Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder
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Increasing evidences indicate diet-induced metabolic disorder could be paternally inherited, but the exact sperm epigenetic carrier remains unclear. Here, in a paternal high-fat diet (HFD) mouse model, we revealed that a highly enriched subset of sperm small RNAs (30-34 nt) that derived from the 5â halves of tRNAs (tsRNAs), exhibit changes in both expression profiles and RNA modifications. Injection of sperm tsRNAs from HFD male but not synthetic tsRNAs lacking RNA modifications, into normal zygotes generated metabolic disorders in the F1 offspring. Injection of HFD sperm tsRNAs derails gene expression in both early embryos and islets of F1 offspring, enriched in metabolic pathways, but unrelated to DNA methylation at CpG-enriched region. Collectively, we uncover sperm tsRNAs as a type of âepigenetic carrierâ that mediate intergenerational inheritance of acquired traits.
