Prenatal bisphenol A (BPA) exposure alters the transcriptome of the neonate rat amygdala in a sex-specific manner: a CLARITY-BPA consortium study.
Prenatal bisphenol A (BPA) exposure alters the transcriptome of the neonate rat amygdala in a sex-specific manner: a CLARITY-BPA consortium study.
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DOI：
10.1016/j.neuro.2017.10.005
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发表时间：
2018-03
期刊：
影响因子：
3.4
通讯作者：
Patisaul HB
中科院分区：
文献类型：
--
作者：
Arambula SE;Jima D;Patisaul HB
双酚A（BPA）是一种广泛公认的内分泌干扰物，在许多家庭用品中普遍存在。由于实验和流行病学数据表明，产前BPA暴露与儿童情感行为改变之间存在联系，即使低于当前美国FDA无明显不良作用水平（NOAEL）5 mg/kg体重（bw）/天，人们担心生命早期暴露可能会改变神经发育。目前的研究是作为联合BPA（BPA毒性学术和监管见解联盟）计划的一部分进行的，并检查了出生后第一天（PND）的完整杏仁核转录组，假设产前BPA暴露会改变性别特异性情感行为的基因和途径的表达。NCTR Sprague-Dawley母鼠从妊娠第6天至分娩期间，灌胃BPA（2.5、25、250、2500或25000 μg/kg bw /天）、参考雌激素（0.05或0.5 μg炔雌醇（EE 2）/kg bw/天）或溶剂。显微解剖PND 1杏仁核，并使用qRT-PCR（所有暴露组）和RNAseq（溶媒、25和250 μg BPA以及仅0.5 μg EE 2组）评估基因表达。我们的研究结果表明，产前BPA暴露可以破坏新生儿杏仁核的转录组，剂量低于FDA NOAEL，以性别特异性的方式，并表明女性杏仁核可能对胎儿发育期间的BPA暴露更敏感。我们还提供了额外的证据，发育BPA暴露可以干扰雌激素，催产素和加压素信号通路在发育中的大脑和改变突触组织和传输的关键信号通路。
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.
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影响因子：
10.4
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