Hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes
Abstract 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 expre...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42300-8 |
| _version_ | 1797557867332501504 |
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| author | Eamon Fitzgerald Mojun Shen Hannah Ee Juen Yong Zihan Wang Irina Pokhvisneva Sachin Patel Nicholas O’Toole Shiao-Yng Chan Yap Seng Chong Helen Chen Peter D. Gluckman Jerry Chan Patrick Kia Ming Lee Michael J. Meaney |
| author_facet | Eamon Fitzgerald Mojun Shen Hannah Ee Juen Yong Zihan Wang Irina Pokhvisneva Sachin Patel Nicholas O’Toole Shiao-Yng Chan Yap Seng Chong Helen Chen Peter D. Gluckman Jerry Chan Patrick Kia Ming Lee Michael J. Meaney |
| author_sort | Eamon Fitzgerald |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-10T17:22:22Z |
| format | Article |
| id | doaj.art-562ebed74c8f4dc0a29125be9a4443f5 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:22:22Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-562ebed74c8f4dc0a29125be9a4443f52023-11-20T10:17:35ZengNature PortfolioNature Communications2041-17232023-11-0114111110.1038/s41467-023-42300-8Hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomesEamon Fitzgerald0Mojun Shen1Hannah Ee Juen Yong2Zihan Wang3Irina Pokhvisneva4Sachin Patel5Nicholas O’Toole6Shiao-Yng Chan7Yap Seng Chong8Helen Chen9Peter D. Gluckman10Jerry Chan11Patrick Kia Ming Lee12Michael J. Meaney13Sackler Program for Epigenetics and Psychobiology, McGill UniversitySingapore Institute for Clinical Sciences, Agency for Science, Technology & ResearchSingapore Institute for Clinical Sciences, Agency for Science, Technology & ResearchDouglas Mental Health University Institute, Department of Psychiatry, McGill UniversityDouglas Mental Health University Institute, Department of Psychiatry, McGill UniversityDouglas Mental Health University Institute, Department of Psychiatry, McGill UniversitySackler Program for Epigenetics and Psychobiology, McGill UniversitySingapore Institute for Clinical Sciences, Agency for Science, Technology & ResearchSingapore Institute for Clinical Sciences, Agency for Science, Technology & ResearchKK Women’s and Children’s HospitalSingapore Institute for Clinical Sciences, Agency for Science, Technology & ResearchKK Women’s and Children’s HospitalBrain – Body Initiative, Agency for Science, Technology & ResearchSackler Program for Epigenetics and Psychobiology, McGill UniversityAbstract 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.https://doi.org/10.1038/s41467-023-42300-8 |
| spellingShingle | Eamon Fitzgerald Mojun Shen Hannah Ee Juen Yong Zihan Wang Irina Pokhvisneva Sachin Patel Nicholas O’Toole Shiao-Yng Chan Yap Seng Chong Helen Chen Peter D. Gluckman Jerry Chan Patrick Kia Ming Lee Michael J. Meaney Hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes Nature Communications |
| title | Hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes |
| title_full | Hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes |
| title_fullStr | Hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes |
| title_full_unstemmed | Hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes |
| title_short | Hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes |
| title_sort | hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes |
| url | https://doi.org/10.1038/s41467-023-42300-8 |
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