Facultad de Ciencias, Universidad Autónoma de Baja California (UABC), Carretera Tijuana-Ensenada 3917, Playitas, 22860 Ensenada, B.C., Mexico.
Instituto de Investigaciones Oceanológicas, Universidad Autónoma de Baja California, Ensenada, Baja California, Mexico.
Toxicol Appl Pharmacol. 2020 Jun 1;396:115002. doi: 10.1016/j.taap.2020.115002. Epub 2020 Apr 8.
The ability of environmental pollutants to alter the epigenome with resultant development of behavioral alterations has received more attention in recent years. These alterations can be transmitted and affect later generations that have not been directly in contact with the contaminant. Arsenic (As) is a neurotoxicant and potent epigenetic disruptor that is widespread in the environment; however, the precise potential of As to produce transgenerational effects is unknown. Our study focused on the possible transgenerational effects on behavior by ancestral exposure to doses relevant to the environment of As, and the epigenetic mechanisms that could be involved. Embryos of F0 (ancestral generation) were directly exposed to 50 or 500 ppb of As for 150 days. F0 adults were raised to produce the F1 generation (intergeneration) and subsequently the F2 generation (transgeneration). We evaluated motor and cognitive behavior, neurodevelopment-related genes, and epigenetic markers on the F0 and F2 generation. As proposed in our hypothesis, ancestral arsenic exposure altered motor activity through the development and increased anxiety-like behaviors which were transmitted to the F2 generation. Additionally, we found a reduction in brain-derived neurotrophic factor expression between the F0 and F2 generation, and an increase in methylation on histone H3K4me3 in the nervous system.
近年来，环境污染物改变表观基因组，进而导致行为改变的能力引起了更多关注。这些改变可以传递，并影响未直接接触污染物的后代。砷（As）是一种神经毒素和有效的表观遗传干扰物，广泛存在于环境中；然而，As 产生跨代效应的确切潜力尚不清楚。我们的研究重点是祖先暴露于与环境相关的 As 剂量下，可能产生的跨代行为效应，以及可能涉及的表观遗传机制。F0（祖先代）胚胎直接暴露于 50 或 500 ppb 的 As 中 150 天。F0 成年动物被饲养以产生 F1 代（代际），随后产生 F2 代（跨代）。我们评估了 F0 和 F2 代的运动和认知行为、神经发育相关基因和表观遗传标记。正如我们假设的那样，祖先砷暴露通过发育改变了运动活动，并增加了焦虑样行为，这些行为传递给了 F2 代。此外，我们发现在 F0 和 F2 代之间脑源性神经营养因子表达减少，并且神经系统中组蛋白 H3K4me3 的甲基化增加。
