Sperm RNA Contributes to Intergenerational Inheritance of Acquired Metabolic Disorder

Increasing evidence indicates that metabolic diseases such as obesity caused by a high-fat diet can be "memorized" in sperm and passed on to the next generation, resulting in obesity in offspring.

This homotropic inheritance mechanism mediated by sperm involves the storage and transmission of epigenetic information other than DNA sequences in sperm, and deciphering such epigenetic information is a major challenge in the field. 

Using a high-fat diet mouse model, a joint research team led by ZHOU Qi and DUAN Enkui from the Institute of Zoology and ZHAI Qiwei from the Shanghai Institute of Nutrition and Health has found that a subset of sperm small RNAs, named 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 after paternal high-fat diet.

Injection of sperm tsRNA fractions from high-fat diet 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, indicating sperm tsRNAs can transmit paternal high-fat diet information into next generation 

This study for the first time presents the ability of sperm tsRNAs, which acts as a new paternal epigenetic factor that may mediate intergenerational inheritance of diet-induced metabolic disorders. 

This study provides a new avenue to studying the intergenerational inheritance of acquired traits from the aspect of sperm RNA. It proposes that sperm tsRNAs are a new class of paternal epigenetic factors that can mediate the transgenerational transmission of acquired metabolic disorders. 

The study was published in Science.

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