Exposure to childhood maltreatment is associated with specific epigenetic patterns in sperm

: Tuulari, Jetro J.; Bourgery, Matthieu; Iversen, Jo; Koefoed, Thomas Gade; Ahonen, Annukka; Ahmedani, Ammar; Kataja, Eeva-Leena; Karlsson, Linnea; Barrès, Romain; Karlsson, Hasse; Kotaja, Noora

Publisher: Springer Nature

: 2025

: Molecular Psychiatry

: 1359-4184

: 1476-5578

DOI: https://doi.org/10.1038/s41380-024-02872-3

: https://doi.org/10.1038/s41380-024-02872-3

: https://research.utu.fi/converis/portal/detail/Publication/484762432

Childhood maltreatment exposure (CME) increases the risk of adverse long-term health consequences for the exposed individual. Animal studies suggest that CME may also influence the health and behaviour in the next generation offspring through CME-driven epigenetic changes in the germ line. Here we investigated the associated between early life stress on the epigenome of sperm in humans with history of CME. We measured paternal CME using the Trauma and Distress Scale (TADS) questionnaire and mapped sperm-borne sncRNAs expression by small RNA sequencing (small RNA-seq) and DNA methylation (DNAme) in spermatozoa by reduced-representation bisulfite sequencing (RRBS-seq) in males from the FinnBrain Birth Cohort Study. The study design was a (nested) case-control study, high-TADS (TADS ≥ 39, n = 25 for DNAme and n = 14 for small RNA-seq) and low-TADS (TADS ≤ 10, n = 30 for DNAme and n = 16 for small RNA-seq). We identified 3 genomic regions with differential methylation between low and high-TADS and 68 tRNA-derived small RNAs (tsRNAs) and miRNAs with different levels in males with high CME (False discovery rate, FDR corrected p < 0.05). Of potential interest, we identified differential expression of miRNA hsa-mir-34c-5p and differential methylation levels near the CRTC1 and GBX2 genes, which are documented to control brain development. Our results provide further evidence that early life stress influences the paternal germline epigenome and supports a possible effect in modulating the development of the central nervous system of the next generation.

s41380-024-02872-3.pdf

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Jetro J. Tuulari was supported by the State Research Grant (ERVA), Sigrid Juselius Foundation, Finnish Medical Foundation, Signe ja Ane Gyllenberg Foundation, and Emil Aaltonen Foundation. Linnea Karlsson was supported by the Academy of Finland (#325292). Romain Barres and Jo Iversen were supported by a Challenge Programme Grant from the Novo Nordisk Foundation (NNF18OC0033754) to the Gametic Epigenetics Consortium against Obesity (GECKO). The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research center at the University of Copenhagen, partially funded by an unrestricted donation from the Novo Nordisk Foundation (NNF18CC0034900). This work was supported by the French Government (National Research Agency, ANR) through the “Investments for the Future” programmes LABEX SIGNALIFE ANR-11-LABX-0028-01 and IDEX UCAJedi ANR-15-IDEX-01. Thomas Gade Koefoed and the Single-Cell Omics Plaform is funded by the Novo Nordisk Foundation. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research center at the University of Copenhagen, partially funded by an unrestricted donation from the Novo Nordisk Foundation (NNF18CC0034900). Eeva-Leena Kataja was funded by Signe ja Ane Gyllenberg Foundation, Turku University Foundation, Academy of Finland (308252). Noora Kotaja was supported by Academy of Finland, Sigrid Jusélius Foundation, Novo Nordisk Foundation, Jalmari and Rauha Ahokas Foundation, and Jane and Atos Erkko Foundation. Open Access funding provided by University of Turku (including Turku University Central Hospital).