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Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPARγ Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 Nov 18; Vol. 22 (22). Date of Electronic Publication: 2021 Nov 18. - Publication Year :
- 2021
-
Abstract
- 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.
- Subjects :
- Adult
Benzamides pharmacology
Case-Control Studies
Female
Histones metabolism
Humans
Methylation drug effects
PPAR gamma agonists
PPAR gamma antagonists & inhibitors
PPAR gamma metabolism
Pre-Eclampsia metabolism
Pre-Eclampsia pathology
Pregnancy
Protein Isoforms genetics
Protein Isoforms metabolism
Pyridines pharmacology
Retinoid X Receptor alpha metabolism
Signal Transduction
Thiazolidinediones pharmacology
Trophoblasts drug effects
Trophoblasts pathology
Epigenesis, Genetic
Histones genetics
PPAR gamma genetics
Pre-Eclampsia genetics
Retinoid X Receptor alpha genetics
Trophoblasts metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 34830351
- Full Text :
- https://doi.org/10.3390/ijms222212469