{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T20:38:35Z","timestamp":1791837515386,"version":"4.3.4"},"reference-count":77,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:00:00Z","timestamp":1637193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB 914 project A10"],"award-info":[{"award-number":["SFB 914 project A10"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The aim of this study was to analyze the expression of peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3) and retinoid X receptor \u03b1 (RxR\u03b1), 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\u03b3 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\u03b3 and RxR\u03b1 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\u03b3-agonist (Ciglitazone) and PPAR\u03b3-antagonist (T0070907) on the histone modifications H3K9ac and H3K4me3 was analyzed in vitro. In PE placentas, we found a reduced expression of PPAR\u03b3 and RxR\u03b1 and a reduced co-expression with H3K4me3 and H3K9ac in the extravillous trophoblast (EVT). Furthermore, with the PPAR\u03b3-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\u03b3-agonist reduced respective histone modifications. Our results show that the stimulation of PPAR\u03b3-activity leads to a reduction of H3K4me3 and H3K9ac in trophoblast cells, but paradoxically decreases the nuclear PPAR\u03b3 expression. As the importance of PPAR\u03b3, being involved in a successful trophoblast invasion has already been investigated, our results reveal a pathophysiologic connection between PPAR\u03b3 and the epigenetic modulation via H3K4me3 and H3K9ac in PE.<\/jats:p>","DOI":"10.3390\/ijms222212469","type":"journal-article","created":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T02:43:09Z","timestamp":1637289789000},"page":"12469","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPAR\u03b3 Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells"],"prefix":"10.3390","volume":"22","author":[{"given":"Sarah","family":"Meister","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3119-6053","authenticated-orcid":false,"given":"Laura","family":"Hahn","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Beyer","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8510-6263","authenticated-orcid":false,"given":"Corinna","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Mitter","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Kuhn","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Augsburg, 86156 Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoria","family":"von Sch\u00f6nfeldt","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8709-7252","authenticated-orcid":false,"given":"Stefanie","family":"Corradini","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kritika","family":"Sudan","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, Klinikum der Universit\u00e4t M\u00fcnchen LMU Munich, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8149-0747","authenticated-orcid":false,"given":"Christian","family":"Schulz","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, Klinikum der Universit\u00e4t M\u00fcnchen LMU Munich, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa Maria","family":"Kolben","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Mahner","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2623-3235","authenticated-orcid":false,"given":"Udo","family":"Jeschke","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany"},{"name":"Department of Gynecology and Obstetrics, University Hospital Augsburg, 86156 Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1418-8588","authenticated-orcid":false,"given":"Thomas","family":"Kolben","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Apicella, C., Ruano, C.S.M., M\u00e9hats, C., Miralles, F., and Vaiman, D. 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