Sarah Meister, Laura Hahn, Susanne Beyer, Corinna Paul, Sophie Mitter, Christina Kuhn, Viktoria von Schönfeldt, Stefanie Corradini, Kritika Sudan, Christian Schulz, Theresa Maria Kolben, Sven Mahner, Udo Jeschke, Thomas Kolben
- Problem
Preeclampsia is a severe pregnancy disorder with high mortality and morbidity. The only known curative therapy is the delivery of the baby. Therefore, gaining knowledge of the pathophysiological causes is essential. The aim of this study was to analyze the expression of peroxisome proliferator‐activated receptor γ (PPARγ) and retinoid X receptor α (RxRα), 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 PPARγ 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).
Methods of study
Therefore, the expression of PPARγ and RxRα was analyzed in 26 PE and 25 control placentas by immunohistochemical peroxidase staining, as well as the co‐expression with H3K4me3Problem
Preeclampsia is a severe pregnancy disorder with high mortality and morbidity. The only known curative therapy is the delivery of the baby. Therefore, gaining knowledge of the pathophysiological causes is essential. The aim of this study was to analyze the expression of peroxisome proliferator‐activated receptor γ (PPARγ) and retinoid X receptor α (RxRα), 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 PPARγ 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).
Methods of study
Therefore, the expression of PPARγ and RxRα 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 PPARγ‐agonist (Ciglitazone) and PPARγ‐antagonist (T0070907) on the histone modifications H3K9ac and H3K4me3 was analyzed in vitro.
Results
In PE placentas, we found a reduced expression of PPARγ and RxRα and a reduced co‐expression with H3K4me3 and H3K9ac in the extravillous trophoblast (EVT). Furthermore, with the PPARγ‐antagonist treated human villous trophoblast (HVT) cells and primary isolated EVT cells showed higher levels of the histone modification proteins whereas treatment with the PPARγ‐agonist reduced respective histone modifications.
Conclusion
Our results show that the stimulation of PPARγ‐activity leads to a reduction of H3K4me3 and H3K9ac in trophoblast cells, but paradoxically decreases the nuclear PPARγ expression. As the importance of PPARγ, being involved in a successful trophoblast invasion has already been investigated, our results reveal a pathophysiologic connection between PPARγ and the epigenetic modulation via H3K4me3 and H3K9ac in PE.…
