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• Research Paper Volume 12, Issue 19 pp 19766-19784

  Autism-like behaviors and abnormality of glucose metabolism in offspring derived from aging males with epigenetically modified sperm

  Relevance score: 12.850445

  Wen-Long Zhao, Ni-Hao Gu, Zheng-Zheng Li, Gui-Shuan Wang, C. Yan Cheng, Fei Sun

  Keywords: advanced paternal age, glucose metabolism, autism-like behavior, intergenerational and transgenerational offspring, DNA methylation

  Published in Aging on October 13, 2020

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  Accumulating evidence from epidemiological studies of humans and genetic models in rodents has shown that offspring from males of advanced paternal age (APA) are susceptible to metabolic and neurological disorders. However, knowledge of molecular mechanism(s) underlying these metabolic and behavioral changes at the intergeneration and trans-generation levels from APA is limited. Here, we characterized changes on glucose and cholesterol metabolism, and also autism spectrum disorders (ASD)-like behaviors in 1^st and 2^nd generations from 12- and 18-month-old male mice, respectively. Whole Genome Bisulfite Sequencing (WGBS) of sperm from APA mice identified differentially methylated regions (DMRs) within the whole genome, and DMRs within promoter regions, suggesting that specific genes and relevant pathways might be associated with autism and aberrant glucose metabolism in the offspring from APA males. These results strongly suggest that epigenetic reprogramming induced by aging in male sperm may lead to high risks of aberrant glucose metabolism and the development of ASD behaviors in intergenerational and transgenerational offspring.