Cutaneous Effects of In Utero and Lactational Exposure of C57BL/6J Mice to 2,3,7,8-Tetrachlorodibenzo-<i>p</i>-dioxin
To determine the cutaneous effects of in utero and lactational exposure to the AHR ligand 2,3,7,8-tetrachlorodibenzo-<i>p</i>-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 func...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Toxics |
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| Online Access: | https://www.mdpi.com/2305-6304/9/8/192 |
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| author | Jyoti Bhuju Kristin M. Olesen Clarisse S. Muenyi Tejesh S. Patel Robert W. Read Lauren Thompson Omar Skalli Qi Zheng Elizabeth A. Grice Carrie Hayes Sutter Thomas R. Sutter |
| author_facet | Jyoti Bhuju Kristin M. Olesen Clarisse S. Muenyi Tejesh S. Patel Robert W. Read Lauren Thompson Omar Skalli Qi Zheng Elizabeth A. Grice Carrie Hayes Sutter Thomas R. Sutter |
| author_sort | Jyoti Bhuju |
| collection | DOAJ |
| description | To determine the cutaneous effects of in utero and lactational exposure to the AHR ligand 2,3,7,8-tetrachlorodibenzo-<i>p</i>-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. |
| first_indexed | 2024-03-10T08:19:59Z |
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| id | doaj.art-d79d007466db47fd9f5b17e03a39b4ec |
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| issn | 2305-6304 |
| language | English |
| last_indexed | 2024-03-10T08:19:59Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxics |
| spelling | doaj.art-d79d007466db47fd9f5b17e03a39b4ec2023-11-22T10:03:47ZengMDPI AGToxics2305-63042021-08-019819210.3390/toxics9080192Cutaneous Effects of In Utero and Lactational Exposure of C57BL/6J Mice to 2,3,7,8-Tetrachlorodibenzo-<i>p</i>-dioxinJyoti Bhuju0Kristin M. Olesen1Clarisse S. Muenyi2Tejesh S. Patel3Robert W. Read4Lauren Thompson5Omar Skalli6Qi Zheng7Elizabeth A. Grice8Carrie Hayes Sutter9Thomas R. Sutter10Department of Biological Sciences, University of Memphis, Memphis, TN 38152, USADepartment of Biological Sciences, University of Memphis, Memphis, TN 38152, USADepartment of Surgery, University of Tennessee Health Sciences Center, Memphis, TN 38104, USAKaplan-Amonette Department of Dermatology, University of Tennessee Health Sciences Center, Memphis, TN 38104, USADepartment of Biological Sciences, University of Memphis, Memphis, TN 38152, USAIntegrated Microscopy Center, University of Memphis, Memphis, TN 38152, USADepartment of Biological Sciences, University of Memphis, Memphis, TN 38152, USADepartment of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Biological Sciences, University of Memphis, Memphis, TN 38152, USADepartment of Biological Sciences, University of Memphis, Memphis, TN 38152, USATo determine the cutaneous effects of in utero and lactational exposure to the AHR ligand 2,3,7,8-tetrachlorodibenzo-<i>p</i>-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.https://www.mdpi.com/2305-6304/9/8/192TCDD: 2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxindioxinAHR: aryl hydrocarbon receptorskinepidermisatopic dermatitis |
| spellingShingle | Jyoti Bhuju Kristin M. Olesen Clarisse S. Muenyi Tejesh S. Patel Robert W. Read Lauren Thompson Omar Skalli Qi Zheng Elizabeth A. Grice Carrie Hayes Sutter Thomas R. Sutter Cutaneous Effects of In Utero and Lactational Exposure of C57BL/6J Mice to 2,3,7,8-Tetrachlorodibenzo-<i>p</i>-dioxin Toxics TCDD: 2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin dioxin AHR: aryl hydrocarbon receptor skin epidermis atopic dermatitis |
| title | Cutaneous Effects of In Utero and Lactational Exposure of C57BL/6J Mice to 2,3,7,8-Tetrachlorodibenzo-<i>p</i>-dioxin |
| title_full | Cutaneous Effects of In Utero and Lactational Exposure of C57BL/6J Mice to 2,3,7,8-Tetrachlorodibenzo-<i>p</i>-dioxin |
| title_fullStr | Cutaneous Effects of In Utero and Lactational Exposure of C57BL/6J Mice to 2,3,7,8-Tetrachlorodibenzo-<i>p</i>-dioxin |
| title_full_unstemmed | Cutaneous Effects of In Utero and Lactational Exposure of C57BL/6J Mice to 2,3,7,8-Tetrachlorodibenzo-<i>p</i>-dioxin |
| title_short | Cutaneous Effects of In Utero and Lactational Exposure of C57BL/6J Mice to 2,3,7,8-Tetrachlorodibenzo-<i>p</i>-dioxin |
| title_sort | cutaneous effects of in utero and lactational exposure of c57bl 6j mice to 2 3 7 8 tetrachlorodibenzo i p i dioxin |
| topic | TCDD: 2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin dioxin AHR: aryl hydrocarbon receptor skin epidermis atopic dermatitis |
| url | https://www.mdpi.com/2305-6304/9/8/192 |
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