Recent work has shown that maternal obesity in mice is associated with physiological and behavioral changes that affect up to three generations of offspring.
The researchers found that levels of certain small molecules in sperm called tRNA-derived small RNAs (tsRNAs) were significantly higher in the sperm of males born to mothers fed a high-fat diet (HFD), compared to males from mothers fed a normal diet.
The authors extracted sperm tsRNA from the offspring of HFD-fed and normal diet-fed mothers and injected it into normal mouse zygotes to generate HFD-tsRNA and control offspring, respectively. Compared with controls, offspring born through the HFD-tsRNA injection exhibited increased addictive-like behaviors, such as an increased preference for and consumption of HFD, sucrose, and alcohol, and enhanced sensitivity to amphetamines.
Additionally, HFD-tsRNA offspring developed obesity and impaired insulin sensitivity compared with controls, especially when given free access to HFD and sucrose. HFD-tsRNAs targeted several key genes involved in addiction and obesity, and both the HFD sperm donors and HFD-tsRNA offspring showed altered 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.
According to the authors, the results suggest that sperm tsRNAs contribute to the transgenerational transmission of addictive and obesity-causing traits induced by maternal HFD.
Maternal obesity passed on addictive -like behaviors through generations via RNA
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