Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, 686 North Pleasant Street, Amherst, MA 01003, USA.
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskye Gory, House 1, Building 40, 119992 Moscow, Russia.
Int J Mol Sci. 2020 Nov 4;21(21):8252. doi: 10.3390/ijms21218252.
Advanced paternal age at fertilization is a risk factor for multiple disorders in offspring and may be linked to age-related epigenetic changes in the father's sperm. An understanding of aging-related epigenetic changes in sperm and environmental factors that modify such changes is needed. Here, we characterize changes in sperm small non-coding RNA (sncRNA) between young pubertal and mature rats. We also analyze the modification of these changes by exposure to environmental xenobiotic 2,2',4,4'-tetrabromodiphenyl ether (BDE-47). sncRNA libraries prepared from epididymal spermatozoa were sequenced and analyzed using DESeq 2. The distribution of small RNA fractions changed with age, with fractions mapping to rRNA and lncRNA decreasing and fractions mapping to tRNA and miRNA increasing. In total, 249 miRNA, 908 piRNA and 227 tRNA-derived RNA were differentially expressed (twofold change, false discovery rate (FDR) ≤ 0.05) between age groups in control animals. Differentially expressed miRNA and piRNA were enriched for protein-coding targets involved in development and metabolism, while piRNA were enriched for long terminal repeat (LTR) targets. BDE-47 accelerated age-dependent changes in sncRNA in younger animals, decelerated these changes in older animals and increased the variance in expression of all sncRNA. Our results indicate that the natural aging process has profound effects on sperm sncRNA profiles and this effect may be modified by environmental exposure.
受精时的高龄父亲是后代多种疾病的风险因素，可能与父亲精子中与年龄相关的表观遗传变化有关。需要了解精子中与年龄相关的表观遗传变化以及改变这些变化的环境因素。在这里，我们描述了年轻青春期和成熟大鼠精子中小非编码 RNA（sncRNA）之间的变化。我们还分析了暴露于环境异生物质 2,2',4,4'-四溴二苯醚（BDE-47）对这些变化的修饰。从小鼠附睾精子中制备 sncRNA 文库，并使用 DESeq 2 对文库进行测序和分析。小 RNA 分数的分布随年龄而变化，与 rRNA 和 lncRNA 映射的分数减少，与 tRNA 和 miRNA 映射的分数增加。在对照组动物中，249 个 miRNA、908 个 piRNA 和 227 个 tRNA 衍生的 RNA 在不同年龄组之间差异表达（两倍变化，错误发现率（FDR）≤0.05）。差异表达的 miRNA 和 piRNA 富含参与发育和代谢的蛋白质编码靶标，而 piRNA 富含长末端重复（LTR）靶标。BDE-47 加速了年轻动物中 sncRNA 的年龄依赖性变化，减缓了老年动物中的这些变化，并增加了所有 sncRNA 表达的方差。我们的结果表明，自然衰老过程对精子 sncRNA 谱有深远影响，这种影响可能会被环境暴露所改变。
