction that characterizes preeclampsia.