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Betamethasone administration during pregnancy is associated with placental epigenetic changes with implications for inflammation |
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| Author: | Czamara, Darina1; Dieckmann, Linda1,2; Röh, Simone1; |
| Organizations: |
1Department of Translational Research in Psychiatry, Max-Planck-Institute of Psychiatry, 80804, Munich, Germany 2International Max Planck Research School for Translational Psychiatry, München, Germany 3Institute of Medical Psychology, Charité − Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health (BIH), Luisenstr. 57, 10117, Berlin, Germany
4Department of Experimental Obstetrics, Charité − Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health (BIH), Augustenburger Platz 1, 13353, Berlin, Germany
5Department of Child and Adolescent Psychiatry, Erasmus MC, Sophia Children’s Hospital, Rotterdam, The Netherlands 6Finnish Institute for Health and Welfare, Helsinki, Finland 7Children’s Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland 8Faculty of Medicine, PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland 9Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway 10Institute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Helsinki, Finland 11Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland 12Department of Obstetrics and Gynecology, Tampere University Hospital and Tampere University, Faculty of Medicine and Health Technology, Tampere, Finland 13Department of General Practice and Primary Care, University of Helsinki, Helsinki, Finland 14Folkhälsan Research Center, Helsinki, Finland 15Department of Obstetrics and Gynaecology and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore 16Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore 17Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland 18Department of Obstetrics, Charité − Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health (BIH), Augustenburger Platz 1, 13353, Berlin, Germany 19Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, 30329, USA 20Development, Health, and Disease Research Program, University of California, Irvine, Orange, CA, USA |
| Format: | article |
| Version: | published version |
| Access: | open |
| Online Access: | PDF Full Text (PDF, 1.6 MB) |
| Persistent link: | http://urn.fi/urn:nbn:fi-fe2021110153207 |
| Language: | English |
| Published: |
Springer Nature,
2021
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| Publish Date: | 2021-11-01 |
| Description: |
AbstractBackground: Glucocorticoids (GCs) play a pivotal role in fetal programming. Antenatal treatment with synthetic GCs (sGCs) in individuals in danger of preterm labor is common practice. Adverse short- and long-term effects of antenatal sGCs have been reported, but their effects on placental epigenetic characteristics have never been systematically studied in humans. Results: We tested the association between exposure to the sGC betamethasone (BET) and placental DNA methylation (DNAm) in 52 exposed cases and 84 gestational-age-matched controls. We fine-mapped associated loci using targeted bisulfite sequencing. The association of placental DNAm with gene expression and co-expression analysis on implicated genes was performed in an independent cohort including 494 placentas. Exposure to BET was significantly associated with lower placenta DNAm at an enhancer of FKBP5. FKBP5 (FK506-binding protein 51) is a co-chaperone that modulates glucocorticoid receptor activity. Lower DNAm at this enhancer site was associated with higher expression of FKBP5 and a co-expressed gene module. This module is enriched for genes associated with preeclampsia and involved in inflammation and immune response. Conclusions: Our findings suggest that BET exposure during pregnancy associates with few but lasting changes in placental DNAm and may promote a gene expression profile associated with placental dysfunction and increased inflammation. This may represent a pathway mediating GC-associated negative long-term consequences and health outcomes in offspring. see all
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| Series: |
Clinical epigenetics |
| ISSN: | 1868-7075 |
| ISSN-E: | 1868-7083 |
| ISSN-L: | 1868-7075 |
| Volume: | 13 |
| Issue: | 1 |
| Article number: | 165 |
| DOI: | 10.1186/s13148-021-01153-y |
| OADOI: | https://oadoi.org/10.1186/s13148-021-01153-y |
| Type of Publication: |
A1 Journal article – refereed |
| Field of Science: |
1184 Genetics, developmental biology, physiology |
| Subjects: | |
| Funding: |
AP and TB disclose receipt of financial support for the research, authorship, and/or publication of this article, supported by DFG (BR2925/3-1,-2,-3 and PL241/8-2,-3). EK reports support from Academy of Finland, Foundation for Pediatric Research, Sigrid Juselius Foundation and Novo Nordisk Foundation. Open Access funding enabled and organized by Projekt DEAL. |
| Copyright information: |
© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
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https://creativecommons.org/licenses/by/4.0/ |