Assessment of parental benzo[a]pyrene exposure-induced cross-generational neurotoxicity and changes in offspring sperm DNA methylome in medaka fish.
Assessment of parental benzo[a]pyrene exposure-induced cross-generational neurotoxicity and changes in offspring sperm DNA methylome in medaka fish.
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DOI：
10.1093/eep/dvac013
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发表时间：
2022
影响因子：
3.8
通讯作者：
中科院分区：
文献类型：
--
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以往的研究表明，DNA甲基化的变化可以作为潜在的基因组标记的环境苯并[a]芘（BaP）暴露和代际遗传的各种生理损伤（如肥胖和生殖病理）。苯并（a）芘作为一种典型的芳香烃污染物，直接暴露可引起神经毒性.为了揭示BaP诱导的淡水青鳉骨表型的遗传机制，我们对F1精子进行了全基因组亚硫酸氢盐测序，并确定了776个差异甲基化基因（DMG）。免疫途径分析显示，DMG显着丰富的神经元发育和功能相关的途径。因此，假设母体BaP暴露（1 μg/l，21天）会导致后代神经毒性。此外，研究了精子甲基化作为神经毒性表型指标的可能性。分析了F0成虫脑和F1幼虫的BaP诱导的直接和遗传毒性。乙酰胆碱酯酶活性显着降低的幼虫，连同游泳速度下降。分子分析显示，与神经元发育和生长（α 1-微管蛋白，mbp，syn 2a，shh和gap 43）以及大脑发育（dlx 2，otx 2和krox-20）的标记基因普遍下调的F1幼虫（孵化后3天）。虽然环境相关浓度的亲源苯并（a）芘暴露可诱导发育中幼虫的神经毒性，但暴露的F0代成虫的脑功能不受影响。这表明幼虫的发育神经毒性可能是由于神经元发育和分化受损，导致大脑生长延迟。目前的研究表明，苯并（a）芘在环境中可能对健康产生的不利影响比目前所了解的更为广泛。因此，多代BaP毒性的可能性应纳入环境风险评估。
Previous studies have revealed that DNA methylation changes could serve as potential genomic markers for environmental benzo[a]pyrene (BaP) exposure and intergenerational inheritance of various physiological impairments (e.g. obesity and reproductive pathologies). As a typical aromatic hydrocarbon pollutant, direct BaP exposure has been shown to induce neurotoxicity. To unravel the inheritance mechanisms of the BaP-induced bone phenotype in freshwater medaka, we conducted whole-genome bisulfite sequencing of F1 sperm and identified 776 differentially methylated genes (DMGs). Ingenuity pathway analysis revealed that DMGs were significantly enriched in pathways associated with neuronal development and function. Therefore, it was hypothesized that parental BaP exposure (1 μg/l, 21 days) causes offspring neurotoxicity. Furthermore, the possibility for sperm methylation as an indicator for a neurotoxic phenotype was investigated. The F0 adult brains and F1 larvae were analyzed for BaP-induced direct and inherited toxicity. Acetylcholinesterase activity was significantly reduced in the larvae, together with decreased swimming velocity. Molecular analysis revealed that the marker genes associated with neuron development and growth (alpha1-tubulin, mbp, syn2a, shh, and gap43) as well as brain development (dlx2, otx2, and krox-20) were universally downregulated in the F1 larvae (3 days post-hatching). While parental BaP exposure at an environmentally relevant concentration could induce neurotoxicity in the developing larvae, the brain function of the exposed F0 adults was unaffected. This indicates that developmental neurotoxicity in larvae may result from impaired neuronal development and differentiation, causing delayed brain growth. The present study demonstrates that the possible adverse health effects of BaP in the environment are more extensive than currently understood. Thus, the possibility of multigenerational BaP toxicity should be included in environmental risk assessments.
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影响因子：
3.8
作者：
Bisson, M;Hontela, A
通讯作者：
Hontela, A
影响因子：
2.9
作者：
DANGE, AD;MASUREKAR, VB
通讯作者：
MASUREKAR, VB
影响因子：
4.3
作者：
Fang X;Thornton C;Scheffler BE;Willett KL
通讯作者：
Willett KL
影响因子：
64.5
作者：
BASI, GS;JACOBSON, RD;SKENE, JHP
通讯作者：
SKENE, JHP
影响因子：
4.1
作者：
GILLESPIE, CS;WILSON, R;BROPHY, PJ
通讯作者：
BROPHY, PJ