Betamethasone administration during pregnancy is associated with placental epigenetic changes with implications for inflammation.

Autor: Czamara D; Department of Translational Research in Psychiatry, Max-Planck-Institute of Psychiatry, 80804, Munich, Germany., Dieckmann L; Department of Translational Research in Psychiatry, Max-Planck-Institute of Psychiatry, 80804, Munich, Germany.; International Max Planck Research School for Translational Psychiatry, München, Germany., Röh S; Department of Translational Research in Psychiatry, Max-Planck-Institute of Psychiatry, 80804, Munich, Germany., Kraemer S; Institute 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., Rancourt RC; Department 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., Sammallahti S; Department of Child and Adolescent Psychiatry, Erasmus MC, Sophia Children's Hospital, Rotterdam, The Netherlands., Kajantie E; Finnish Institute for Health and Welfare, Helsinki, Finland.; Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.; Faculty of Medicine, PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway., Laivuori H; Institute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Helsinki, Finland.; Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.; Department of Obstetrics and Gynecology, Tampere University Hospital and Tampere University, Faculty of Medicine and Health Technology, Tampere, Finland., Eriksson JG; Department of General Practice and Primary Care, University of Helsinki, Helsinki, Finland.; Folkhälsan Research Center, Helsinki, Finland.; Department of Obstetrics and Gynaecology and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Räikkönen K; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Henrich W; Department 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., Plagemann A; Department 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.; Department 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., Binder EB; Department of Translational Research in Psychiatry, Max-Planck-Institute of Psychiatry, 80804, Munich, Germany.; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, 30329, USA., Braun T; Department 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.; Department 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., Entringer S; Institute 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. sonja.entringer@charite.de.; Development, Health, and Disease Research Program, University of California, Irvine, Orange, CA, USA. sonja.entringer@charite.de.
Jazyk: angličtina
Zdroj: Clinical epigenetics [Clin Epigenetics] 2021 Aug 26; Vol. 13 (1), pp. 165. Date of Electronic Publication: 2021 Aug 26.
DOI: 10.1186/s13148-021-01153-y
Abstrakt: Background: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje