Authors: Yanwen Zhang, Li Ren, Xiaoxiao Sun, Zhilong Zhang, Jie Liu, Yining Xin, Jianmin Yu, Yimin Jia, Jinghao Sheng, Guo-fu Hu, Ruqian Zhao, Bin He
Published: 2021-11-29
DOI: 10.1038/s41467-021-26909-1
Source: Full article
AbstractPaternal environmental inputs can influence various phenotypes in offspring, presenting tremendous implications for basic biology and public health and policy. However, which signals function as a nexus to transmit paternal environmental inputs to offspring remains unclear. Here we show that offspring of fathers with inflammation exhibit metabolic disorders including glucose intolerance and obesity. Deletion of a mouse tRNA RNase, Angiogenin (Ang), abolished paternal inflammation-induced metabolic disorders in offspring. Additionally,Angdeletion prevented the inflammation-induced alteration of 5′-tRNA-derived small RNAs (5′-tsRNAs) expression profile in sperm, which might be essential in composing a sperm RNA ‘coding signature’ that is needed for paternal epigenetic memory. Microinjection of sperm 30–40 nt RNA fractions (predominantly 5′-tsRNAs) from inflammatoryAng+/+males but notAng–/–males resulted in metabolic disorders in the resultant offspring. Moreover, zygotic injection with synthetic 5′-tsRNAs which increased in inflammatory mouse sperm and decreased byAngdeletion partially resembled paternal inflammation-induced metabolic disorders in offspring. Together, our findings demonstrate that Ang-mediated biogenesis of 5′-tsRNAs in sperm contributes to paternal inflammation-induced metabolic disorders in offspring.