Sex differences in DNA methylation across gestation: a large scale, cross-cohort, multi-tissue analysis.

Autor: Czamara D; Department Genes and Environment, Max Planck Institute of Psychiatry, Munich, Germany. darina@psych.mpg.de., Dieckmann L; Department Genes and Environment, Max Planck Institute of Psychiatry, Munich, Germany.; International Max Planck Research School for Translational Psychiatry, Munich, Germany., Lahti-Pulkkinen M; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Finnish Institute for Health and Welfare, Helsinki, Finland.; Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK., Cruceanu C; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden., Henrich W; Department of Obstetrics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, Berlin, Germany., Plagemann A; Department of Obstetrics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, Berlin, Germany.; Department of Experimental Obstetrics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, Berlin, Germany., Räikkönen K; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Department of Obstetrics and Gynecology, HUS Helsinki University Hospital, Helsinki, Finland., Braun T; Department of Obstetrics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, Berlin, Germany.; Department of Experimental Obstetrics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, Berlin, Germany., Binder EB; Department Genes and Environment, Max Planck Institute of Psychiatry, Munich, Germany.; Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, Atlanta, GA, USA., Lahti J; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Entringer S; Institute of Medical Psychology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, Berlin, Germany. sonja.entringer@charite.de.; Department of Pediatrics, Health and Disease Research Program, School of Medicine, University of California, Irvine, CA, USA. sonja.entringer@charite.de.
Jazyk: angličtina
Zdroj: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2024 Apr 10; Vol. 81 (1), pp. 177. Date of Electronic Publication: 2024 Apr 10.
DOI: 10.1007/s00018-024-05208-0
Abstrakt: Biological sex is a key variable influencing many physiological systems. Disease prevalence as well as treatment success can be modified by sex. Differences emerge already early in life and include pregnancy complications and adverse birth outcomes. The placenta is a critical organ for fetal development and shows sex-based differences in the expression of hormones and cytokines. Epigenetic regulation, such as DNA methylation (DNAm), may underlie the previously reported placental sexual dimorphism. We associated placental DNAm with fetal sex in three cohorts. Individual cohort results were meta-analyzed with random-effects modelling. CpG-sites differentially methylated with sex were further investigated regarding pathway enrichment, overlap with methylation quantitative trait loci (meQTLs), and hits from phenome-wide association studies (PheWAS). We evaluated the consistency of findings across tissues (CVS, i.e. chorionic villus sampling from early placenta, and cord blood) as well as with gene expression. We identified 10,320 epigenome-wide significant sex-differentially methylated probes (DMPs) spread throughout the epigenome of the placenta at birth. Most DMPs presented with lower DNAm levels in females. DMPs mapped to genes upregulated in brain, were enriched for neurodevelopmental pathways and significantly overlapped with meQTLs and PheWAS hits. Effect sizes were moderately correlated between CVS and placenta at birth, but only weakly correlated between birth placenta and cord blood. Sex differential gene expression in birth placenta was less pronounced and implicated genetic regions only marginally overlapped with those associated with differential DNAm. Our study provides an integrative perspective on sex-differential DNAm in perinatal tissues underscoring the possible link between placenta and brain.
(© 2024. The Author(s).)
Databáze: MEDLINE
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