Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPARγ Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells
Abstract
:1. Introduction
2. Results
2.1. Expression of PPARγ and RxRα Is Decreased in the Decidua of PE Placentas
2.2. Correlation of H3K4me3 and H3K9ac with PPARγ and RxRα
2.3. Identification of Decidual Cells Expressing PPARγ/RxRα
2.4. Co-Expression of H3K4me3 and H3K9ac with PPARγ and RxRα
2.5. Specific PPARγ Agonist and Antagonist Regulate H3K4me3 and H3K9ac in Human Trophoblast Cells
3. Discussion
4. Materials and Methods
4.1. Sample—Placental Tissue
4.2. Immunohistochemical Peroxidase Staining
4.3. Double Immunofluorescence Staining of Tissue Slides
4.4. Staining Evaluation
4.5. Isolation of EVT Cells from Placenta Tissue
4.6. FACS of Isolated EVT Cells from Placenta Tissue
4.7. Cell Culture of HVT-Cell Line and Primarily Isolated EVT Cells with PPARγ-Agonist and -Antagonist
4.8. Double Immunofluorescence Staining of Chamber Slides
4.9. Quantitative Analysis of Double Immunofluorescence Staining
4.10. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CK 7 | cytokeratin 7 |
CK 7-PE | phycoerythrin labeled cytokeratin 7 |
Cy2 | cyanine dyes 2 for fluorescence staining |
Cy3 | cyanine dyes 3 for fluorescence staining |
D-PBS | dulbecco’s phosphate buffered saline |
DAB | chromogenic 3,3′-diaminoenzidine |
DAPI | 4′,6-Diamino-2-phenylindile |
DMEM | dulbecco’s Modified Eagle’s Medium |
EDTA | ethylenediaminetetraacetic acid |
EVT | extravillous trophoblast |
FACS | fluorescence-activated cell sorting |
FBS | fetal bovine serum |
FCS | fetal calf serum |
H3K4me3 | trimethylated lysine of the histone H3 |
H3K9ac | acetylated lysine of the histone H3 |
HBSS | Hanks’ balanced salt solution Buffer |
HBSS-HEPES-buffer | Hanks’ balanced salt solution Buffer with 10mM Hepes |
HEPES | 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid |
HRP | horseradish peroxidase |
HVT | human villous trophoblasts, a cell line of cytotrophoblasts |
IRS | Immunoreactive Score |
IUGR | intrauterine growth retardation |
LMU | Ludwig Maximilian University of Munich |
NaCl | sodium chloride |
PBS | phosphate-buffered saline |
PE | preeclampsia (respectively: preeclampsia placentas) |
Pen | penicillin |
PFA | perfluoroalkoxy alkane |
PG | prostaglandins |
PPARγ | peroxisome proliferator-activated receptor gamma |
RPMI-1640 | Roswell Park Memorial Institute 1640 |
RT | room temperature |
RUPP | reduced uterine perfusion pressure |
RxRα | retinoid X receptor alpha |
SD | standard deviation |
SDS-PAGE | sodium dodecyl sulfate polyacrylamide gel electrophoresis |
SEM | standard error of the mean |
Strep | streptomycin |
T0070907 | antagonist of PPARγ |
VEGF | vascular endothelial growth factor |
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H3K4me3 | H3K9ac | |||
---|---|---|---|---|
Syncytium | Decidua | Syncytium | Decidua | |
RxRα syncytium | 0.448 ** 0.002 | 0.513 ** 0.000 | 0.428 ** 0.003 | 0.577 ** 0.000 |
RxRα decidua | 0.406 ** 0.007 | 0.327 * 0.032 | 0.389 ** 0.010 | 0.464 ** 0.002 |
PPARγ syncytium | 0.216 0.131 | 0.249 0.084 | 0.284 * 0.046 | 0.379 ** 0.007 |
PPARγ decidua | 0.357 * 0.012 | 0.227 0.121 | 0.347 * 0.014 | 0.399 ** 0.004 |
Antibody | Species Isotype | Manufacturer | Dilution | |
---|---|---|---|---|
H3K9ac | Rabbit IgG monoclonal (Clone: Y28) | Abcam | 1:200 | IH, IF, IC |
H3K4me3 | Rabbit IgG polyclonal | Abcam | 1:100 | IH, IF, IC |
RxRα | Mouse IgG2a monoclonal (Clone: K8508) | Perseus Proteomics | 1:200 | IH, IF, IC |
PPARγ | Rabbit IgG1 polyclonal | Abcam | 1:100 | IH |
PPARγ | Mouse IgG1 monoclonal (Clone: 8D1H8F4) | Abnova | 1:500 | IC |
PPARγ | Rabbit IgG polyclonal | LSBio | 1:500 | IF |
CK 7 | Mouse IgG1 monoclonal (Clone: NCL-L-CK7-OVTL) | Novocastra | 1:30 | IF |
Cy2 | Goat-Anti-Mouse IgG | Dianova | 1:100 | IF, IC |
Cy3 | Goat-Anti-Rabbit IgG | Dianova | 1:500 | IF, IC |
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Meister, S.; Hahn, L.; Beyer, S.; Paul, C.; Mitter, S.; Kuhn, C.; von Schönfeldt, V.; Corradini, S.; Sudan, K.; Schulz, C.; et al. Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPARγ Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells. Int. J. Mol. Sci. 2021, 22, 12469. https://doi.org/10.3390/ijms222212469
Meister S, Hahn L, Beyer S, Paul C, Mitter S, Kuhn C, von Schönfeldt V, Corradini S, Sudan K, Schulz C, et al. Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPARγ Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells. International Journal of Molecular Sciences. 2021; 22(22):12469. https://doi.org/10.3390/ijms222212469
Chicago/Turabian StyleMeister, Sarah, Laura Hahn, Susanne Beyer, Corinna Paul, Sophie Mitter, Christina Kuhn, Viktoria von Schönfeldt, Stefanie Corradini, Kritika Sudan, Christian Schulz, and et al. 2021. "Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPARγ Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells" International Journal of Molecular Sciences 22, no. 22: 12469. https://doi.org/10.3390/ijms222212469