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Research Article Advance Publication

Environ Health Perspect; DOI:10.1289/ehp.1308045

Effects of in Utero Exposure of C57BL/6J Mice to 2,3,7,8-Tetrachlorodibenzo-p-dioxin on Epidermal Permeability Barrier Development and Function

Clarisse S. Muenyi,1 Sandra Leon Carrion,1 Lynn A. Jones,1 Lawrence H. Kennedy,2 Andrzej T. Slominski,3 Carrie H. Sutter,1 and Thomas R. Sutter1,2
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1Department of Biological Sciences, 2Department of Chemistry, University of Memphis, Memphis, Tennessee, USA; 3Department of Pathology, University of Tennessee Health Science Center, Memphis, Tennessee, USA
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This EHP Advance Publication article has been peer-reviewed, revised, and accepted for publication. EHP Advance Publication articles are completely citable using the DOI number assigned to the article. This document will be replaced with the copyedited and formatted version as soon as it is available. Through the DOI number used in the citation, you will be able to access this document at each stage of the publication process.

Citation: Muenyi CS, Carrion SL, Jones LA, Kennedy LH, Slominski AT, Sutter CH, Sutter TR. Effects of in Utero Exposure of C57BL/6J Mice to 2,3,7,8-Tetrachlorodibenzo-p-dioxin on Epidermal Permeability Barrier Development and Function. Environ Health Perspect;

Received: 20 December 2013
Accepted: 4 June 2014
Advance Publication: 6 June 2014

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Background: Development of the epidermal permeability barrier (EPB) is essential for neonatal life. Defects in this barrier are found in many skin diseases such as atopic dermatitis.

Objective: We investigated the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the development and function of the EPB.

Methods: Timed pregnant C57BL/6J mice were gavaged with corn oil or TCDD (10 µg/kg body weight) on gestation day 12. Embryos were harvested on embryonic days 15 (E15), E16, E17 and postnatal day 1 (PND1).

Results: A skin permeability assay showed that TCDD accelerated the development of the EPB, beginning at E15. This was accompanied by a significant decrease in transepidermal water loss (TEWL), enhanced stratification and formation of the stratum corneum (SC). The levels of several ceramides were significantly increased at E15 and E16. PND1 histology revealed TCDD-induced acanthosis and epidermal hyperkeratosis. This was accompanied by disrupted epidermal tight junction (TJ) function, increasing dye leakage at the terminal claudin-1 staining TJs of the stratum granulosum. As these animals did not have enhanced rates of TEWL, a commonly observed phenotype in animals with TJ defects, we performed tape-stripping. Removal of most of the SC resulted in a significant increase in TEWL in TCDD-exposed PND1 pups compared with their control group.

Conclusions: These findings demonstrate that in utero exposure to TCDD accelerates the formation of an abnormal EPB with leaky TJs, warranting further study of environmental exposures, epithelial tight junction integrity and atopic disease.

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