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首页> 外文期刊>Environmental research >Changes in mammary histology and transcriptome profiles by low-dose exposure to environmental phenols at critical windows of development
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Changes in mammary histology and transcriptome profiles by low-dose exposure to environmental phenols at critical windows of development

机译：低剂量暴露于环境关键时期的环境酚对乳腺组织学和转录组谱的影响

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摘要

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.
机译：使用动物模型，高剂量暴露于环境化学物质与改变的乳腺发育和癌症风险有关。与人类暴露相当的低剂量效应仍然知之甚少，尤其是在关键的发育期。我们调查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）-对低剂量的正常乳腺的组织学和转录组的影响，模拟了人类在关键的发育窗口期间的暴露情况。 Sprague-Dawley大鼠在围产期，青春期前和青春期期间以及从出生到哺乳期均暴露。低剂量暴露于MPB和TCS会以窗口特定的方式在乳腺组织学（通过Masson Trichrome Stain）和转录组（通过微阵列）中引起可测量的变化。青春期代表了对MPB敏感性增强的窗口，腺体组织增加，并且295个基因的表达发生变化，并显着丰富了DNA复制和细胞周期调控等功能。从出生到哺乳期长期接触TCS与脂肪增多，腺体和分泌组织减少有关，与993种基因的表达改变有关，这些基因富含胆固醇合成和脂肪形成等途径。最后，富集分析显示，MPB和TCS修饰的基因在人乳腺癌基因签名中过分代表，提示可能与乳腺癌的致癌作用有关。这些发现凸显了易感性的关键窗口问题，这些问题可能使人们对环境侵害的敏感性增强，并暗示这些普遍存在的环境化学物质对乳腺癌的潜在健康影响。

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  • 来源
    《Environmental research》 |2017年第1期|233-243|共11页
  • 作者

    Kalpana Gopalakrishnan; Susan L. Teitelbaum; Luca Lambertini; James Wetmur; Fabiana Manservisi; Laura Falcioni; Simona Panzacchi; Fiorella Belpoggi; Jia Chen;

  • 作者单位

    Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, Box 1057,1 Gustave Levy Place, New York, NY 10029, USA;

    Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, Box 1057,1 Gustave Levy Place, New York, NY 10029, USA;

    Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, Box 1057,1 Gustave Levy Place, New York, NY 10029, USA;

    Department of Microbiology, Icahn School of Medicine at Mount Sinai, Box 1054, 1 Gustave Levy Place, New York, NY 10029, USA;

    Cesare Maltoni Cancer Research Centre, Ramazzini Institute, Bentivoglio (Bologna), Italy;

    Cesare Maltoni Cancer Research Centre, Ramazzini Institute, Bentivoglio (Bologna), Italy;

    Cesare Maltoni Cancer Research Centre, Ramazzini Institute, Bentivoglio (Bologna), Italy;

    Cesare Maltoni Cancer Research Centre, Ramazzini Institute, Bentivoglio (Bologna), Italy;

    Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, Box 1057,1 Gustave Levy Place, New York, NY 10029, USA,Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, Box 1057, 1 Gustave Levy Place, New York, NY 10029, USA,Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, Box 1057,1 Gustave Levy Place, New York, NY 10029, USA,Department of Pediatrics, Icahn School of Medicine at Mount Sinai, Box 1057,1 Gustave Levy Place, New York, NY 10029, USA;

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  • 正文语种 eng
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  • 关键词

    Paraben; Triclosan; Mammary Transcriptome and Histology; Breast cancer; Windows of susceptibility;

    机译：对羟基苯甲酸酯;三氯生;乳腺转录组和组织学;乳腺癌;易感性窗口;

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