Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPARγ Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells
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 t...
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oai:doaj.org-article:a071b30b3eea40f7a51158b310dd17952021-11-25T17:56:56ZRegulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPARγ Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells10.3390/ijms2222124691422-00671661-6596https://doaj.org/article/a071b30b3eea40f7a51158b310dd17952021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12469https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The 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). 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. 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. 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.Sarah MeisterLaura HahnSusanne BeyerCorinna PaulSophie MitterChristina KuhnViktoria von SchönfeldtStefanie CorradiniKritika SudanChristian SchulzTheresa Maria KolbenSven MahnerUdo JeschkeThomas KolbenMDPI AGarticlepreeclampsiahistone modificationH3K4me3H3K9acPPARγRxRαBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12469, p 12469 (2021) |
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| topic |
preeclampsia histone modification H3K4me3 H3K9ac PPARγ RxRα Biology (General) QH301-705.5 Chemistry QD1-999 |
| spellingShingle |
preeclampsia histone modification H3K4me3 H3K9ac PPARγ RxRα Biology (General) QH301-705.5 Chemistry QD1-999 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 Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPARγ Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells |
| description |
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). 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. 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. 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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Sarah Meister |
| title |
Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPARγ Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells |
| title_short |
Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPARγ Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells |
| title_full |
Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPARγ Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells |
| title_fullStr |
Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPARγ Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells |
| title_full_unstemmed |
Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPARγ Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells |
| title_sort |
regulation of epigenetic modifications in the placenta during preeclampsia: pparγ influences h3k4me3 and h3k9ac in extravillous trophoblast cells |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/a071b30b3eea40f7a51158b310dd1795 |
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