Altered splenocyte function in aged C57BL/6 mice prenatally exposed to diethylstilbestrol.
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.
Fenaux
Jillian B
JB
Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, Virginia Maryland Regional College of Veterinary Medicine, Virginia Tech (Virginia Polytechnic Institute and State University), Blacksburg, Virginia, USA.
Gogal
Robert M
RM
Lindsay
David
D
Hardy
Carrie
C
Ward
Daniel L
DL
Saunders
Geoffrey
G
Ahmed
S Ansar
SA