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de Desarrollo Cient\u00edfico y Tecnol\u00f3gico FONDECYT","award":["FS\/15\/32\/31604"],"award-info":[{"award-number":["FS\/15\/32\/31604"]}]},{"name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico FONDECYT","award":["1190250"],"award-info":[{"award-number":["1190250"]}]},{"name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico FONDECYT","award":["1180935"],"award-info":[{"award-number":["1180935"]}]},{"name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico FONDECYT","award":["1221362"],"award-info":[{"award-number":["1221362"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Preeclampsia (PE) is a pregnancy-specific disorder that affects 3 to 5% of pregnancies worldwide and is one of the leading causes of maternal and fetal morbidity and mortality. Nevertheless, how these events occur remains unclear. We hypothesized that the induction of hypoxic conditions in vitro in primary human trophoblast cells would mimic several characteristics of PE found in vivo. We applied and characterized a model of primary cytotrophoblasts isolated from healthy pregnancies that were placed under different oxygen concentrations: ambient O2 (5% pCO2, 21%pO2, 24 h, termed \u201cnormoxia\u201d), low O2 concentration (5% pCO2, 1.5% pO2, 24 h, termed \u201chypoxia\u201d), or \u201chypoxia\/reoxygenation\u201d (H\/R: 6 h intervals of normoxia and hypoxia for 24 h). Various established preeclamptic markers were assessed in this cell model and compared to placental tissues obtained from PE pregnancies. Seventeen PE markers were analyzed by qPCR, and the protein secretion of soluble fms-like tyrosine kinase 1 (sFlT-1) and the placenta growth factor (PlGF) was determined by ELISA. Thirteen of seventeen genes associated with angiogenesis, the renin\u2013angiotensin system, oxidative stress, endoplasmic reticulum stress, and the inflammasome complex were susceptible to H\/R and hypoxia, mimicking the expression pattern of PE tissue. In cell culture supernatants, the secretion of sFlT-1 was increased in hypoxia, while PlGF release was significantly reduced in H\/R and hypoxia. In the supernatants of our cell models, the sFlT-1\/PlGF ratio in hypoxia and H\/R was higher than 38, which is a strong indicator for PE in clinical practice. These results suggest that our cellular models reflect important pathological processes occurring in PE and are therefore suitable as PE in vitro models.<\/jats:p>","DOI":"10.3390\/cells11121898","type":"journal-article","created":{"date-parts":[[2022,6,11]],"date-time":"2022-06-11T09:33:26Z","timestamp":1654940006000},"page":"1898","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Primary Human Trophoblasts Mimic the Preeclampsia Phenotype after Acute Hypoxia\u2013Reoxygenation Insult"],"prefix":"10.3390","volume":"11","author":[{"given":"Barbara","family":"Fuenzalida","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Molecular Medicine, Faculty of Medicine, University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sampada","family":"Kallol","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Medicine, Faculty of Medicine, University of Bern, 3012 Bern, Switzerland"},{"name":"Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3153-2806","authenticated-orcid":false,"given":"Jonas","family":"Zaugg","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Medicine, Faculty of Medicine, University of Bern, 3012 Bern, Switzerland"},{"name":"Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5594-0532","authenticated-orcid":false,"given":"Martin","family":"Mueller","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Inselspital, University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2564-7348","authenticated-orcid":false,"given":"Hiten D.","family":"Mistry","sequence":"additional","affiliation":[{"name":"Department of Women and Children\u2019s Health, School of Life Course and Population Health Sciences, King\u2019s College London, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"School of Medical Technology, Faculty of Medicine and Sciences Health, Universidad San Sebasti\u00e1n, Santiago 7510157, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7349-5380","authenticated-orcid":false,"given":"Andrea","family":"Leiva","sequence":"additional","affiliation":[{"name":"School of Medical Technology, Faculty of Medicine and Sciences Health, Universidad San Sebasti\u00e1n, Santiago 7510157, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7846-6930","authenticated-orcid":false,"given":"Christiane","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Medicine, Faculty of Medicine, University of Bern, 3012 Bern, Switzerland"},{"name":"Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1053\/j.semperi.2011.09.011","article-title":"Maternal Mortality From Preeclampsia\/Eclampsia","volume":"36","author":"Ghulmiyyah","year":"2012","journal-title":"Semin. 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