Electronic Theses and Dissertations Archive

Date

2026

Document Type

Thesis

Degree Name

Master of Science

Department

Biology

Committee Chair

Thomas Sutter

Committee Member

Carrie Sutter

Committee Member

Omar Skalli

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known to induce chloracne, a skin condition that presents with acanthosis, hyperkeratosis, comedones, and sebaceous gland (SG) involution. While studies have reported chloracne-like phenotypes in mice including seboatrophy, the mechanisms leading to chloracne are not well understood. Recent studies highlight the co-localization of TCDD-mediated CYP1A1 induction with LRIG1+ progenitor cells of the hair follicle, indicating that TCDD may target specific cells to elicit seboatrophy. To explore these effects of TCDD, we analyzed single-cell RNA expression in wild-type and Ahr-null mice. In utero and lactationally exposed mouse skin at P21 showed prominent Ahr-dependent seboatrophy, with induction of Blimp1, a transcriptional repressor known to regulate gland size. TCDD preferentially induced the AHR biomarkers, Cyp1a1 and Cyp1b1, in the lower infundibulum near the junctional zone where LRIG1+ stem cells reside, consistent with reports of protein induction. A second region of Cyp1a1 induction was the SG, where Cyp1a1 was markedly elevated in both less differentiated sebocytes and the basal proliferating cells. A 3-day topical study was performed to investigate early effects of TCDD exposure. A dose-dependent increase of Cyp1a1 expression was observed in the more differentiated cells of the SG. Scd1 area expansion, and elevated Nile Red lipid staining identified increased sebocyte differentiation and lipid production as early responses to TCDD. Increased numbers of sebocytes expressing high levels of Blimp1 further supported this TCDD effect on SG differentiation. Together these findings provide strong evidence that TCDD enhanced SG differentiation in vivo. This effect preceded Ahr-dependent seboatrophy and provided a framework for understanding how TCDD affects the dynamics of the pilosebaceous unit.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to ProQuest/Clarivate.

Notes

Embargoed until 07-20-2027

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Available for download on Tuesday, July 20, 2027

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