Cutaneous Effects of In Utero and Lactational Exposure of C57BL/6J Mice to 2,3,7,8-Tetrachlorodibenzo-p-dioxin.

Jyoti Bhuju,Kristin M Olesen,Tejesh S Patel,Thomas R Sutter,Elizabeth A Grice,Carrie Hayes Sutter,Qi Zheng,Omar Skalli,Lauren Thompson,Robert W Read,Clarisse S Muenyi

doi:10.3390/toxics9080192

Jyoti Bhuju, Kristin M Olesen + Show 9 more

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https://doi.org/10.3390/toxics9080192

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Abstract

To determine the cutaneous effects of in utero and lactational exposure to the AHR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), pregnant C57BL/6J mice were exposed by gavage to a vehicle or 5 μg TCDD/kg body weight at embryonic day 12 and epidermal barrier formation and function were studied in their offspring from postnatal day 1 (P1) through adulthood. TCDD-exposed pups were born with acanthosis. This effect was AHR-dependent and subsided by P6 with no evidence of subsequent inflammatory dermatitis. The challenge of adult mice with MC903 showed similar inflammatory responses in control and treated animals, indicating no long-term immunosuppression to this chemical. Chloracne-like sebaceous gland hypoplasia and cyst formation were observed in TCDD-exposed P21 mice, with concomitant microbiome dysbiosis. These effects were reversed by P35. CYP1A1 and CYP1B1 expression in the skin was increased in the exposed mice until P21, then declined. Both CYP proteins co-localized with LRIG1-expressing progenitor cells at the infundibulum. CYP1B1 protein also co-localized with a second stem cell niche in the isthmus. These results indicate that this exposure to TCDD causes a chloracne-like effect without inflammation. Transient activation of the AhR, due to the shorter half-life of TCDD in mice, likely contributes to the reversibility of these effects.

Highlights

Early-life exposures to environmental pollutants can impact development and lead to pathologies later in life, such as obesity, diabetes, cardiovascular, neurological, and reproductive dysfunction [1,2,3,4]
Common persistent organic pollutants (POPs) include dioxins and halogenated dioxin-like compounds (DLCs) that are produced during industrial processes, including manufacturing of herbicides and pesticides, incineration, and bleaching of pulp and papers. 2,3,7,8Tetrachlorodibenzo-p-dioxin (TCDD) is the prototypical and most potent compound in the family of DLCs [6] and mediates its toxic effects through the activation of the aryl hydrocarbon receptor (AHR) [7]
Time-mated wild type and AhR null mice were treated by gavage with TCDD at E12 or E13 and sacrificed at E15 or E16 when an X-gal dye exclusion assay was performed on the fetuses

Summary

Introduction

Early-life exposures to environmental pollutants can impact development and lead to pathologies later in life, such as obesity, diabetes, cardiovascular, neurological, and reproductive dysfunction [1,2,3,4]. Persistent organic pollutants (POPs) that are extremely resistant to degradation bioaccumulate in animals and humans, causing long-term toxic effects [5]. Common POPs include dioxins and halogenated dioxin-like compounds (DLCs) that are produced during industrial processes, including manufacturing of herbicides and pesticides, incineration, and bleaching of pulp and papers. 2,3,7,8Tetrachlorodibenzo-p-dioxin (TCDD) is the prototypical and most potent compound in the family of DLCs [6] and mediates its toxic effects through the activation of the aryl hydrocarbon receptor (AHR) [7]. The most significant clinical cutaneous effect of TCDD toxicity in humans is the skin condition called chloracne that develops within days following intensive exposures [11] Because dioxins accumulate in fat tissue due to their lipophilic nature, breast milk is an additional and significant source of exposure for breastfed newborns [9,10].

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