Symposium 2-1 - Role of exosomes in placenta-maternal body axis for organ specific damage of preeclampsia

Abstract

Exosomes are extra-cellular vesicles that are released from many cells, which are taken up by distant organs and alter those cell phenotype. Preeclampsia (PE) is characterized by hypertension and diverse organ damage. However, the underlying causes of specific maternal organ damage remain largely unexplained. We focused on exosomes released by placenta and aimed to investigate whether they have a role in maternal organ damage in PE. We obtained exosomes from placentas of pregnant women with and without PE who gave birth at the University of Tokyo Hospital. Isolated exosomes were administered to pregnant mice from E11.5 to examine their effects on the mother and fetuses. A significant increase in proteinuria was observed in pregnant mice treated with exosomes derived from placenta of PE patients (PE group) compared to those of normal pregnancies (normal group). Whereas, blood pressure and the fetus size and numbers were not affected. This phenomenon was due to the selective uptake of PE exosomes in kidney, which was mediated by surface molecules on the exosomes. Gene expression analysis of kidney in PE group showed pathway changes associated with potential damage in kidney function. Moreover, pathological analysis revealed glomerular endotheliosis, which is a characteristic of PE. In other organs, pathological changes that could be related to the pathogenesis of PE were observed in the brain and liver in the PE group. Our results indicate the existence of an exosome-mediated organ-specific connection between placenta and maternal organs, which may explain organ-selective damages in PE patients.