{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:18:36Z","timestamp":1789625916618,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T00:00:00Z","timestamp":1769212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS","award":["DN00271"],"award-info":[{"award-number":["DN00271"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: Maternal immune activation (MIA) increases the risk of Autism Spectrum Disorders (ASD). Experimental models demonstrate that maternal exposure to bacterial endotoxin or the viral mimic polyinosinic:polycytidylic acid [poly (I:C)] reliably recapitulates ASD-like behavioral abnormalities in offspring, yet the underlying neurobiological mechanisms linking MIA to altered neurodevelopment remain incompletely understood. Increasing evidence highlights the placenta as a critical mediator in shaping fetal brain development through immunological and hormonal regulation. Likewise, disruption of placental regulatory functions upon MIA may therefore represent a mechanistic pathway. Here, we investigated how alterations in placental cytokine profiles, innate immune cell composition, and endocrine outputs relate to neuroinflammation and neurogenesis in the offspring. Methods: Pregnant mice at gestational day 12.5 received a single intraperitoneal injection of poly (I:C). Placental macrophages, neutrophils, inflammatory cytokines, and nerve growth factor (NGF) expression were examined 72 h later. Neurodevelopmental outcomes, including microglial activity and neurogenic markers, were evaluated in mouse offspring at postnatal day (P) 1 and 6. Results: MIA induced a significant accumulation of monocytes and neutrophils in the placenta, which was associated with elevated levels of a broad spectrum of inflammatory mediators, including Th17-biased proinflammatory cytokines, chemokines, and adhesion proteins, in the placenta and amniotic fluid. In contrast, the placenta-derived NGF levels were significantly reduced. MIA induced strong and sustained microglial activation in the fetal and neonatal brain. This inflammatory milieu was accompanied by disrupted cortical neurogenesis, characterized by a marked increase in Ki67+ neuronal progenitor cells (NPCs) in the subventricular zone (SVZ), overproduction of early-born Tbr1+ neurons at P1, later-born Satb2+ neurons at P6. Conclusions: Collectively, these findings suggest that heightened Th17 inflammatory signaling, coupled with impaired placental endocrine function, contributes to dysregulated cortical neurogenesis in the offspring.<\/jats:p>","DOI":"10.3390\/brainsci16020126","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T08:14:23Z","timestamp":1769415263000},"page":"126","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Maternal Poly (I:C)-Induced Placental Inflammation and Endocrine Dysfunction Are Associated with Disrupted Corticogenesis in Mouse Offspring"],"prefix":"10.3390","volume":"16","author":[{"given":"Catherine","family":"Zhou","sequence":"first","affiliation":[{"name":"Summer Undergraduate Research Program, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7359-354X","authenticated-orcid":false,"given":"Callan","family":"Baldwin","sequence":"additional","affiliation":[{"name":"Summer Undergraduate Research Program, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuying","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Hayes","sequence":"additional","affiliation":[{"name":"Summer Undergraduate Research Program, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1016-0019","authenticated-orcid":false,"given":"Kathleen","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lir-Wan","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9928-4036","authenticated-orcid":false,"given":"Abhay","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0453-6921","authenticated-orcid":false,"given":"Yi","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16928","DOI":"10.1038\/s41598-019-53294-z","article-title":"Maternal and Early Postnatal Immune Activation Produce Sex-Specific Effects on Autism-Like Behaviors and Neuroimmune Function in Mice","volume":"9","author":"Carlezon","year":"2019","journal-title":"Sci. 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