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
FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Department of Clinical Medicine, University of Turku, Turku, Finland.
Department of Psychiatry, Turku University Hospital and University of Turku, Turku, Finland.
Mol Psychiatry. 2025 Jun;30(6):2635-2644. doi: 10.1038/s41380-024-02872-3. Epub 2025 Jan 3.
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.
童年期受虐待经历（CME）会增加受影响个体出现长期不良健康后果的风险。动物研究表明，CME还可能通过CME驱动的种系表观遗传变化影响下一代后代的健康和行为。在此，我们调查了有CME病史的人类精子表观基因组与早期生活压力之间的关联。我们使用创伤与痛苦量表（TADS）问卷测量父亲的CME，并通过小RNA测序（small RNA-seq）绘制精子携带的sncRNAs表达图谱，通过简化代表性亚硫酸氢盐测序（RRBS-seq）对来自芬兰脑出生队列研究的男性精子中的DNA甲基化（DNAme）进行分析。研究设计为（嵌套）病例对照研究，高TADS组（TADS≥39，DNAme分析n = 25，小RNA-seq分析n = 14）和低TADS组（TADS≤10，DNAme分析n = 30，小RNA-seq分析n = 16）。我们在低TADS组和高TADS组之间鉴定出3个甲基化差异的基因组区域，以及68个在高CME男性中表达水平不同的tRNA衍生小RNA（tsRNAs）和miRNA（错误发现率，FDR校正p < 0.05）。值得关注的是，我们鉴定出miRNA hsa-mir-34c-5p的差异表达以及CRTC1和GBX2基因附近的甲基化差异水平，这些基因已被证明对大脑发育起控制作用。我们的结果提供了进一步的证据，表明早期生活压力会影响父系种系表观基因组，并支持其可能对调节下一代中枢神经系统发育产生影响。
