Diethylstilbestrol exposure during fetal development affects thymus: studies in fourteen-month-old mice.
In utero exposure to diethylstilbestrol (DES) may have long-term immunological alterations after birth. It is hypothesized that in utero exposure to DES may pre-program the thymus to result in aberrant response to a subsequent adult exposure to an endocrine disrupting chemical. Pregnant mice at 14-days gestation were given either DES (0.25 microg; DESprenatal) or vehicle oil (Oil; Oil(prenatal)). One-year after birth, these mice were given a single dose of DES (DESadult) and thymii of these mice were studied two months later. DESprenatal/DESadult female mice had a significant decrease in thymocyte cellularity compared to female controls (Oil(prenatal)/DESadult). In contrast, male DESprenatal/DESadult mice had increased thymic mass and a trend towards increased thymocyte cellularity. There were no significant differences in the relative percentages of major thymocyte subsets, CD4-CD8-, CD4+CD8+, CD4+CD8-, CD4-CD8+, in either female or male DESprenatal/DESadult mice compared to their sex-matched controls. Nevertheless, thymocytes cultured in media alone showed increased percentage of apoptosis in CD4+CD8+ subset from female DESprenatal/DESadult mice compared to similar cultures from sex-matched controls. Interestingly, the percentage of apoptosis of CD4+CD8+ thymocytes in media-only cultures from DESprenatal/DESadult female mice was comparable to in vitro dexamethasone-exposed cultures from Oil(prenatal)/DESadult female mice. This pattern of increased apoptosis of female CD4+CD8+ subset was not noticed in male DESprenatal/DESadult mice. This implies that prenatal DES exposure in female mice intrinsically alters the degree of apoptosis in CD4+CD8+ thymocyte subset. Together, these data imply that prenatal DES exposure induces long-term thymic changes in a sex-related fashion.
Fenaux
J B
JB
Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathobiology, Virginia Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060-0342, USA.
Gogal
R M
RM
Ahmed
S Ansar
SA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004054:Diethylstilbestrol / Q000008:administration & dosage*; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage*; D005260:Female; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012737:Sex Factors; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000196:embryology / Q000503:physiopathology*
D004968:Estrogens, Non-Steroidal; D004054:Diethylstilbestrol