Laboratory of Evolutionary and Adaptive Physiology, Institute of Life, Earth, and the Environment, University of Namur, 61 Rue de Bruxelles, 5000, Namur, Belgium.
Laboratory of Evolutionary and Adaptive Physiology, Institute of Life, Earth, and the Environment, University of Namur, 61 Rue de Bruxelles, 5000, Namur, Belgium.
Aquat Toxicol. 2023 May;258:106474. doi: 10.1016/j.aquatox.2023.106474. Epub 2023 Mar 4.
Methylmercury (MeHg) is a ubiquitous bioaccumulative neurotoxicant present in aquatic ecosystems. It is known to alter behaviors, sensory functions and learning abilities in fish and other vertebrates. Developmental and early-life stages exposure to MeHg can lead to brain damage with immediate consequences on larvae behavior, but may also induce long term effects in adults after a detoxification period. However, very little is known about developmental origin of behavioral impairment in adults due to early exposure to MeHg. The aim of this study is to assess whether early-life MeHg exposure induces immediate and/or delayed effects on behaviors, related genes expression and DNA methylation (one of epigenetic mechanisms). To reach this goal, newly hatched larvae of mangrove rivulus fish, Kryptolebias marmoratus, were exposed to two sub-lethal concentrations of MeHg (90 μg/L and 135 µg/L) for 7 days, and immediate and delayed effects were assessed respectively in 7 dph (days post-hatching) and 90 dph fish. This species naturally produces isogenic lineages due to its self-fertilizing reproduction system, which is unique among vertebrates. It allows to study how environment stressors can influence organism's phenotype while minimizing genetic variability. As results, both MeHg exposures are associated with a decreased foraging efficiency and thigmotaxis, and a dose-dependent reduction in larvae locomotor activity. Regarding molecular analysis in larvae whole bodies, both MeHg exposures induced significant decreased expression of DNMT3a, MAOA, MeCP2 and NIPBL, and significant increase of GSS, but none of those genes underwent methylation changes in targeted CpGs. None of significant behavioral and molecular impairments observed in 7-dph larvae were found in 90-dph adults, which highlight a distinction between immediate and delayed effects of developmental MeHg exposure. Our results suggest implications of aminergic system and its neurotransmitters, redox/methylation trade-off and possibly other epigenetic mechanisms in MeHg neurotoxicity underlying behavioral alterations in rivulus.
甲基汞（MeHg）是一种普遍存在的生物蓄积性神经毒素，存在于水生生态系统中。它已知会改变鱼类和其他脊椎动物的行为、感觉功能和学习能力。在发育和生命早期阶段暴露于 MeHg 会导致大脑损伤，立即影响幼虫的行为，但在解毒期后，也可能在成年后引起长期影响。然而，由于早期暴露于 MeHg，对于成年期行为障碍的发育起源知之甚少。本研究旨在评估生命早期 MeHg 暴露是否会对行为、相关基因表达和 DNA 甲基化（一种表观遗传机制）产生即时和/或延迟效应。为了达到这个目标，孵化后的红树林罗非鱼（Kryptolebias marmoratus）幼虫被暴露于两种亚致死浓度的 MeHg（90μg/L 和 135μg/L）7 天，分别在 7 天（孵化后）和 90 天评估即时和延迟效应。由于其自受精繁殖系统，该物种自然产生同系物，这在脊椎动物中是独一无二的。它允许研究环境胁迫因子如何影响生物体的表型，同时最小化遗传变异性。结果表明，两种 MeHg 暴露都与觅食效率和触壁行为降低以及幼虫运动活性的剂量依赖性降低有关。关于幼虫全身的分子分析，两种 MeHg 暴露都导致 DNMT3a、MAOA、MeCP2 和 NIPBL 的表达显著降低，GSS 显著增加，但没有一个基因在靶向 CpG 中发生甲基化变化。在 7 天龄幼虫中观察到的任何显著行为和分子损伤都没有在 90 天龄成虫中发现，这突出了发育性 MeHg 暴露的即时和延迟效应之间的区别。我们的结果表明，在 MeHg 神经毒性引起的罗非鱼行为改变中，涉及到胺能系统及其神经递质、氧化还原/甲基化权衡和可能的其他表观遗传机制。
