Altered splenocyte function in aged C57BL/6 mice prenatally exposed to diethylstilbestrol
2005 Study Abstract
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 (DES(prenatal)/DES(adult)) or female(DES) had higher serum levels of interferon-gamma (IFNgamma) in response to administration of an IFNgamma -inducer (soluble proteins-derived from Toxoplasma gondii), compared to female controls, which received oil during prenatal life (Oil(prenatal)/DES(adult)). Splenic lymphocytes from female DES(prenatal)/DES(adult) mice, when activated with Concanavalin A (ConA), also secreted higher levels of IFNgamma compared to female controls (Oil(prenatal)/DES(adult)) when examined at 14-months of age. This increase in IFNgamma 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 DES(prenatal)/DES(adult) had increased expression of the co-stimulatory 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.
- Altered splenocyte function in aged C57BL/6 mice prenatally exposed to diethylstilbestrol, US National Library of Medicine National Institutes of Health, Journal of immunotoxicology, NCBI pubMed PMID: 18958678, 2005 Oct.
- Image credit Global Panorama.