Autism-like behaviors and abnormality of glucose metabolism in offspring derived from aging males with epigenetically modified sperm.
Autism-like behaviors and abnormality of glucose metabolism in offspring derived from aging males with epigenetically modified sperm.
复制标题
表观遗传修饰精子的老年男性后代的自闭症样行为和葡萄糖代谢异常
DOI：
10.18632/aging.104061
复制
发表时间：
2020-10-13
期刊：
影响因子：
--
通讯作者：
Sun F
中科院分区：
文献类型：
--
作者：
Zhao WL;Gu NH;Li ZZ;Wang GS;Cheng CY;Sun F
从人类流行病学研究和啮齿动物遗传模型中积累的证据表明，高龄雄性（阿帕）的后代易患代谢和神经系统疾病。然而，这些代谢和行为的变化，从阿帕在代际和跨代水平的分子机制（S）的知识是有限的。在这里，我们分别在12个月和18个月大的雄性小鼠的第一代和第二代中描述了葡萄糖和胆固醇代谢的变化，以及自闭症谱系障碍（ASD）样行为。阿帕小鼠精子的全基因组亚硫酸氢盐测序（WGBS）鉴定了全基因组内的差异甲基化区域（DMR）和启动子区域内的DMR，表明特定基因和相关通路可能与阿帕雄性后代的自闭症和异常葡萄糖代谢相关。这些结果强烈表明，男性精子老化诱导的表观遗传重编程可能导致高风险的异常葡萄糖代谢和ASD行为的发展，在代际和跨代的后代。
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.
登录
查看更多内容
影响因子：
16.6
作者：
Morimura N;Yasuda H;Yamaguchi K;Katayama KI;Hatayama M;Tomioka NH;Odagawa M;Kamiya A;Iwayama Y;Maekawa M;Nakamura K;Matsuzaki H;Tsujii M;Yamada K;Yoshikawa T;Aruga J
通讯作者：
Aruga J
影响因子：
10.6
作者：
Guastella, Adam J.;Einfeld, Stewart L.;Hickie, Ian B.
通讯作者：
Hickie, Ian B.
影响因子：
6
作者：
Carpentier, Pamela A.;Dingman, Andra L.;Palmer, Theo D.
通讯作者：
Palmer, Theo D.
影响因子：
64.8
作者：
Ng, Sheau-Fang;Lin, Ruby C. Y.;Morris, Margaret J.
通讯作者：
Morris, Margaret J.
影响因子：
12.3
作者：
Akalin A;Kormaksson M;Li S;Garrett-Bakelman FE;Figueroa ME;Melnick A;Mason CE
通讯作者：
Mason CE