Maternal serum from 'high-stress' pregnancies demonstrates bioactivity capable of attenuating neurite growth through a TNFα-dependent pathway in SH-SY5Y cells

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dc.contributor.authorDeady, Clara
dc.contributor.authorWilmes, Lars
dc.contributor.authorMcCarthy, Fergus P.
dc.contributor.authorKhashan, Ali S.
dc.contributor.authorClarke, Gerard
dc.contributor.authorKeane, James
dc.contributor.authorMcCarthy, Cathal
dc.contributor.authorO’Keeffe, Gerard W.
dc.contributor.authorO’Mahony, Siobhain M.
dc.contributor.funderTaighde Éireann - Research Ireland
dc.date.accessioned2026-07-08T15:00:01Z
dc.date.available2026-07-08T15:00:01Z
dc.date.issued2026-06-18
dc.description.abstractPrenatal stress is associated with deleterious neurodevelopmental consequences in affected offspring. Prenatal stress via exposure to high physiological levels of inflammation in utero may induce an inflammatory state in the fetal brain. However, inflammation is not only associated with disease-states but also can be seen in a healthy pregnancy. There is limited research examining the potential that exposure to biological mediators of stress may have on neurodevelopment. We aim to determine whether certain circulating biological markers in maternal serum influence neurite growth in partially differentiated SH-SY5Y cells as a potential mechanism impacting neurodevelopment. Blood was collected at 20-weeks' gestation as part of the SCOPE pregnancy cohort study. These factors, including pro-inflammatory cytokines, markers of tryptophan metabolism, and gut permeability that were previously analysed, were used to stratify women into low (n = 10) and high (n = 10) biological stress groups. Exposure to the serum categorised as 'high-stress' significantly reduced neurite length in comparison to serum categorised as 'low-stress', with tumour necrosis factor-α playing a substantial role in mediating this reduction. The 'high-stress' serum was subsequently found to increase the levels of phospho-Ser536-p65. Phosphorylation of p65 Ser536 has previously been shown to switch NF-κΒ from promoting neuronal growth, to inhibiting it. The reduction in neurite length seen following exposure to the 'high-stress' serum was prevented when NF-κΒ p65 was knocked down. The present study emphasises the potential negative impact that circulating factors may have on neuronal growth, and the mechanism behind it.en
dc.description.sponsorshipThe present work was funded by Research Ireland (GOIPG/2022/426).
dc.description.versionPublished Version
dc.format.extent12
dc.format.mimetypeapplication/pdfen
dc.identifier.articleidBSR20260125
dc.identifier.authororcidDeady, Clara
dc.identifier.authororcidWilmes, Lars
dc.identifier.authororcidMcCarthy, Fergus P.§0000-0001-5062-6851
dc.identifier.authororcidKhashan, Ali S.
dc.identifier.authororcidClarke, Gerard§0000-0001-9771-3979
dc.identifier.authororcidKeane, James
dc.identifier.authororcidMcCarthy, Cathal§0000-0002-9514-9021
dc.identifier.authororcidO’Keeffe, Gerard W.§0000-0001-5149-0933
dc.identifier.authororcidO’Mahony, Siobhain M.
dc.identifier.citationDeady, C, Wilmes, L, McCarthy, F P, Khashan, A S, Clarke, G, Keane, J, McCarthy, C, O’Keeffe, G W & O’Mahony, S M 2026, 'Maternal serum from 'high-stress' pregnancies demonstrates bioactivity capable of attenuating neurite growth through a TNFα-dependent pathway in SH-SY5Y cells', Bioscience Reports, vol. 46, no. 7, BSR20260125, pp. 1-12. https://doi.org/10.1042/BSR20260125
dc.identifier.doi10.1042/BSR20260125
dc.identifier.endpage12
dc.identifier.issn0144-8463
dc.identifier.issued7
dc.identifier.journaltitleBioscience Reports
dc.identifier.otherPubMedCentral: PMC13279720
dc.identifier.otherORCID: /0000-0002-9514-9021/work/220111457
dc.identifier.otherORCID: /0000-0001-5062-6851/work/220111671
dc.identifier.otherORCID: /0000-0001-5149-0933/work/220112120
dc.identifier.startpage1
dc.identifier.urihttps://hdl.handle.net/10468/19029
dc.identifier.volume46
dc.language.isoen
dc.publisherPortland Press Ltd
dc.relation.urihttps://www.scopus.com/pages/publications/105043422465
dc.rights© 2026 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY)
dc.rights.accessrightsopen access
dc.rights.licensenameAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.statusPeer reviewed
dc.subjectAdult
dc.subjectCell Line, Tumor
dc.subjectFemale
dc.subjectHumans
dc.subjectNeurites/metabolism
dc.subjectNeurodevelopment
dc.subjectPhosphorylation
dc.subjectPregnancy
dc.subjectSignal Transduction
dc.subjectStress, Physiological
dc.subjectTranscription Factor RelA/metabolism
dc.subjectTumor Necrosis Factor-alpha/blood
dc.subject[APCMicrobiome]
dc.subject[INFANT]
dc.subject[Medicine]
dc.subject[PublicHealth]
dc.titleMaternal serum from 'high-stress' pregnancies demonstrates bioactivity capable of attenuating neurite growth through a TNFα-dependent pathway in SH-SY5Y cellsen
dc.typeArticle (peer-reviewed)
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