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

Hubble Space Telescope Observations of Field Ultracool Dwarfs at High Galactic Latitude

We present a sample of 17 newly discovered ultracool dwarf candidates later than ~M8, drawn from 231.90 arcmin2 of {\it Hubble Space Telescope} Wide Field Camera 3 infrared imaging. By comparing the observed number counts for 17.5<J_125<25.5 AB mag to an exponential disk model, we estimate a vertical scale height of z_scl=290 +- 25 (random) +- 30 (systematic) pc for a binarity fraction of f_b=0. While our estimate is roughly consistent with published results, we suggest that the differences can be attributed to sample properties, with the present sample containing far more substellar objects than previous work. We predict the object counts should peak at J_{125}~24 AB mag due to the exponentially-declining number density at the edge of the disc. We conclude by arguing that trend in scale height with spectral type may breakdown for brown dwarfs since they do not settle onto the main sequence.Comment: 9 pages, 6 figures, 3 tables, accepted to ApJ (v2 is consistent with Referee changes