Epigenetic transgenerational inheritance of toxicant exposure-specific non-coding RNA in sperm.

IF 4.8 Q1 GENETICS & HEREDITY Environmental Epigenetics Pub Date : 2024-09-04 eCollection Date: 2024-01-01 DOI:10.1093/eep/dvae014
Hayden McSwiggin, Rubens Magalhães, Eric E Nilsson, Wei Yan, Michael K Skinner
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Abstract

Environmentally induced epigenetic transgenerational inheritance of phenotypic variation and disease susceptibility requires the germ cell (sperm or egg) transmission of integrated epigenetic mechanisms involving DNA methylation, histone modifications, and non-coding RNA (ncRNA) actions. Previous studies have demonstrated that transgenerational exposure and disease-specific differential DNA methylation regions (DMRs) in sperm are observed and that ncRNA-mediated DNA methylation occurs. The current study was designed to determine if transgenerational exposure-specific ncRNAs exist in sperm. Specifically, toxicants with distinct mechanisms of action including the fungicide vinclozolin (anti-androgenic), pesticide dichlorodiphenyltrichloroethane (estrogenic), herbicide atrazine (endocrine disruptor at cyclic adenosine monophosphate level), and hydrocarbon mixture jet fuel (JP8) (aryl hydrocarbon receptor disruptor) were used to promote transgenerational disease phenotypes in F3 generation outbred rats. New aliquots of sperm, previously collected and used for DNA methylation analyses, were used in the current study for ncRNA sequencing analyses of nuclear RNA. Significant changes in transgenerational sperm ncRNA were observed for each transgenerational exposure lineage. The majority of ncRNA was small noncoding RNAs including piwi-interacting RNA, tRNA-derived small RNAs, microRNAs, rRNA-derived small RNA, as well as long ncRNAs. Although there was some overlap among the different classes of ncRNA across the different exposures, the majority of differentially expressed ncRNAs were exposure-specific with no overlapping ncRNA between the four different exposure lineages in the transgenerational F3 generation sperm nuclear ncRNAs. The ncRNA chromosomal locations and gene associations were identified for a small number of differential expressed ncRNA. Interestingly, an overlap analysis between the transgenerational sperm DMRs and ncRNA chromosomal locations demonstrated small populations of overlapping ncRNA, but a large population of non-overlapping ncRNAs. Observations suggest that transgenerational sperm ncRNAs have both exposure-specific populations within the different classes of ncRNA, as well as some common populations of ncRNAs among the different exposures. The lack of co-localization of many of the ncRNAs with previously identified transgenerational DMRs suggests a distal integration of the different epigenetic mechanisms. The potential use of ncRNA analyses for transgenerational toxicant exposure assessment appears feasible.

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精子中毒物暴露特异性非编码 RNA 的表观遗传跨代遗传。
环境诱导的表型变异和疾病易感性的表观遗传转代需要生殖细胞(精子或卵子)传递涉及 DNA 甲基化、组蛋白修饰和非编码 RNA(ncRNA)作用的综合表观遗传机制。以前的研究表明,精子中存在跨代暴露和疾病特异性差异DNA甲基化区域(DMR),并且存在ncRNA介导的DNA甲基化。目前的研究旨在确定精子中是否存在跨代暴露特异性 ncRNA。具体来说,研究人员使用了具有不同作用机制的毒物,包括杀真菌剂长春唑啉(抗雄激素)、杀虫剂二氯二苯基三氯乙烷(雌激素)、除草剂阿特拉津(环磷酸腺苷水平的内分泌干扰物)和碳氢化合物混合物喷气燃料(JP8)(芳基烃受体干扰物),以促进 F3 代近交系大鼠出现跨代疾病表型。在本研究中,先前收集并用于 DNA 甲基化分析的新精子等分样品被用于核 RNA 的 ncRNA 测序分析。在每个转代暴露品系中都观察到了转代精子 ncRNA 的显著变化。大部分 ncRNA 是小型非编码 RNA,包括 piwi-interacting RNA、tRNA 衍生的小型 RNA、microRNA、rRNA 衍生的小型 RNA 以及长 ncRNA。虽然不同暴露中不同类别的 ncRNA 有一些重叠,但大多数差异表达的 ncRNA 是特定暴露的,在转代 F3 代精子核 ncRNA 中,四个不同暴露系之间没有重叠的 ncRNA。少数差异表达的 ncRNA 的染色体位置和基因关联已经确定。有趣的是,转代精子 DMRs 与 ncRNA 染色体位置之间的重叠分析表明,重叠 ncRNA 的数量很少,但非重叠 ncRNA 的数量却很大。观察结果表明,在不同类别的 ncRNA 中,跨代精子 ncRNA 既有暴露特异性群体,也有不同暴露中的一些共同 ncRNA 群体。许多 ncRNA 与先前确定的跨代 DMRs 没有共定位,这表明不同的表观遗传机制是远距离整合的。将 ncRNA 分析用于跨代毒物暴露评估似乎是可行的。
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来源期刊
Environmental Epigenetics
Environmental Epigenetics GENETICS & HEREDITY-
CiteScore
6.50
自引率
5.30%
发文量
0
审稿时长
17 weeks
期刊最新文献
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