Altered sperm tsRNAs in aged male contribute to anxiety-like behavior in offspring,Aging Cell

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Altered sperm tsRNAs in aged male contribute to anxiety-like behavior in offspring
Aging Cell ( IF 8.0 ) Pub Date : 2021-08-27 , DOI: 10.1111/acel.13466
Yi Guo _{1,

2} , Dandan Bai ₂ , Wenqiang Liu ₂ , Yingdong Liu ₂ , Yalin Zhang ₂ , Xiaochen Kou ₂ , Jiayu Chen ₂ , Hong Wang ₂ , Xiaoming Teng ₂ , Ji Zuo ₁ , Shaorong Gao ₂

Affiliation

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.

中文翻译：

老年男性精子 tsRNA 的改变导致后代出现焦虑样行为

世界范围内首次怀孕的父母年龄正在增加。年迈父亲的后代与精神分裂症和自闭症等几种神经精神疾病的风险较高有关，但其潜在机制仍然难以捉摸。在这里，我们报告说，小鼠父亲的高龄改变了转移 RNA 衍生的小 RNA (tsRNA) 的分布。将老年雄性小鼠的精子 tsRNA 注射到受精卵中会导致 F1 雄性小鼠出现焦虑样行为。这些 F1 雄性小鼠大脑皮层和海马的 RNA 测序改变了多巴胺能突触和神经营养因子的基因表达。来自老年雄性小鼠注射的 tsRNAs 也改变了双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，精子 tsRNA 谱在人类衰老过程中发生了显着变化。上调的精子 tsRNA 靶基因参与神经发生和神经系统发育。这些结果表明，与衰老相关的精子 tsRNA 变化可能有助于行为特征的代际传递。

更新日期：2021-09-15

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