321: Maternal preeclampsia epigenetically alters differentiation potential of endothelial progenitor cells in offspring

Abstract

Recent evidence suggests that offspring delivered from preeclamptic women remains increased risk for long-term, adulthood issues such as cardiovascular and metabolic diseases which may be contributed to in utero environment causing fetal cell programming. Decreased number of fetal circulating endothelial progenitor cells (EPC) in preeclampsia is known, however, their functionality have not been described in detail. We aim to investigate functional impairment and possible epigenetic change of EPCs in offspring born to preeclamptic mother. Human umbilical cord blood EPCs were purified using a magnetic cell sorter device in severe preeclampsia (n=10) and gestationally matched normal pregnant women (n=10). Differentiation of EPCs to outgrowth endothelial cells (OECs) was assessed by morphology, differentiation day and the number of colonies using light microscopy in both groups. Angiogenic function of OECs differentiated from EPCs was evaluated by migration, adhesion and tube formation assay. To identify the change of differentiation potency of EPCs and angiogenic function of OECs by environmental factors, EPCs from both groups were cultured in normal and preeclampsia derived serum conditioned media, respectively.Western blot analysis of histone post translational modifications was performed. Differentiation day of EPCs was significantly delayed (10 days vs 16 days; p<0.05) and the number of OEC colonies were significantly reduced in preeclampsia compared with normal pregnancy. In addition, activity of migration, adhesion and tube formation of OECs was significantly diminished in preeclampsia compared with normal pregnancy. Reduced differentiation potency of EPCs from preeclampsia was not recovered in normal serum while normal EPC was poorly differentiated under preeclampsia derived- serum condition media. Western blot analysis of histone post translational modifications of EPCs demonstrated a significant difference between normal and preeclampsia. In offspring born to preeclampsia, fetal EPCs differentiation potency is epigenetically altered and this in utero programming may be related to increased risk for long-term, adulthood issues such as cardiovascular and metabolic diseases. *This study was supported by National Research Foundation grant (NRF-2017R1D1A1B03029081)