Unknown

Dataset Information

0

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


ABSTRACT: There is a growing body of evidence linking maternal overnutrition to obesity and psychopathology that can be conserved across multiple generations. Recently, we demonstrated in a maternal high-fat diet (HFD; MHFD) mouse model that MHFD induced 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 tRNA-derived small RNAs (tsRNAs) partly contribute to the transmission of such phenotypes. We observe increased expression of sperm tsRNAs in the F1 male offspring born to HFD-exposed dams. Microinjection of sperm tsRNAs from the F1-HFD male into normal zygotes reproduces obesogenic phenotypes and addictive-like behaviors, such as increased preference of palatable foods and enhanced sensitivity to drugs of abuse in the resultant offspring. The expression of several of the differentially expressed sperm tsRNAs predicted targets such as CHRNA2 and GRIN3A, which have been implicated in addiction pathology, are altered in the mesolimbic reward brain regions of the F1-HFD father and the resultant HFD-tsRNA offspring. Together, our findings demonstrate that sperm tsRNA 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.

SUBMITTER: Sarker G 

PROVIDER: S-EPMC6534971 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Sarker Gitalee G   Sun Wenfei W   Rosenkranz David D   Pelczar Pawel P   Opitz Lennart L   Efthymiou Vissarion V   Wolfrum Christian C   Peleg-Raibstein Daria D  

Proceedings of the National Academy of Sciences of the United States of America 20190506 21


There is a growing body of evidence linking maternal overnutrition to obesity and psychopathology that can be conserved across multiple generations. Recently, we demonstrated in a maternal high-fat diet (HFD; MHFD) mouse model that MHFD induced 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 tRNA-derived small RNAs (tsRNAs) partly contribute to th  ...[more]

Similar Datasets

| S-EPMC6185972 | biostudies-literature
| S-EPMC8630171 | biostudies-literature
| S-EPMC4957639 | biostudies-literature
2015-12-31 | E-GEOD-75544 | biostudies-arrayexpress
2015-12-31 | GSE75544 | GEO
| S-EPMC7235386 | biostudies-literature
| S-EPMC6113193 | biostudies-literature
| S-EPMC3696570 | biostudies-other
| S-EPMC8441364 | biostudies-literature
| S-EPMC9205528 | biostudies-literature