Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPAR gamma Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells

Meister, Sarah; Hahn, Laura; Beyer, Susanne; Paul, Corinna; Mitter, Sophie; Kuhn, Christina; Schoenfeldt, Viktoria von; Corradini, Stefanie; Sudan, Kritika; Schulz, Christian; Kolben, Theresa Maria; Mahner, Sven; Jeschke, Udo und Kolben, Thomas (2021): Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPAR gamma Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells. In: International Journal of Molecular Sciences, Bd. 22, Nr. 22, 12469

Abstract

The aim of this study was to analyze the expression of peroxisome proliferator-activated receptor gamma (PPAR gamma) and retinoid X receptor alpha (RxR alpha), a binding heterodimer playing a pivotal role in the successful trophoblast invasion, in the placental tissue of preeclamptic patients. Furthermore, we aimed to characterize a possible interaction between PPAR gamma and H3K4me3 (trimethylated lysine 4 of the histone H3), respectively H3K9ac (acetylated lysine 9 of the histone H3), to illuminate the role of histone modifications in a defective trophoblast invasion in preeclampsia (PE). Therefore, the expression of PPAR gamma and RxR alpha was analyzed in 26 PE and 25 control placentas by immunohistochemical peroxidase staining, as well as the co-expression with H3K4me3 and H3K9ac by double immunofluorescence staining. Further, the effect of a specific PPAR gamma-agonist (Ciglitazone) and PPAR gamma-antagonist (T0070907) on the histone modifications H3K9ac and H3K4me3 was analyzed in vitro. In PE placentas, we found a reduced expression of PPAR gamma and RxR alpha and a reduced co-expression with H3K4me3 and H3K9ac in the extravillous trophoblast (EVT). Furthermore, with the PPAR gamma-antagonist treated human villous trophoblast (HVT) cells and primary isolated EVT cells showed higher levels of the histone modification proteins whereas treatment with the PPAR gamma-agonist reduced respective histone modifications. Our results show that the stimulation of PPAR gamma-activity leads to a reduction of H3K4me3 and H3K9ac in trophoblast cells, but paradoxically decreases the nuclear PPAR gamma expression. As the importance of PPAR gamma, being involved in a successful trophoblast invasion has already been investigated, our results reveal a pathophysiologic connection between PPAR gamma and the epigenetic modulation via H3K4me3 and H3K9ac in PE.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch