Epigenetic Memory of Early-Life Parental Perturbation: Dopamine Decrease and DNA Methylation Changes in Offspring
Epigenetic Memory of Early-Life Parental Perturbation: Dopamine Decrease and DNA Methylation Changes in Offspring
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DOI：
10.1155/2019/1472623
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发表时间：
2019-01-01
影响因子：
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通讯作者：
Gabbianelli, Rosita
中科院分区：
文献类型：
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作者：
Bordoni, Laura;Nasuti, Cinzia;Gabbianelli, Rosita
在大鼠中，早期暴露于氯菊酯（出生后第6天至出生后第21天）与多巴胺能神经变性的长期发展有关。在这里，我们首先研究了在出生后早期暴露于氯菊酯（一种氧化应激源）后观察到的多巴胺减少是否会损害未经处理的后代大脑中的多巴胺水平。其次，我们评估了该不良事件是否影响直接暴露大鼠（F0）及其未处理后代（F1）的表观基因组。结果表明，早期生活中暴露于压力源与成年后整体DNA甲基化和羟甲基化的变化有关。此外，父母暴露导致从父母或仅母亲早期生活治疗所生的后代（F1）中多巴胺水平显著降低（分别为72.72%和47.35%）。与对照组相比，来自暴露母亲的约2/3的幼崽显示多巴胺水平显著降低。整体DNA甲基化和羟甲基化损伤与表现出多巴胺减少的F1幼仔相关。这项研究提供了关键的证据，出生后暴露于氯菊酯的代际效应，强调这种外源性物质可以影响早期生活的父母干扰后代健康的表观遗传记忆。
Early-life exposure (from postnatal day 6 to postnatal day 21) to permethrin has been associated with long-term development of dopaminergic neurodegeneration in rats. Here, we first investigated if the dopamine decrease observed following early postnatal exposure to permethrin, an oxidative stressor, can impair the dopamine level in the brain of their untreated offspring. Secondly, we evaluated whether this adverse event affects the epigenome of both directly exposed rats (F0) and their untreated offspring (F1). The results show that early-life exposure to the stressor is associated with changes in global DNA methylation and hydroxymethylation in adult age. Furthermore, parental exposure leads to a significant reduction in dopamine level in the offspring (F1) born from parents or just mothers early-life treated (72.72% and 47.35%, respectively). About 2/3 of pups from exposed mothers showed a significant reduction in dopamine level compared to controls. Global DNA methylation and hydroxymethylation impairment was associated with the F1 pups that showed reduced dopamine. This study provides pivotal evidences on intergenerational effects of postnatal exposure to permethrin emphasizing that this xenobiotic can influence the epigenetic memory of early-life parental perturbations disturbing offspring health.