Department of Environmental and Global Health, University of Florida, Gainesville, FL, USA.
Department of Pharmacology, Wayne State University, Detroit, MI, USA.
J Dev Orig Health Dis. 2024 Oct 14;15:e22. doi: 10.1017/S2040174424000229.
Exposure to 2,3,7,8-tetrachlorodibenzo--dioxin (TCDD), an environmental endocrine disruptor and model AhR agonist, is linked to skeletal abnormalities, cardiac edema, stunted growth rate, altered metabolism, and neurobehavioral deficits. We have previously reported transgenerational reproductive outcomes of developmental TCDD exposure in adult zebrafish (), an NIH-validated model for developmental and generational toxicology. Using the same paradigm of sublethal TCDD exposure (50 pg/ml) at both 3 and 7 weeks post fertilization (wpf), we investigated several novel endpoints, including longitudinal morphometrics and anxiety-linked behavior, in fish exposed as juveniles. We also assessed developmental abnormalities and neurobehavior in their F larval offspring. TCDD exposure induced timepoint-dependent decreases in several craniofacial and trunk morphometrics across juvenile development. In early adulthood, however, only exposed males underwent a transient period of compensatory growth, ending between 7 and 12 months post fertilization (mpf). At 12 mpf, exposed adult fish of both sexes displayed increased exploratory behaviors in a novel tank test. The F offspring of parents exposed at both 3 and 7 wpf were hyperactive, but neurobehavioral outcomes diverged depending on parental exposure window. F exposure-lineage larvae had increased rates of edema and skeletal abnormalities, but fewer unhatched larvae compared to controls. Parent- and timepoint-specific effects of exposure on abnormality rate were also evaluated; these outcomes were considerably less severe. Our novel behavioral findings expand current knowledge of the long-term and intergenerational consequences of early-life TCDD exposure in a zebrafish model, in addition to delineating minor longitudinal morphometric changes in exposed fish and abnormalities in larval offspring.
接触 2,3,7,8-四氯二苯并对二恶英（TCDD），一种环境内分泌干扰物和模型 AhR 激动剂，与骨骼异常、心脏水肿、生长速度减慢、代谢改变和神经行为缺陷有关。我们之前报道了发育性 TCDD 暴露对成年斑马鱼（）的代际生殖结果，斑马鱼是一种经过 NIH 验证的发育和代际毒理学模型。使用相同的亚致死 TCDD 暴露（50 pg/ml）范式，在受精后 3 周和 7 周（wpf），我们研究了几种新的终点，包括纵向形态测量和与焦虑相关的行为，在幼年时期暴露的鱼类中。我们还评估了它们的 F 幼虫后代的发育异常和神经行为。TCDD 暴露诱导了几个颅面和躯干形态测量在幼鱼发育过程中的时间依赖性下降。然而，在成年早期，只有暴露的雄性经历了一个短暂的补偿性生长期，在受精后 7 至 12 个月（mpf）结束。在 12 mpf 时，暴露于 3 周和 7 周的成年鱼的雄性和雌性都表现出在新的鱼缸测试中探索行为增加。父母在 3 周和 7 周时暴露的 F 后代是多动的，但神经行为结果取决于父母暴露窗口的不同而不同。与对照相比，F 暴露系幼虫的水肿和骨骼异常率增加，但未孵化的幼虫较少。还评估了暴露对异常率的父母和时间点特异性影响；这些结果要轻微得多。我们的新行为学发现扩展了目前对斑马鱼模型中早期生命 TCDD 暴露的长期和代际后果的认识，除了描述暴露鱼类的轻微纵向形态变化和幼虫后代的异常外。
