Impact of a bisphenol A, F, and S mixture and maternal care on the brain transcriptome of rat dams and pups.

Impact of a bisphenol A, F, and S mixture and maternal care on the brain transcriptome of rat dams and pups.
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DOI:
10.1016/j.neuro.2022.08.014
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发表时间:
2022-12
期刊:
影响因子:
3.4
通讯作者:
Champagne, F. A.
Champagne, F. A.
中科院分区:
医学3区
文献类型:
--
作者:
Lapp, H. E.;Margolis, A. E.;Champagne, F. A.

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含有BPA结构类似物替代品的产品已经增加,以应对公众对BPA不利影响的日益关注。尽管人类经常接触双酚的混合物,但很少有研究检查产前接触双酚A替代品或双酚混合物的影响。在本研究中,我们使用Tag RNA测序研究了妊娠期间暴露于环境相关的低剂量(每天150 ug/kg体重)BPA,BPS和BPF混合物对Long-Evans幼崽和母鼠脑转录组的影响。我们还研究了舔母鼠和梳理之间的关联,这也对幼鼠的神经发育和转录组有持久的影响。舔和梳理和转录组之间的关联是区域特异性的,与下丘脑有最大数量的差异表达的基因与舔和梳理在母鼠和幼鼠。产前双酚暴露对基因表达也有区域特异性影响,幼鼠基因表达比母鼠基因表达受到更强烈的影响。在母鼠中,前边缘皮层有最多的与产前双酚暴露相关的差异表达基因。产前双酚暴露改变了幼鼠2000多个基因的表达,其中大部分来自幼鼠杏仁核。我们使用基因集富集分析(GSEA)来评估每个区域的基因本体生物过程的富集。顶级GSEA术语是多样的,不同的大脑区域,包括已知与类固醇激素调节,纤毛相关的术语,代谢/生物合成过程术语和免疫术语有很强的关联的过程。最后,假设驱动的基因相关的雌激素反应,父母的行为,和基因表达的表观遗传调控的分析显示区域特异性表达与舔和梳理和双酚暴露,是不同的母鼠和幼鼠。这些数据突出了双酚对多种生理过程的影响,这些生理过程高度依赖于暴露的时间(产前与成年)和大脑区域,并重申了多种环境和经验因素在塑造大脑中的作用。
Products containing BPA structural analog replacements have increased in response to growing public concern over adverse effects of BPA. Although humans are regularly exposed to a mixture of bisphenols, few studies have examined effects of prenatal exposure to BPA alternatives or bisphenol mixtures. In the present study, we investigate the effect of exposure to an environmentally-relevant, low-dose (150 ug/kg body weight per day) mixture of BPA, BPS, and BPF during gestation on the brain transcriptome in Long-Evans pups and dams using Tag RNA-sequencing. We also examined the association between dam licking and grooming, which also has enduring effects on pup neural development, and the transcriptomes. Associations between licking and grooming and the transcriptome were region-specific, with the hypothalamus having the greatest number of differentially expressed genes associated with licking and grooming in both dams and pups. Prenatal bisphenol exposure also had region-specific effects on gene expression and pup gene expression was affected more robustly than dam gene expression. In dams, the prelimbic cortex had the greatest number of differentially expressed genes associated with prenatal bisphenol exposure. Prenatal bisphenol exposure changed the expression of over 2000 genes in pups, with the majority being from the pup amygdala. We used Gene Set Enrichment Analysis (GSEA) to asses enrichment of gene ontology biological processes for each region. Top GSEA terms were diverse and varied by brain region and included processes known to have strong associations with steroid hormone regulation, cilium-related terms, metabolic/biosynthetic process terms, and immune terms. Finally, hypothesis-driven analysis of genes related to estrogen response, parental behavior, and epigenetic regulation of gene expression revealed region-specific expression associated with licking and grooming and bisphenol exposure that were distinct in dams and pups. These data highlight the effects of bisphenols on multiple physiological process that are highly dependent on timing of exposure (prenatal vs. adulthood) and brain region, and reiterate the contributions of multiple environmental and experiential factors in shaping the brain.
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