GSE174504
Oocyte piRNAs mediate intergenerational transmission of an acquired metabolic disorder (small RNA sequencing)
Traditional research has focused on DNA as the molecule that carries heritable information from the parent to the offspring. However, increasing evidence suggests that information beyond the DNA sequence, termed epigenetic information, can also transmit certain information from one generation to the next. Whereas paternal epigenetic germline inheritance has been well elucidated, as the father contributes little more than a sperm cell to the offspring, maternal epigenetic inheritance via gametes remains largely unclear. Here, using an in vitro fertilization system and a micromanipulation strategy, we demonstrate that oocyte piRNAs mediate intergenerational transmission of an acquired metabolic disorder. Changes in the expression profiles of many oocyte piRNAs are observed in a maternal chronic high-fat diet (HFD) mouse model. Injection of the oocyte piRNAs from HFD females into normal zygotes resulted in impaired glucose tolerance and decreased insulin sensitivity in the F1 offspring. A series of genes involved in glucose metabolism and the insulin signaling pathway were differentially expressed in the pancreatic islets of the F1 offspring. Bisulfite genome sequencing of the islets of the F1 offspring revealed changes in cytosine methylation that correlated with the observed gene expression patterns. These data identified oocyte piRNAs as novel carriers of epigenetic information and highlight the importance of long-term maternal health before conception. Overall design: Examination of the effect of maternal high-fat diet on the oocyte small-RNA expression profiles.