Inhaltszusammenfassung

There is a growing body of evidence linking maternal overnutrition overnutrition to obesity and psychopathology that can be conserved across multiple generations. Recently Recently, we demonstrated in a maternal high-fat diet (HFD; MHFD) mouse model that MHFD induced enhanced enhanced hedonic behaviors and obesogenic phenotypes that were conserved across three generations via the paternal lineage, which was independent of sperm methylome changes. Here, we show that sperm sperm tRNA-derived sm...There is a growing body of evidence linking maternal overnutrition overnutrition to obesity and psychopathology that can be conserved across multiple generations. Recently Recently, we demonstrated in a maternal high-fat diet (HFD; MHFD) mouse model that MHFD induced enhanced enhanced hedonic behaviors and obesogenic phenotypes that were conserved across three generations via the paternal lineage, which was independent of sperm methylome changes. Here, we show that sperm sperm tRNA-derived small RNAs (tsRNAs) partly contribute to the transmission of such phenotypes. We observe observe increased expression of sperm tsRNAs in the F1 male offspring born to HFD-exposed dams. Microinjection Microinjection of sperm tsRNAs from the F1-HFD male into normal zygotes reproduces obesogenic phenotypes phenotypes and addictive-like behaviors, such as increased preference of palatable foods and enhanced enhanced sensitivity to drugs of abuse in the resultant offspring. The expression of several of the differentially differentially expressed sperm tsRNAs predicted targets such as CHRNA2 and GRIN3A, which have been implicated implicated in addiction pathology, are altered in the mesolimbic reward brain regions of the F1-HFD father father and the resultant HFD-tsRNA offspring. Together, our findings demonstrate that sperm tsRNA is is a potential vector that contributes to the transmission of MHFD-induced addictive-like behaviors and obesogenic phenotypes across generations, thereby emphasizing its role in diverse pathological outcomes outcomes.» weiterlesen» einklappen

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Klassifikation

DDC Sachgruppe:
Biowissenschaften, Biologie