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Mid-gestation Exposure of C57BL/6 Mice to 2,3,7,8-Tetrachlorodibenzo-p-dioxin Causes Postnatal Morphologic Changes in the Spleen and Liver

¹ Department of Biomedical Sciences and Pathobiology, Virginia–Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia
² Edward Via Virginia College of Osteopathic Medicine, Department of Biomedical Sciences, Blacksburg, Virginia

Correspondence: Danielle A. Weinstein, Department of Biomedical Sciences and Pathobiology, Virginia–Maryland Regional College of Veterinary Medicine, Virginia Tech, Duckpond Drive, Blacksburg, VA, 24061-0442, USA; e-mail:dweinste{at}vt.edu.

Pregnant C57BL/6 mice were exposed to 5 µg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or vehicle by oral gavage between gestation days (GDs) 11 and 13. The thymus, spleen, and liver of the pups were examined histologically, and cell surface antigen expression was assessed on postnatal days (PNDs) 1, 14, 25, and 46. In addition to the expected decrease in thymic weight on PND 1, TCDD caused an increase in splenic weight on PND 14 and in hepatic weight on PNDs 14 and 25. The apoptotic index was increased and the corticomedullary border poorly defined in thymuses of TCDD-exposed mice on PND 1, but not at later endpoints. T lymphocytes were increased and B lymphocytes decreased in spleens of the TCDD-exposed mice on PND 46. TCDD-exposed mice had a nearly significant (p =.051) decrease in the number of splenic germinal centers on PND 46. Foci of extramedullary hematopoiesis (EMH) were increased in number in the livers of TCDD-exposed mice on PND 14, suggesting possible increased production of immune cells of unknown phenotype and function in this organ. These results suggest that late-gestation thymic architectural changes caused by TCDD resolve shortly after birth: however, abnormalities in other immunologically important areas may appear later in postnatal life.

Key Words: tetrachlorodibenzo-p-dioxin • gestation • liver • spleen • thymus • TCDD

Abbreviations: AhR, aryl hydrocarbon receptor • Arnt, AhR nuclear translocator • EMH, extramedullary hematopoiesis • FITC, fluorescein isothiocyanate • GCs, germinal centers • GD, gestation day • IACUC, Institutional Animal Care and Use Committee • MHC, major histocompatibility complex • PALS, periarterial lymphoid sheath • PBS, phosphate buffered saline • PCDD, polychorinated dibenzo dioxins • PE, phycoerythrin • PND, postnatal day • TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin • TCR, T cell receptor • Vβ, variable beta

This version was published on July 1, 2008

Toxicologic Pathology, Vol. 36, No. 5, 705-713 (2008)
DOI: 10.1177/0192623308320276


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