Changes in mammary histology and transcriptome profiles by low-dose exposure to environmental phenols at critical windows of development.
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.
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.
Kalpana
K
Gopalakrishnan
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.
Susan L
SL
Teitelbaum
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.
Luca
L
Lambertini
Department of Microbiology, Icahn School of Medicine at Mount Sinai, Box 1054, 1 Gustave Levy Place, New York, NY 10029, USA.
James
J
Wetmur
Cesare Maltoni Cancer Research Centre, Ramazzini Institute, Bentivoglio (Bologna), Italy.
Fabiana
F
Manservisi
Cesare Maltoni Cancer Research Centre, Ramazzini Institute, Bentivoglio (Bologna), Italy.
Laura
L
Falcioni
Cesare Maltoni Cancer Research Centre, Ramazzini Institute, Bentivoglio (Bologna), Italy.
Simona
S
Panzacchi
Cesare Maltoni Cancer Research Centre, Ramazzini Institute, Bentivoglio (Bologna), Italy.
Fiorella
F
Belpoggi
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. Electronic address: jia.chen@mssm.edu.
Jia
J
Chen
D000818:Animals; D000891:Anti-Infective Agents, Local / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D020869:Gene Expression Profiling; D008321:Mammary Glands, Animal / Q000033:anatomy & histology / Q000187:drug effects* / Q000254:growth & development; D010226:Parabens / Q000633:toxicity*; D011310:Preservatives, Pharmaceutical / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects; D014260:Triclosan / Q000633:toxicity*
D000891:Anti-Infective Agents, Local; D004785:Environmental Pollutants; D010226:Parabens; D011310:Preservatives, Pharmaceutical; D014260:Triclosan; C015358:methylparaben
Breast cancer; Mammary Transcriptome and Histology; Paraben; Triclosan; Windows of susceptibility