{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T22:19:38Z","timestamp":1778710778925,"version":"3.51.4"},"reference-count":108,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2019,10,10]],"date-time":"2019-10-10T00:00:00Z","timestamp":1570665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003549","name":"Hungarian Scientific Research Fund","doi-asserted-by":"publisher","award":["K128262"],"award-info":[{"award-number":["K128262"]}],"id":[{"id":"10.13039\/501100003549","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003549","name":"Hungarian Scientific Research Fund","doi-asserted-by":"publisher","award":["K124862"],"award-info":[{"award-number":["K124862"]}],"id":[{"id":"10.13039\/501100003549","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003825","name":"Magyar Tudom\u00e1nyos Akad\u00e9mia","doi-asserted-by":"publisher","award":["Momentum LP2014-7\/2014"],"award-info":[{"award-number":["Momentum LP2014-7\/2014"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003825","name":"Magyar Tudom\u00e1nyos Akad\u00e9mia","doi-asserted-by":"publisher","award":["Medinprot Protein Science Research Synergy IV and Adhoc Program grants"],"award-info":[{"award-number":["Medinprot Protein Science Research Synergy IV and Adhoc Program grants"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003825","name":"Magyar Tudom\u00e1nyos Akad\u00e9mia","doi-asserted-by":"publisher","award":["Premium_2019-436 grant"],"award-info":[{"award-number":["Premium_2019-436 grant"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003825","name":"Magyar Tudom\u00e1nyos Akad\u00e9mia","doi-asserted-by":"publisher","award":["Young Research Fellowships"],"award-info":[{"award-number":["Young Research Fellowships"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hungarian National Research, Development and Innovation Office","award":["FIEK_16-1-2016-0005"],"award-info":[{"award-number":["FIEK_16-1-2016-0005"]}]},{"name":"Hungarian Ministry for National Economy","award":["VEKOP-2.3.3-15-2017-0014"],"award-info":[{"award-number":["VEKOP-2.3.3-15-2017-0014"]}]},{"name":"Gynecologic Oncology Research Fund","award":["USC"],"award-info":[{"award-number":["USC"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gene expression studies of molar pregnancy have been limited to a small number of candidate loci. We analyzed high-dimensional RNA and protein data to characterize molecular features of complete hydatidiform moles (CHMs) and corresponding pathologic pathways. CHMs and first trimester placentas were collected, histopathologically examined, then flash-frozen or paraffin-embedded. Frozen CHMs and control placentas were subjected to RNA-Seq, with resulting data and published placental RNA-Seq data subjected to bioinformatics analyses. Paraffin-embedded tissues from CHMs and control placentas were used for tissue microarray (TMA) construction, immunohistochemistry, and immunoscoring for galectin-14. Of the 14,022 protein-coding genes expressed in all samples, 3,729 were differentially expressed (DE) in CHMs, of which 72% were up-regulated. DE genes were enriched in placenta-specific genes (OR = 1.88, p = 0.0001), of which 79% were down-regulated, imprinted genes (OR = 2.38, p = 1.54 \u00d7 10\u22126), and immune genes (OR = 1.82, p = 7.34 \u00d7 10\u221218), of which 73% were up-regulated. DNA methylation-related enzymes and histone demethylases were dysregulated. \u201cCytokine\u2013cytokine receptor interaction\u201d was the most impacted of 38 dysregulated pathways, among which 17 were immune-related pathways. TMA-based immunoscoring validated the lower expression of galectin-14 in CHM. In conclusion, placental functions were down-regulated, imprinted gene expression was altered, and immune pathways were activated, indicating complex dysregulation of placental developmental and immune processes in CHMs.<\/jats:p>","DOI":"10.3390\/ijms20204999","type":"journal-article","created":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T03:07:11Z","timestamp":1570763231000},"page":"4999","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Dysregulation of Placental Functions and Immune Pathways in Complete Hydatidiform Moles"],"prefix":"10.3390","volume":"20","author":[{"given":"Jennifer R.","family":"King","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7785-4221","authenticated-orcid":false,"given":"Melissa L.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Szabolcs","family":"Hetey","sequence":"additional","affiliation":[{"name":"Systems Biology of Reproduction Research Group, Institute of Enzymology, Research Centre for Natural Sciences, H-1117 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Kiraly","sequence":"additional","affiliation":[{"name":"Systems Biology of Reproduction Research Group, Institute of Enzymology, Research Centre for Natural Sciences, H-1117 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6232-8701","authenticated-orcid":false,"given":"Koji","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio V.","family":"Castaneda","sequence":"additional","affiliation":[{"name":"Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7149-1482","authenticated-orcid":false,"given":"Eszter","family":"Toth","sequence":"additional","affiliation":[{"name":"Systems Biology of Reproduction Research Group, Institute of Enzymology, Research Centre for Natural Sciences, H-1117 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9164-065X","authenticated-orcid":false,"given":"Tibor","family":"Krenacs","sequence":"additional","affiliation":[{"name":"First Department of Pathology and Experimental Cancer Research, Semmelweis University, H-1085 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petronella","family":"Hupuczi","sequence":"additional","affiliation":[{"name":"Maternity Private Clinic of Obstetrics and Gynecology, H-1126 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulette","family":"Mhawech-Fauceglia","sequence":"additional","affiliation":[{"name":"Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0322-1522","authenticated-orcid":false,"given":"Andrea","family":"Balogh","sequence":"additional","affiliation":[{"name":"Systems Biology of Reproduction Research Group, Institute of Enzymology, Research Centre for Natural Sciences, H-1117 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1773-6861","authenticated-orcid":false,"given":"Andras","family":"Szilagyi","sequence":"additional","affiliation":[{"name":"Systems Biology of Reproduction Research Group, Institute of Enzymology, Research Centre for Natural Sciences, H-1117 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9434-934X","authenticated-orcid":false,"given":"Janos","family":"Matko","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biology, Eotvos Lorand University, H-1117 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7532-9703","authenticated-orcid":false,"given":"Zoltan","family":"Papp","sequence":"additional","affiliation":[{"name":"Maternity Private Clinic of Obstetrics and Gynecology, H-1126 Budapest, Hungary"},{"name":"Department of Obstetrics and Gynecology, Semmelweis University, H-1088 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6960-4414","authenticated-orcid":false,"given":"Lynda D.","family":"Roman","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2339-1089","authenticated-orcid":false,"given":"Victoria 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H-1126 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.ajog.2010.06.073","article-title":"Gestational trophoblastic disease I: Epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole","volume":"203","author":"Lurain","year":"2010","journal-title":"Am. 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