Induction of apoptosis in murine fetal thymocytes following perinatal exposure to diethylstilbestrol

International Journal of Toxicology
Nicole BrownPrakash S Nagarkatti

Abstract

Perinatal exposure to diethylstilbestrol (DES) is known to cause thymic atrophy in mice, although the precise mechanism remains unclear. In the current study the authors investigated whether perinatal exposure to DES would trigger apoptosis in thymocytes. To this end, C57BL/6 pregnant mice were injected intraperitoneally (i.p.) on gestational day (gd)-15 and -16 with 5 microg/kg DES. Analysis of thymi harvested from mice on gd-17, gd-19 and postnatal day (PD)-1, showed a significant reduction in thymic cellularity on gd-17 only. Additionally, DES treatment significantly altered the proportion and absolute number of T-cell subsets, particularly on gd-17. Apoptosis was increased in DES-treated thymocytes when compared to the controls and was seen only on gd-17. Moreover, DES-treated gd-17 thymocytes had increased Asp-Glu-Val-Asp (DEVDase) activity. Microarray analysis of 96 apoptotic genes in gd-17 thymocytes revealed that exposure to DES increased the expression of several apoptotic genes primarily belonging to tumor necrosis factor (TNF) and TNF receptor (TNFR) family. Taken together, these results suggest that DES-induced thymic atrophy following perinatal exposure may result, at least in part, from increased apoptosis mediate...Continue Reading

References

Aug 26, 1993·Nature·J OgasawaraS Nagata
May 15, 1995·Annals of Internal Medicine·R M GiustiE E Hatch
Jan 1, 1995·Advances in Immunology·P Kisielow, H von Boehmer
Nov 1, 1993·Cellular Immunology·S D HolladayM I Luster
Feb 1, 1997·Toxicology and Applied Pharmacology·A B KamathM Nagarkatti
Jun 6, 1998·The Journal of Experimental Medicine·H KishimotoJ Sprent
Jun 25, 1998·Current Opinion in Immunology·T Saito
Aug 15, 1998·Critical Reviews in Immunology·T Saito, N Watanabe
Jun 8, 1999·Annual Review of Immunology·E SebzdaP S Ohashi
Jun 29, 1999·Cellular Immunology·K KurasawaI Iwamoto
Nov 9, 2000·The Journal of Steroid Biochemistry and Molecular Biology·G MorF Naftolin
Oct 20, 2001·American Journal of Reproductive Immunology : AJRI·G MorF Kohen
Oct 22, 2002·Toxicological Sciences : an Official Journal of the Society of Toxicology·Yoonkyung DoPrakash S Nagarkatti
May 27, 2003·Nature Reviews. Immunology·Ed Palmer
Jan 14, 2004·Toxicological Sciences : an Official Journal of the Society of Toxicology·Iris A CamachoPrakash S Nagarkatti
Jan 14, 2004·Toxicological Sciences : an Official Journal of the Society of Toxicology·Michael T FisherPrakash S Nagarkatti

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis