Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695, USA; WM Keck Center for Behavioral Biology, North Carolina State University, Raleigh, NC 27695, USA.
Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695, USA.
Neurotoxicology. 2017 Dec;63:33-42. doi: 10.1016/j.neuro.2017.09.002. Epub 2017 Sep 7.
Bisphenol A (BPA) is a high volume endocrine disrupting chemical found in a wide variety of products including plastics and epoxy resins. Human exposure is nearly ubiquitous, and higher in children than adults. Because BPA has been reported to interfere with sex steroid hormone signaling, there is concern that developmental exposure, even at levels below the current FDA No Observed Adverse Effect Level (NOAEL) of 5mg/kg body weight (bw)/day, can disrupt brain sexual differentiation. The current studies were conducted as part of the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) program and tested the hypothesis that perinatal BPA exposure would induce morphological changes in hormone sensitive, sexually dimorphic brain regions. Sprague-Dawley rats were randomly assigned to 5 groups: BPA (2.5, 25, or 2500μg/kgbw/day), a reference estrogen (0.5μg ethinylestradiol (EE)/kgbw/day), or vehicle. Exposure occurred by gavage to the dam from gestational day 6 until parturition, and then to the offspring from birth through weaning. Unbiased stereology was used to quantify the volume of the sexually dimorphic nucleus (SDN), the anteroventral periventricular nucleus (AVPV), the posterodorsal portion of the medial amygdala (MePD), and the locus coeruleus (LC) at postnatal day 28. No appreciable effects of BPA were observed on the volume of the SDN or LC. However, AVPV volume was enlarged in both sexes, even at levels below the FDA NOAEL. Collectively, these data suggest the developing brain is vulnerable to endocrine disruption by BPA at exposure levels below previous estimates by regulatory agencies.
双酚 A（BPA）是一种高容量的内分泌干扰化学物质，存在于多种产品中，包括塑料和环氧树脂。人类接触几乎无处不在，儿童的接触量高于成年人。由于 BPA 已被报道会干扰性激素信号，因此人们担心即使在低于当前 FDA 无观察到不良效应水平（NOAEL）5mg/kg 体重（bw）/天的水平下，发育过程中的暴露也会干扰大脑的性别分化。目前的研究是作为 CLARITY-BPA（将学术和监管对 BPA 毒性的见解联系起来的联盟）计划的一部分进行的，该研究检验了这样一个假设，即围产期 BPA 暴露会诱导对激素敏感的、性别二态性的大脑区域的形态变化。Sprague-Dawley 大鼠被随机分配到 5 个组：BPA（2.5、25 或 2500μg/kgbw/day）、参考雌激素（0.5μg 乙炔雌二醇（EE）/kgbw/day）或载体。暴露是通过灌胃向母体从妊娠第 6 天持续到分娩，然后向后代从出生持续到断奶。使用无偏立体学方法来定量性别二态性核（SDN）、前腹侧室旁核（AVPV）、内侧杏仁核后背部（MePD）和蓝斑（LC）的体积，在出生后第 28 天进行。BPA 对 SDN 或 LC 的体积没有明显影响。然而，AVPV 体积在两性中都增大了，即使在低于 FDA 的 NOAEL 水平。总的来说，这些数据表明，发育中的大脑容易受到 BPA 的内分泌干扰，而之前监管机构的估计则低于这一水平。
