Key Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
MOE Joint International Research Laboratory of Animal Health & Food Safety, Nanjing Agricultural University, Nanjing 210095, China.
Oxid Med Cell Longev. 2022 Jun 6;2022:6877283. doi: 10.1155/2022/6877283. eCollection 2022.
There is growing evidence that paternal environmental information alters small noncoding RNAs (sncRNAs) in sperm and in turn can induce alterations of metabolic and behavioral phenotypes of the next generation. However, the potential mediators of the effects remain to be elucidated. A great diversity of environmental insults and stresses can convergently induce the elevation of reactive oxygen species (ROS) in sperm; nonetheless, it remains unclear whether ROS mediates the biogenesis of sncRNAs in sperm and participates in the reprogramming of offspring phenotypes. Here, we show that ROS could induce the alteration of sncRNA profiles in sperm, especially for transfer RNA-derived small RNAs (tsRNAs) and ribosomal RNA-derived small RNAs (rsRNAs). Zygotic injection of 29-34 nt RNA fractions (predominantly tsRNAs and rsRNAs) from oxidative stress (OS) sperm could induce depressive-like and anxiety-like behaviors in male offspring. Moreover, zygotic injection with synthetic RNAs partially resembled OS sperm-induced depressive-like and anxiety-like behaviors in offspring. Male offspring maintained on a chow diet was found to develop impaired glucose tolerance and hyperactive hepatic gluconeogenesis, accompanied by the upregulation of hepatic gluconeogenic and lipolytic genes. Together, our results have shown that ROS-induced alteration of sncRNA profiles in sperm contributes to the alterations of behavioral and metabolic phenotypes of the offspring.
越来越多的证据表明，父系环境信息会改变精子中的小非编码 RNA（sncRNA），进而可以诱导下一代代谢和行为表型的改变。然而，潜在的介导物仍有待阐明。各种环境刺激和应激都可以趋同地诱导精子中活性氧（ROS）的升高；尽管如此，ROS 是否介导精子中 sncRNA 的生物发生并参与后代表型的重编程仍不清楚。在这里，我们表明 ROS 可以诱导精子中 sncRNA 谱的改变，特别是转移 RNA 衍生的小 RNA（tsRNA）和核糖体 RNA 衍生的小 RNA（rsRNA）。来自氧化应激（OS）精子的 29-34nt RNA 片段（主要是 tsRNA 和 rsRNA）的受精卵注射可以诱导雄性后代出现抑郁样和焦虑样行为。此外，与 OS 精子诱导的雄性后代的抑郁样和焦虑样行为相似，用合成 RNA 进行受精卵注射也可以部分诱导这些行为。研究发现，维持在标准饮食上的雄性后代会出现葡萄糖耐量受损和肝糖异生过度活跃的情况，并伴有肝糖异生和脂肪分解基因的上调。总之，我们的研究结果表明，ROS 诱导的精子中 sncRNA 谱的改变导致了后代行为和代谢表型的改变。
