{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T18:36:41Z","timestamp":1781807801460,"version":"3.54.5"},"reference-count":46,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Austrian Science Fund (FWF)","award":["P 37161-B"],"award-info":[{"award-number":["P 37161-B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epidural-related maternal fever (ERMF) occurs with significant incidence in women receiving local anesthetics such as ropivacaine via epidural catheter for pain relief during labor. The causal mechanism behind this phenomenon is still not fully resolved, but evidence suggests that these anesthetics cause sterile inflammation. In this observational study, we investigated a possible contributory role of the dual-specificity phosphatase-9 (DUSP9) controlling the activity of mitogen-activated protein kinases (MAPK), and also PH-domain and Leucine-rich repeat phosphatase (PHLPP) regulating AKT kinases. The data show that ropivacaine differentially affects the expression of these phosphatases in distinct cell types of the umbilical cord and placenta. The gene expression of DUSP9 was almost completely switched off in the presence of ropivacaine in HUVECs and extravillous trophoblasts for up to 6 h, while the expression of PHLPP1 was upregulated in HUVECs and syncytiotrophoblasts. Extravillous trophoblasts were identified as a source of pro-inflammatory mediators and regulatory miRNAs in response to ropivacaine. Placentae at term exhibited a distinct DUSP9 expression pattern, whether the patients belonged to the control group or received epidural analgesia with or without elevated body temperature. The observed data imply that ropivacaine induces complex effects on the MAPK and AKT pathways at the feto\u2013maternal interface, which contribute to the ERMF phenomenon.<\/jats:p>","DOI":"10.3390\/ijms26125520","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T09:13:01Z","timestamp":1749460381000},"page":"5520","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cells of the Maternal\u2013Fetal Interface May Contribute to Epidural-Related Maternal Fever After Administration of Ropivacaine: The Role of Phosphatases DUSP9 and PHLPP1"],"prefix":"10.3390","volume":"26","author":[{"given":"Florian","family":"Horn","sequence":"first","affiliation":[{"name":"Clinical Division of General Anesthesia and Intensive Care Medicine, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5910-3053","authenticated-orcid":false,"given":"Verena","family":"Tretter","sequence":"additional","affiliation":[{"name":"Clinical Division of General Anesthesia and Intensive Care Medicine, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Kunihs","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Reproductive Biology Unit, Placental Development Group, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8516-938X","authenticated-orcid":false,"given":"Peter","family":"Wohlrab","sequence":"additional","affiliation":[{"name":"Clinical Division of General Anesthesia and Intensive Care Medicine, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Trimmel","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin A.","family":"Janes","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Djurkic","sequence":"additional","affiliation":[{"name":"Clinical Division of General Anesthesia and Intensive Care Medicine, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meriem","family":"Mekiri","sequence":"additional","affiliation":[{"name":"Clinical Division of General Anesthesia and Intensive Care Medicine, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Kn\u00f6fler","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Reproductive Biology Unit, Placental Development Group, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Reproductive Biology Unit, Placental Development Group, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1213\/ANE.0b013e3181e3a08e","article-title":"Focused review: Ropivacaine versus bupivacaine for epidural labor analgesia","volume":"111","author":"Beilin","year":"2010","journal-title":"Anesth. 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