Ultrastructure of the cortical epithelium of the rat thymus after in vivo exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known for inducing cortical atrophy in the rat thymus. The present study was conducted to provide ultrastructural evidence for the cortical epithelium to be a target for TCDD in vivo. Juvenile male Wistar rats were orally intubated once with either 50 or 150 micrograms/kg TCDD and killed 4 or 10 days thereafter. Major changes were found in the cortical thymic epithelium. First, a relative shift occurred from "pale" to darker cortical epithelial cell types, as judged by their nuclear and cytoplasmic electron density. This effect was most prominent at 10 days after exposure to 150 micrograms/kg TCDD. The increased electron density of the cortical epithelium indicates an altered state of cellular differentiation. Secondly, at the 150 micrograms/kg dose level focal epithelial cell aggregates were seen both at day 4 and day 10 after administration. This aggregation may either be compound induced or represent a secondary event to the collapse of the thymic stroma. Thirdly, increased vacuolation of cortical epithelial cells was apparent. This effect is interpreted as a consequence rather than a cause of thymocyte depletion from the cortex. This study indicates that TCDD exposure affects the cortical epithelium of the rat thymus at a high dose level. Electron microscopy reveals that the differentiation of epithelial cells is altered. In addition, epithelial cell aggregates are formed.

Repeated dose toxicity and relative potency of 1,2,3,4,6,7-hexachloronaphthalene (PCN 66) 1,2,3,5,6,7-hexachloronaphthalene (PCN 67) compared to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for induction of CYP1A1, CYP1A2 and thymic atrophy in female Harlan Sprague–Dawley rats

“…Histopathologic effects of PCN 66 and 67 in the present study were observed in the liver (hepatocellular hypertrophy, fatty change, necrosis, and inflammation) and thymus (atrophy) and were consistent with effects observed for TCDD (hepatocellular hypertrophy and thymic atrophy) and previous studies of TCDD (De Waal et al 1993). Effects of PCNs on hepatic fatty change, necrosis, and inflammation were not seen with TCDD in the present study.…”

Heterogeneity of epithelial cells in the rat thymus

“…Based on the ultrastructure of the human thymic epithelium, Van De Wijngaert and coworkers (1984) likewise have postulated that morphologically distinct EC subtypes represent sequential stages in a differentiation process. Our recent ultrastructural studies on alterations of the rat thymic epithelium after chemical exposure suggest a similar phenomenon (De Waal et al, 1993b).…”

Morphometric Analysis of the Thymic Epithelial Cell (TEC) Network Using Integrated and Orthogonal Digital Pathology Approaches

“…The cellular component of the cTEC meshwork, also known as "cytoreticulum", is identified in both OTO-SEM and TEM by the characteristic presence of cytoplasmic tonofilaments, vacuoles, and the occasional presence of desmosomes between interconnecting cTEC projections (Fig. S4), as reported [68][69][70][71][72] . These distinguishing epithelial features provide validation of cTEC identity, especially when they are projected in proximity to cTEC nuclei, or when the cytoplasmic projection is shown to bud off the cTEC on the same z-plane (Fig.…”