Environmental factors can change phenotypes in exposed individuals and offspring and involve the germline, likely via biological signals in the periphery that communicate with germ cells. Here, using a mouse model of paternal exposure to traumatic stress, we identify circulating factors involving peroxisome proliferator‐activated receptor (PPAR) pathways in the effects of exposure to the germline. We show that exposure alters metabolic functions and pathways, particularly lipid‐derived metabolites, in exposed fathers and their offspring. We collected data in a human cohort exposed to childhood trauma and observed similar metabolic alterations in circulation, suggesting conserved effects. Chronic injection of serum from trauma‐exposed males into controls recapitulates metabolic phenotypes in the offspring. We identify lipid‐activated nuclear receptors PPARs as potential mediators of the effects from father to offspring. Pharmacological PPAR activation in vivo reproduces metabolic dysfunctions in the offspring and grand‐offspring of injected males and affects the sperm transcriptome in fathers and sons. In germ‐like cells in vitro, both serum and PPAR agonist induce PPAR activation. Together, these results highlight the role of circulating factors as potential communication vectors between the periphery and the germline.

中文翻译：

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循环因子参与通过种系传递父系经验


环境因素可以改变暴露个体和后代的表型，并涉及生殖细胞，可能是通过与生殖细胞通讯的外围生物信号。在这里，我们利用父亲遭受创伤性应激的小鼠模型，确定了涉及过氧化物酶体增殖物激活受体（PPAR）途径的循环因素对生殖系暴露影响的影响。我们发现，暴露会改变暴露的父亲及其后代的代谢功能和途径，特别是脂质衍生的代谢物。我们收集了遭受童年创伤的人类队列的数据，并观察到循环中类似的代谢变化，表明存在保守效应。将遭受创伤的雄性的血清长期注射到对照组中，可以重现后代的代谢表型。我们发现脂质激活核受体 PPAR 是父亲对后代影响的潜在介质。体内药理 PPAR 激活会在注射雄性的后代和孙代中重现代谢功能障碍，并影响父亲和儿子的精子转录组。在体外的类胚细胞中，血清和 PPAR 激动剂均可诱导 PPAR 激活。总之，这些结果强调了循环因子作为外周细胞和种系之间潜在通讯载体的作用。