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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

Wen-Long Zhao1,2,3, Ni-Hao Gu1,2,3, Zheng-Zheng Li1,2,3, Gui-Shuan Wang4, C. Yan Cheng5, Fei Sun1,2,3,4
  • 1The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  • 2Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
  • 3Shanghai Municipal Key Clinical Speciality, Shanghai, China
  • 4Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, Jiangsu, China
  • 5The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, NY 10065, USA
* Equal contribution
Received: June 29, 2020Accepted: August 31, 2020Published: October 13, 2020
https://doi.org/10.18632/aging.104061

Copyright: © 2020 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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 1st and 2nd 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.