Altered splenocyte function in aged C57BL/6 mice prenatally exposed to diethylstilbestrol

Julian B. Fenaux, Robert M. Gogal, David Lindsay, Carrie Hardy, Daniel L. Ward, Geoffrey Saunders, S. Ansar Ahmed

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1 Scopus citations


The linkage between in utero exposure to diethylstilbestrol (DES) and the manifestation of a variety of reproductive disorders and possibly immune alterations in adults (i.e., human and mice) is suggestive of a fetal basis of adult disease. While the long-term adverse consequences of prenatal DES-exposure on reproductive disorders are well known, there is a paucity of data with regard to immune outcome. We hypothesize that prenatal DES-exposure "imprints" the immune system, altering the response to subsequent exposure to DES in adult mice. In this pilot study, C57BL/6 mice were prenatally exposed to DES or vehicle only (oil) and then exposed to DES at 1 year of age. Potential alterations in the spleen were then examined. Female DES-exposed mice (DESprenatal/DESadult) or femaleDES had higher serum levels of interferon-gamma (IFNy) in response to administration of an IFNγ-inducer (soluble proteins-derived from Toxoplasma gondii), compared to female controls, which received oil during prenatal life (Oil prenatal/DESadult). Splenic lymphocytes from female DESprenatal/DESadult mice, when activated with Concanavalin A (ConA), also secreted higher levels of IFNγ compared to female controls (Oilprenatal/DESadult) when examined at 14-months of age. This increase in IFNγ in prenatal DES-exposed mice is not due to enhanced numbers of splenocytes or increased relative percentages of CD4+ or CD8+ cells. ConA-activated T-cells from female DESprenatal/DESadult had increased expression of the costimulatory molecule, CD28. These above immune changes were not evident in the males prenatally exposed to DES. Prenatal DES exposure also did not induce autoimmunity in non-autoimmune C57BL/6 mice. Overall, results from these prefatory studies suggest that prenatal DES exposure may have long-term immune alterations, which become evident following a secondary exposure to DES in adult life.

Original languageEnglish (US)
Pages (from-to)221-229
Number of pages9
JournalJournal of Immunotoxicology
Issue number4
StatePublished - Oct 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology
  • Toxicology


  • Diethylstilbestrol (DES)
  • Gender
  • Interferon-gamma (IFNγ)
  • Prenatal
  • Splenocytes


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