Hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes.

Autor: Fitzgerald E; Sackler Program for Epigenetics and Psychobiology, McGill University, Montréal, Canada. eamon.fitzgerald@mcgill.ca.; Ludmer Centre for Neuroinformatics and Mental Health, McGill University, Montréal, Canada. eamon.fitzgerald@mcgill.ca.; Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, Canada. eamon.fitzgerald@mcgill.ca., Shen M; Singapore Institute for Clinical Sciences, Agency for Science, Technology & Research, Singapore, Singapore., Yong HEJ; Singapore Institute for Clinical Sciences, Agency for Science, Technology & Research, Singapore, Singapore., Wang Z; Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, Canada., Pokhvisneva I; Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, Canada., Patel S; Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, Canada., O'Toole N; Sackler Program for Epigenetics and Psychobiology, McGill University, Montréal, Canada.; Ludmer Centre for Neuroinformatics and Mental Health, McGill University, Montréal, Canada.; Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, Canada., Chan SY; Singapore Institute for Clinical Sciences, Agency for Science, Technology & Research, Singapore, Singapore.; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Chong YS; Singapore Institute for Clinical Sciences, Agency for Science, Technology & Research, Singapore, Singapore.; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Chen H; KK Women's and Children's Hospital, Singapore, Singapore.; Duke-National University of Singapore, Singapore, Singapore., Gluckman PD; Singapore Institute for Clinical Sciences, Agency for Science, Technology & Research, Singapore, Singapore.; The University of Auckland, Auckland, New Zealand., Chan J; KK Women's and Children's Hospital, Singapore, Singapore.; Duke-National University of Singapore, Singapore, Singapore., Lee PKM; Brain - Body Initiative, Agency for Science, Technology & Research, Singapore, Singapore., Meaney MJ; Sackler Program for Epigenetics and Psychobiology, McGill University, Montréal, Canada. michael.meaney@mcgill.ca.; Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, Canada. michael.meaney@mcgill.ca.; Singapore Institute for Clinical Sciences, Agency for Science, Technology & Research, Singapore, Singapore. michael.meaney@mcgill.ca.; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. michael.meaney@mcgill.ca.; Brain - Body Initiative, Agency for Science, Technology & Research, Singapore, Singapore. michael.meaney@mcgill.ca.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Nov 14; Vol. 14 (1), pp. 7120. Date of Electronic Publication: 2023 Nov 14.
DOI: 10.1038/s41467-023-42300-8
Abstrakt: Pathological placental inflammation increases the risk for several adult disorders, but these mediators are also expressed under homeostatic conditions, where their contribution to adult health outcomes is unknown. Here we define an inflammation-related expression signature, primarily expressed in Hofbauer cells of the term placenta and use expression quantitative trait loci to create a polygenic score (PGS) predictive of its expression. Using this PGS in the UK Biobank we conduct a phenome-wide association study, followed by Mendelian randomization and identify protective, sex-dependent effects of the placental module on cardiovascular and depressive outcomes. Genes differentially regulated by intra-amniotic infection and preterm birth are over-represented within the module. We also identify aspirin as a putative modulator of this inflammation-related signature. Our data support a model where disruption of placental Hofbauer cell function, due to preterm birth or prenatal infection, contributes to the increased risk of depression and cardiovascular disease observed in these individuals.
(© 2023. The Author(s).)
Databáze: MEDLINE
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