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Published January 2015 | public
Journal Article Open

Dioxin Exposure Blocks Lactation Through a Direct Effect on Mammary Epithelial Cells Mediated by the Aryl Hydrocarbon Receptor Repressor


In mammals, lactation is a rich source of nutrients and antibodies for newborn animals. However, millions of mothers each year experience an inability to breastfeed. Exposure to several environmental toxicants, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), has been strongly implicated in impaired mammary differentiation and lactation. TCDD and related polyhalogenated aromatic hydrocarbons are widespread industrial pollutants that activate the aryl hydrocarbon receptor (AHR). Despite many epidemiological and animal studies, the molecular mechanism through which AHR signaling blocks lactation remains unclear. We employed in vitro models of mammary differentiation to recapitulate lactogenesis in the presence of toxicants. We demonstrate AHR agonists directly block milk production in isolated mammary epithelial cells. Moreover, we define a novel role for the aryl hydrocarbon receptor repressor (AHRR) in mediating this response. Our mechanistic studies suggest AHRR is sufficient to block transcription of the milk gene β-casein. Since TCDD is a prevalent environmental pollutant that affects women worldwide, our results have important public health implications for newborn nutrition.

Additional Information

© 2014 The Author. Published by Oxford University Press on behalf of the Society of Toxicology. Received April 4, 2014. Revision received September 5, 2014. Accepted September 23, 2014. First published online: September 29, 2014. We thank Drs James Bear (University of North Carolina, Chapel Hill, NC) and Thomas Marshall (University of Utah, Salt Lake City, UT) for providing the pLentiLox5.0-GFP vector; Dr Mark Hahn (Woods Hole Oceanographic Institution, Woods Hole, MA) for providing pcDNA-mAhRR, and Dr Oliver Hankinson (University of California, Los Angeles, CA) for providing pACTAG-HA-AHR and pACTAG-HA-ARNT. The authors declare that they have no conflicts of interest. The National Institutes of Health [R01-CA143815, R01-CA140296, R01-GM090082]; the Department of Defense Breast Cancer Research Program [W81XWH-09-01-04310]; the National Institutes of Health Development Biology Training Grant [5T32 HD07491 to K.J.B.].

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August 20, 2023
August 20, 2023