Ancestral vinclozolin exposure alters the epigenetic transgenerational inheritance of sperm small noncoding RNAs

被引:41
作者
Schuster, Andrew [1 ]
Skinner, Michael K. [2 ]
Yan, Wei [1 ]
机构
[1] Univ Nevada, Dept Physiol & Cell Biol, Reno, NV 89557 USA
[2] Washington State Univ, Sch Biol Sci, Ctr Reprod Biol, Pullman, WA 99164 USA
基金
美国国家科学基金会;
关键词
transgenerational; noncoding RNA; sperm; vinclozolin; epigenetic inheritance;
D O I
10.1093/eep/dvw001
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Exposure to the agricultural fungicide vinclozolin during gestation promotes a higher incidence of various diseases in the subsequent unexposed F3 and F4 generations. This phenomenon is termed epigenetic transgenerational inheritance and has been shown to in part involve alterations in DNA methylation, but the role of other epigenetic mechanisms remains unknown. The current study investigated the alterations in small noncoding RNA (sncRNA) in the sperm from F3 generation control and vinclozolin lineage rats. Over 200 differentially expressed sncRNAs were identified and the tRNA-derived sncRNAs, namely 5' halves of mature tRNAs (5' halves), displayed the most dramatic changes. Gene targets of the altered miRNAs and tRNA 5' halves revealed associations between the altered sncRNAs and differentially DNA methylated regions. Dysregulated sncRNAs appear to correlate with mRNA profiles associated with the previously observed vinclozolin-induced disease phenotypes. Data suggest potential connections between sperm-borne RNAs and the vinclozolin-induced epigenetic transgenerational inheritance phenomenon.
引用
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页数:10
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