Department of Biological Sciences, North Carolina State University, Raleigh, NC, 27695, USA.
Department of Biological Sciences, North Carolina State University, Raleigh, NC, 27695, USA; National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA.
Neurotoxicology. 2019 Dec;75:136-147. doi: 10.1016/j.neuro.2019.09.003. Epub 2019 Sep 18.
Tetrabromobisphenol A (TBBPA) has become a ubiquitous indoor contaminant due to its widespread use as an additive flame retardant in consumer products. Reported evidence of endocrine disruption and accumulation of TBBPA in brain tissue has raised concerns regarding its potential effects on neurodevelopment and behavior. The goal of the present study was to examine the impact of developmental TBBPA exposure, across a wide range of doses, on sexually dimorphic non-reproductive behaviors in male and female Wistar rats. We first ran a pilot study using a single TBBPA dose hypothesized to produce behavioral effects. Wistar rat dams were orally exposed using cookie treats to 0 or 0.1 mg TBBPA/kg bw daily from gestational day (GD) 9 to postnatal day (PND) 21 to assess offspring (both sexes) activity and anxiety-related behaviors. Significant effects were evident in females, with exposure increasing activity levels. Thus, this dose was used as the lowest TBBPA dose in a subsequent, larger study conducted as part of a comprehensive assessment of TBBPA toxicity. Animals were exposed to 0, 0.1, 25, or 250 mg TBBPA/kg bw daily by oral gavage starting on GD 6 through PND 90 (dosed dams GD 6 - PND 21, dosed offspring PND 22 - PND 90). Significant behavioral findings were observed for male offspring, with increased anxiety-like behavior as the primary phenotype. These findings demonstrate that exposure to environmental contaminants, like TBBPA, can have sex-specific effects on behavior highlighting the vulnerability of the developing brain.
四溴双酚 A（TBBPA）作为一种常见的室内污染物，由于其作为消费品添加剂阻燃剂的广泛应用而无处不在。已有研究报道表明 TBBPA 具有内分泌干扰作用，并在脑组织中积累，这引发了人们对其潜在神经发育和行为影响的关注。本研究的目的是研究在广泛剂量范围内，发育过程中 TBBPA 暴露对雄性和雌性 Wistar 大鼠的性别二态非生殖行为的影响。我们首先进行了一项初步研究，使用假设会产生行为效应的单一 TBBPA 剂量。Wistar 大鼠母体通过饼干处理进行口服暴露，每天接受 0 或 0.1mg TBBPA/kg bw 的剂量，从妊娠第 9 天（GD）到产后第 21 天（PND），以评估后代（雌雄两性）的活动和焦虑相关行为。在雌性中观察到明显的效应，暴露增加了活动水平。因此，该剂量被用作后续更大规模研究中的最低 TBBPA 剂量，该研究作为 TBBPA 毒性综合评估的一部分进行。动物从 GD 6 到 PND 90 每天通过口服灌胃接受 0、0.1、25 或 250mg TBBPA/kg bw 的剂量，处理母体 GD 6 - PND 21，处理后代 PND 22 - PND 90。雄性后代观察到显著的行为发现，表现为焦虑样行为增加作为主要表型。这些发现表明，暴露于环境污染物（如 TBBPA）会对行为产生性别特异性影响，突出了发育中大脑的脆弱性。
