Toxicological Sciences 68, 465-472 (2002)
Copyright © 2002 by the Society of Toxicology
REPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY |
In Utero Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin Causes Accelerated Terminal Differentiation in Fetal Mouse Skin
,1
* Molecular and Environmental Toxicology Center and
School of Pharmacy, University of Wisconsin, Madison, Madison, Wisconsin 53706;
Department of Pathology, University of Wisconsin Medical School, Madison, Wisconsin 53706
2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD), a ubiquitous environmental toxin, has been shown to cause a human skin pathology called chloracne. The majority of laboratory mouse strains, with the exception of mice bearing a mutation in thehairless gene, fail to display overt signs of chloracne upon exposure to TCDD. As a result, only minimal data exist on the effects of TCDD in adult haired mice and no data exist on the effects of TCDD in developing mouse skin. Here we report that TCDD affects the temporal expression of protein markers of keratinocyte terminal differentiation during murine skin morphogenesis. Immunohistochemical analysis of E16 mice reveals accelerated expression of the intermediate filament-associated protein filaggrin in response to TCDD. At a later developmental time and after birth, expression of filaggrin and loricrin is indistinguishable between treatment and control groups. At E16 expression of keratins 5, 6, and 10 are unaltered in TCDD-exposed individuals and TUNEL analysis shows no apoptotic cells in the basal and spinous layers of either treatment or control groups. At E16, immunohistochemical analysis of AhR-null mouse skin reveals accelerated filaggrin expression in both vehicle and TCDD exposed animals. We therefore hypothesize that AhR acts as a modulator of late stage keratinocyte terminal differentiation.
Key Words: TCDD; skin; AhR; filaggrin; mouse.
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