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.