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Prenatal bisphenol A (BPA) exposure alters the transcriptome of the neonate rat amygdala in a sex-specific manner: a CLARITY-BPA consortium study
NeuroToxicology ( IF 3.4 ) Pub Date : 2017-10-28 , DOI: 10.1016/j.neuro.2017.10.005
Sheryl E. Arambula , Dereje Jima , Heather B. Patisaul

Bisphenol A (BPA) is a widely recognized endocrine disruptor prevalent in many household items. Because experimental and epidemiological data suggest links between prenatal BPA exposure and altered affective behaviors in children, even at levels below the current US FDA No Observed Adverse Effect Level (NOAEL) of 5 mg/kg body weight (bw)/day, there is concern that early life exposure may alter neurodevelopment. The current study was conducted as part of the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) program and examined the full amygdalar transcriptome on postnatal day (PND) 1, with the hypothesis that prenatal BPA exposure would alter the expression of genes and pathways fundamental to sex-specific affective behaviors. NCTR Sprague-Dawley dams were gavaged from gestational day 6 until parturition with BPA (2.5, 25, 250, 2500, or 25000 μg/kg bw/day), a reference estrogen (0.05 or 0.5 μg ethinyl estradiol (EE2)/kg bw/day), or vehicle. PND 1 amygdalae were microdissected and gene expression was assessed with qRT-PCR (all exposure groups) and RNAseq (vehicle, 25 and 250 μg BPA, and 0.5 μg EE2 groups only). Our results demonstrate that that prenatal BPA exposure can disrupt the transcriptome of the neonate amygdala, at doses below the FDA NOAEL, in a sex-specific manner and indicate that the female amygdala may be more sensitive to BPA exposure during fetal development. We also provide additional evidence that developmental BPA exposure can interfere with estrogen, oxytocin, and vasopressin signaling pathways in the developing brain and alter signaling pathways critical for synaptic organization and transmission.



中文翻译:

产前双酚A(BPA)暴露以性别特异性方式改变新生大鼠杏仁核的转录组:一项CLARITY-BPA财团研究

双酚A(BPA)是一种广泛认可的内分泌干扰物,广泛存在于许多家庭用品中。由于实验和流行病学数据表明,即使在低于目前美国FDA未观察到的不良反应水平(NOAEL)5 mg / kg体重(bw)/天的水平下,产前BPA暴露与儿童情感行为改变之间也存在关联,因此值得关注早期接触可能会改变神经发育。目前的研究是CLARITY-BPA(对BPA毒性的学术研究和法规洞察力联动的联盟)计划的一部分,并检查了产后第1天(PND)的完整杏仁核转录组,并假设产前BPA暴露会改变BPA的表达。性别特异性行为的基本基因和途径。从妊娠第6天到用BPA分娩,对NCTR Sprague-Dawley水坝进行了管控(2。2)/ kg bw /天)或车辆。PND 1个被杏仁显微解剖和基因表达用的qRT-PCR(所有剂量组)和RNA测序评估(车辆,25和250μgBPA,和0.5微克EE 2个仅基团)。我们的结果表明,在低于FDA NOAEL的剂量下,产前BPA暴露可以以性别特异性方式破坏新生儿杏仁核的转录组,并表明雌性杏仁核可能在胎儿发育过程中对BPA暴露更敏感。我们还提供了其他证据,表明发育中的BPA暴露可能会干扰发育中的大脑中的雌激素,催产素和加压素信号传导途径,并改变对于突触组织和传播至关重要的信号传导途径。

更新日期:2017-10-28
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