Molecular and Environmental Toxicology Center, and Pharmaceutical Sciences, University of Wisconsin, Madison, Wisconsin 53705-2222.
Toxicol Sci. 2014 Apr;138(2):403-11. doi: 10.1093/toxsci/kfu006. Epub 2014 Jan 27.
2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD) has been associated with many disease states in humans. A rising concern is that exposure early in life can lead to adult toxicity and toxicity in subsequent generations. Juvenile zebrafish exposed to TCDD (50 pg/ml in water; 1 h exposure) at 3 and 7 weeks post fertilization showed toxicity only later in adulthood. We have maintained the offspring of these exposed F₀ fish to determine whether we could find adverse affects in the next two generations of F₁ and F₂ offspring. TCDD exposure produced a significantly higher female:male ratio in all three generations. Scoliosis-like axial skeleton abnormalities, not normally observed in controls, were present in the F₁ and F₂ generations descended from the treated F₀ founders. Egg release and fertilization success were reduced in the TCDD lineage F₁ and F₂ generations. This reduction in fertility in the TCDD lineage F₂ generation could be attributed to alterations in the F₂ males. Using zebrafish as a model allowed the simultaneous maintenance of different generations with relatively small space and costs. The zebrafish showed clear signs of transgenerational responses persisting into generations never directly exposed to TCDD.
2,3,7,8 四氯二苯并对二恶英（TCDD）与人类的许多疾病状态有关。人们越来越关注的是，早期暴露于 TCDD 会导致成年毒性和后代毒性。在受精后 3 周和 7 周时，暴露于 TCDD（水中 50 pg/ml；1 小时暴露）的幼年斑马鱼仅在成年后表现出毒性。我们一直维持着这些暴露的 F₀ 鱼的后代，以确定是否可以在下两代 F₁ 和 F₂ 后代中发现不良影响。TCDD 暴露在所有三代中都产生了明显更高的雌性：雄性比例。在源自处理的 F₀ 创始鱼的 F₁ 和 F₂ 代中，出现了通常在对照组中观察不到的脊柱侧凸样轴骨骼异常。在 TCDD 谱系的 F₁ 和 F₂ 代中，卵释放和受精成功率降低。TCDD 谱系 F₂ 代的这种生育能力降低可归因于 F₂ 雄性的改变。使用斑马鱼作为模型，可以在相对较小的空间和成本下同时维持不同的代。斑马鱼表现出明显的跨代反应迹象，这些反应持续到从未直接暴露于 TCDD 的代。
