Changes in mammary histology and transcriptome profiles by low-dose exposure to environmental phenols at critical windows of development.
Changes in mammary histology and transcriptome profiles by low-dose exposure to environmental phenols at critical windows of development.
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DOI：
10.1016/j.envres.2016.10.021
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发表时间：
2017-01
影响因子：
8.3
通讯作者：
Chen, Jia
中科院分区：
文献类型：
--
作者：
Gopalakrishnan, Kalpana;Teitelbaum, Susan L.;Lambertini, Luca;Wetmur, James;Manservisi, Fabiana;Falcioni, Laura;Panzacchi, Simona;Belpoggi, Fiorella;Chen, Jia
使用动物模型，暴露于环境化学品与高剂量的乳腺发育改变和癌症风险有关。对与人类接触相当的低剂量的影响仍然知之甚少，特别是在关键的发育窗口期。我们研究了个人护理产品中常用的两种环境酚-对羟基苯甲酸甲酯（MPB）和三氯生（TCS）-在低剂量下对正常乳腺组织学和转录组的影响，模拟人类在发育关键窗口期间的暴露。Sprague-Dawley大鼠在围产期、青春期前和青春期窗口期以及从出生到哺乳期都受到了接触。低剂量暴露于MPB和TCS诱导乳腺组织学（通过Masson三色染色）和转录组（通过微阵列）以窗口特异性方式发生可测量的变化。青春期是对MPB敏感性提高的一个窗口，腺体组织增加，295个基因的表达发生变化，这些基因在DNA复制和细胞周期调节等功能方面具有显著的富集。从出生到哺乳期长期暴露于TCS与脂肪增加和腺体和分泌组织减少有关，在胆固醇合成和脂肪形成等途径中富集的993个基因的表达改变。最后，富集分析显示，MPB和TCS修饰的基因在人类乳腺癌基因特征中过度表达，表明可能与乳腺癌发生有关。这些发现突出了敏感性的关键窗口的问题，可能会提高对环境损害的敏感性，并暗示这些无处不在的环境化学物质对乳腺癌的潜在健康影响。
Exposure to environmental chemicals has been linked to altered mammary development and cancer risk at high doses using animal models. Effects at low doses comparable to human exposure remain poorly understood, especially during critical developmental windows. We investigated the effects of two environmental phenols commonly used in personal care products – methyl paraben (MPB) and triclosan (TCS) – on the histology and transcriptome of normal mammary glands at low doses mimicking human exposure during critical windows of development. Sprague-Dawley rats were exposed during perinatal, prepubertal and pubertal windows, as well as from birth to lactation. Low-dose exposure to MPB and TCS induced measurable changes in both mammary histology (by Masson’s Trichrome Stain) and transcriptome (by microarrays) in a window-specific fashion. Puberty represented a window of heightened sensitivity to MPB, with increased glandular tissue and changes of expression in 295 genes with significant enrichment in functions such as DNA replication and cell cycle regulation. Long-term exposure to TCS from birth to lactation was associated with increased adipose and reduced glandular and secretory tissue, with expression alterations in 993 genes enriched in pathways such as cholesterol synthesis and adipogenesis. Finally, enrichment analyses revealed that genes modified by MPB and TCS were over-represented in human breast cancer gene signatures, suggesting possible links with breast carcinogenesis. These findings highlight the issues of critical windows of susceptibility that may confer heightened sensitivity to environmental insults and implicate the potential health effects of these ubiquitous environmental chemicals in breast cancer.
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内分泌破坏三氯生的作用对怀孕大鼠的胎盘。
影响因子：
3.7
作者：
Feng Y;Zhang P;Zhang Z;Shi J;Jiao Z;Shao B
通讯作者：
Shao B
影响因子：
2.5
作者：
Macon, Madisa B.;Fenton, Suzanne E.
通讯作者：
Fenton, Suzanne E.
DOI：
10.1146/annurev-pharmtox-010611-134659
发表时间：
2012
影响因子：
12.5
作者：
Fenton SE;Reed C;Newbold RR
通讯作者：
Newbold RR
影响因子：
3.6
作者：
Biemann R;Fischer B;Navarrete Santos A
通讯作者：
Navarrete Santos A
DOI：
10.1177/1559325815610760
发表时间：
2015-10
期刊：
Dose-response : a publication of International Hormesis Society
影响因子：
--
作者：
Gioiosa L;Palanza P;Parmigiani S;Vom Saal FS
通讯作者：
Vom Saal FS