Diethylstilbestrol exposure during fetal development affects thymus: studies in fourteen-month-old mice

Abstract

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 μg; DES prenatal) or vehicle oil (Oil; Oil prenatal). One-year after birth, these mice were given a single dose of DES (DES adult) and thymii of these mice were studied two months later. DES prenatal/DES adult female mice had a significant decrease in thymocyte cellularity compared to female controls (Oil prenatal/DES adult). In contrast, male DES prenatal/DES adult 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 DES prenatal/DES adult mice compared to their sex-matched controls. Nevertheless, thymocytes cultured in media alone showed increased percentage of apoptosis in CD4 +CD8 + subset from female DES prenatal/DES adult mice compared to similar cultures from sex-matched controls. Interestingly, the percentage of apoptosis of CD4 +CD8 + thymocytes in media-only cultures from DES prenatal/DES adult female mice was comparable to in vitro dexamethasone-exposed cultures from Oil prenatal/DES adult female mice. This pattern of increased apoptosis of female CD4 +CD8 + subset was not noticed in male DES prenatal/DES adult 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.