{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:18:15Z","timestamp":1785406695814,"version":"3.56.0"},"posted":{"date-parts":[[2026,3,12]]},"group-title":"Developmental Biology","reference-count":44,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"crossref","award":["5R01NS126981"],"award-info":[{"award-number":["5R01NS126981"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"award":["A2019279S"],"award-info":[{"award-number":["A2019279S"]}],"id":[{"id":"https:\/\/ror.org\/03cvfxv40","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007625","name":"Cure Alzheimer\u2019s Fund","doi-asserted-by":"crossref","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100007625","id-type":"DOI","asserted-by":"crossref"}]},{"name":"CIRM","award":["EDUC4-12802"],"award-info":[{"award-number":["EDUC4-12802"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Maternal inflammation during pregnancy is a major risk factor for adverse neurodevelopmental outcomes, yet the mechanisms linking maternal immune activation (MIA) to placenta\u2013fetal brain axis dysfunction remain unclear. Using a poly-(I:C) mouse model, we show that MIA rapidly disrupts placental-blood barrier (PBB) integrity by disrupting pericyte\u2013endothelium coupling within 48 hours, leading to increased placental permeability detected by in vivo MRI. We identify a prostaglandin E2 (PGE2)-dependent pathway involving cyclooxygenase-2 (COX2) and prostaglandin E-synthase (mPGES1) as a key mediator of this effect. Pharmacological inhibition of COX2 prevented MIA-induced structural and functional changes. In vitro explant studies confirmed that PGE2 acts via the EP3 receptor to disrupt pericyte\u2013endothelium interactions, while ex vivo perfusion demonstrated that in addition to its local effects on PBB structure, placenta-derived PGE2 enters the fetal circulation. Finally, similar vascular alterations were observed in human placentas from pregnancies with severe maternal inflammation. These findings reveal a conserved inflammatory mechanism that compromises PBB integrity and may relay signals to the fetal brain, highlighting potential therapeutic targets for neuroprotection during prenatal inflammation.<\/jats:p>\n                <jats:sec>\n                  <jats:title>One Sentence Summary<\/jats:title>\n                  <jats:p>Maternal immune activation during pregnancy disrupts placental vascular integrity through a COX2-dependent prostaglandin E2 pathway, which compromises the placenta\u2013blood barrier and relays inflammatory signals to the fetus, identifying potential therapeutic targets for neuroprotection.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.11.706681","type":"posted-content","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T14:05:14Z","timestamp":1773324314000},"source":"Crossref","is-referenced-by-count":1,"title":["Placental prostaglandin signaling disrupts barrier integrity and relays an acute inflammatory signal to the fetus"],"prefix":"10.64898","author":[{"given":"Hana","family":"Horackova","sequence":"first","affiliation":[{"name":"The Saban Research Institute, Children\u2019s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California 90027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuying","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Saban Research Institute, Children\u2019s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California 90027, USA"},{"name":"UCLA Brain Research & Artificial Intelligence Nexus, Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakeela","family":"Faulkner","sequence":"additional","affiliation":[{"name":"Division of Maternal-Fetal Medicine, Department of Obstetrics and 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Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California 90027, USA"},{"name":"Programs in Biomedical and Biological Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"Crosthwait","sequence":"additional","affiliation":[{"name":"The Saban Research Institute, Children\u2019s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California 90027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiye","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Skaggs Graduate School of Chemical and Biological Sciences, The Scripps Research Institute, La Jolla, California 92037, 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Dean","family":"Wallace","sequence":"additional","affiliation":[{"name":"Department of Pathology, Keck School of Medicine, University of Southern California. Los Angeles, California 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saloni","family":"Walia","sequence":"additional","affiliation":[{"name":"Department of Pathology, Keck School of Medicine, University of Southern California. 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