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Epigenome-wide association study for transgenerational disease sperm epimutation biomarkers following ancestral exposure to jet fuel hydrocarbons.
Reproductive Toxicology ( IF 3.3 ) Pub Date : 2020-09-06 , DOI: 10.1016/j.reprotox.2020.08.010
Millissia Ben Maamar 1 , Eric Nilsson 1 , Jennifer L M Thorson 1 , Daniel Beck 1 , Michael K Skinner 1
Affiliation  

Jet fuel hydrocarbons is the generic name for aviation fuels used in gas-turbine engine powered aircraft. The Deepwater Horizon oil rig explosion created the largest environmental disaster in U.S. history, and the second largest oil spill in human history with over 800 million liters of hydrocarbons released into the Gulf of Mexico over a period of 3 months. Due to the widespread use of jet fuel hydrocarbons, this compound mixture has been recognized as the single largest chemical exposure for military personnel. Previous animal studies have demonstrated the ability of jet fuel (JP-8) exposure to promote the epigenetic transgenerational inheritance of disease susceptibility in subsequent generations. The diseases observed include late puberty, kidney, obesity and multiple disease pathologies. The current study is distinct and was designed to identify potential sperm DNA methylation biomarkers for specific transgenerational diseases. Observations show disease specific differential DNA methylation regions (DMRs) called epimutations in the transgenerational F3 generation great-grand-offspring male rats ancestrally exposed to jet fuel. The potential epigenetic DMR biomarkers were identified for late puberty, kidney, obesity, and multiple diseases, and found to be predominantly disease specific. These disease specific DMRs have associated genes that were previously shown to be linked with each of these specific diseases. Therefore, the germline (i.e. sperm) has environmentally induced ancestrally derived epimutations that have the potential to transgenerationally transmit disease susceptibilities to subsequent generations. Epigenetic biomarkers for specific diseases could be developed as medical diagnostics to facilitate clinical management of disease, and allow preventative medicine therapeutics.



中文翻译:


祖先接触喷气燃料碳氢化合物后跨代疾病精子表突变生物标志物的表观基因组关联研究。



喷气燃料碳氢化合物是用于燃气涡轮发动机驱动的飞机的航空燃料的通用名称。深水地平线石油钻井平台爆炸造成了美国历史上最严重的环境灾难,也是人类历史上第二大石油泄漏事件,三个月内有超过 8 亿升碳氢化合物泄漏到墨西哥湾。由于喷气燃料碳氢化合物的广泛使用,这种化合物混合物已被认为是军事人员接触的最大单一化学物质。先前的动物研究已经证明,喷气燃料(JP-8)暴露能够促进后代疾病易感性的表观遗传跨代遗传。观察到的疾病包括青春期晚期、肾脏、肥胖和多种疾病病理。目前的研究是独特的,旨在识别特定跨代疾病的潜在精子 DNA 甲基化生物标志物。观察结果显示,在祖先暴露于喷气燃料的跨代 F3 代曾孙雄性大鼠中,存在称为表观突变的疾病特异性差异 DNA 甲基化区域 (DMR)。潜在的表观遗传 DMR 生物标志物被发现与青春期晚期、肾脏、肥胖和多种疾病有关,并且发现主要是疾病特异性的。这些疾病特异性 DMR 具有相关基因,这些基因先前已被证明与每种特定疾病相关。因此,种系(即精子)具有环境诱导的祖先衍生的表突变,有可能将疾病易感性跨代传递给后代。 特定疾病的表观遗传生物标志物可以开发为医学诊断,以促进疾病的临床管理,并允许预防性医学治疗。

更新日期:2020-09-06
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