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Science. 2016 Jan 22;351(6271):397-400. doi: 10.1126/science.aad7977. Epub 2015 Dec 31.

Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder.

Author information

1
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno, NV 89512 USA.
2
Key Laboratory of Nutrition and Metabolism, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
3
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. University of Chinese Academy of Sciences, Beijing 100049, China.
4
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
5
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. Beijing Royal Integrative Medicine Hospital, Beijing University of Chinese Medicine, Beijing, China.

Abstract

Increasing evidence indicates that metabolic disorders in offspring can result from the father's diet, but the mechanism remains unclear. In a paternal mouse model given a high-fat diet (HFD), we showed that a subset of sperm transfer RNA-derived small RNAs (tsRNAs), mainly from 5' transfer RNA halves and ranging in size from 30 to 34 nucleotides, exhibited changes in expression profiles and RNA modifications. Injection of sperm tsRNA fractions from HFD males into normal zygotes generated metabolic disorders in the F1 offspring and altered gene expression of metabolic pathways in early embryos and islets of F1 offspring, which was unrelated to DNA methylation at CpG-enriched regions. Hence, sperm tsRNAs represent a paternal epigenetic factor that may mediate intergenerational inheritance of diet-induced metabolic disorders.

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PMID:
26721680
DOI:
10.1126/science.aad7977
[Indexed for MEDLINE]
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