Altered sperm tsRNAs in aged male contribute to anxiety-like behavior in offspring.
Altered sperm tsRNAs in aged male contribute to anxiety-like behavior in offspring.
复制标题
老年男性精子 tsRNA 的改变导致后代出现焦虑样行为
作者：
Guo Y;Bai D;Liu W;Liu Y;Zhang Y;Kou X;Chen J;Wang H;Teng X;Zuo J;Gao S
在世界范围内，首次怀孕的父母年龄正在增加。父亲年迈的子女患精神分裂症和自闭症等神经精神疾病的风险较高，但其潜在机制仍不清楚。在这里，我们报告了小鼠的高父年龄改变了转移RNA衍生的小RNA(TsRNAs)的特征。将老年雄性小鼠的精子tsRNAs注射到受精卵中，可诱导F1雄性小鼠出现类似焦虑的行为。对F1雄性小鼠大脑皮层和海马区的RNA测序改变了多巴胺能突触和神经营养素的基因表达。老年雄性小鼠注射的tsRNA也改变了两细胞和囊胚期胚胎中神经精神病学相关基因的表达。更重要的是，在人类衰老过程中，精子tsRNA图谱发生了显著变化。上调的精子tsRNA靶基因参与了神经发生和神经系统发育。这些结果表明，精子tsRNA的增龄相关变化可能有助于行为特征的代际传递。在小鼠和人类中，父亲的高龄改变了转移RNA衍生的小RNA(TsRNAs)的特征。将老年雄性小鼠的精子tsRNA注射到受精卵中，在F1雄性小鼠中诱导了类似焦虑的行为，并改变了双细胞和囊胚中神经精神病学相关基因的表达。这些结果表明，精子tsRNA的增龄相关变化可能有助于行为特征的代际传递。
Parental age at first pregnancy is increasing worldwide. The offspring of aged father has been associated with higher risk of several neuropsychiatric disorders, such as schizophrenia and autism, but the underlying mechanism remains elusive. Here we report that advanced paternal age in mice alters the profile of transfer RNA‐derived small RNAs (tsRNAs). Injection of sperm tsRNAs from aged male mice into zygotes induced anxiety‐like behaviors in F1 males. RNA sequencing of the cerebral cortex and hippocampus of those F1 male mice altered the gene expression of dopaminergic synapse and neurotrophin. tsRNAs from aged male mice injection also altered the neuropsychiatry‐related gene expression in two‐cell and blastocyst stage embryos. More importantly, the sperm tsRNA profile changes significantly during aging in human. The up‐regulated sperm tsRNA target genes were involved in neurogenesis and nervous system development. These results suggest that aging‐related changes of sperm tsRNA may contribute to the intergenerational transmission of behavioral traits. Advanced paternal age in mice and human alters the profile of transfer RNA‐derived small RNAs (tsRNAs). Injection of sperm tsRNA from aged male mice into zygotes induced anxiety‐like behaviors in F1 males and also altered the neuropsychiatry‐related gene expression in two‐cell and blastocyst embryos. These results suggest that aging‐related changes of sperm tsRNA may contribute to the intergenerational transmission of behavioral traits.
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