Maternal overnutrition programs hedonic and metabolic phenotypes across generations through sperm tsRNAs

There is a growing body of evidence linking maternal overnutri-tion to obesity and psychopathology that can be conserved acrossmultiple generations. Recently, we demonstrated in a maternalhigh-fat diet (HFD; MHFD) mouse model that MHFD inducedenhanced hedonic behaviors and obesogenic phenotypes thatwere conserved across three generations via the paternal lineage,which was independent of sperm methylome changes. Here, weshow that sperm tRNA-derived small RNAs (tsRNAs) partly contrib-ute to the transmission of such phenotypes. We observe increasedexpression of sperm tsRNAs in the F1 male offspring born to HFD-exposed dams. Microinjection of sperm tsRNAs from the F1-HFDmale into normal zygotes…