TY - JOUR
T1 - Changes in mammary histology and transcriptome profiles by low-dose exposure to environmental phenols at critical windows of development
AU - Gopalakrishnan, Kalpana
AU - Teitelbaum, Susan L.
AU - Lambertini, Luca
AU - Wetmur, James
AU - Manservisi, Fabiana
AU - Falcioni, Laura
AU - Panzacchi, Simona
AU - Belpoggi, Fiorella
AU - Chen, Jia
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Mammary Transcriptome and Histology
KW - Paraben
KW - Triclosan
KW - Windows of susceptibility
UR - http://www.scopus.com/inward/record.url?scp=84993949277&partnerID=8YFLogxK
U2 - 10.1016/j.envres.2016.10.021
DO - 10.1016/j.envres.2016.10.021
M3 - Article
C2 - 27810681
AN - SCOPUS:84993949277
SN - 0013-9351
VL - 152
SP - 233
EP - 243
JO - Environmental Research
JF - Environmental Research
ER -