Subcutaneous 21-day Administration of 17alpha-ethinyl estradiol or 17beta-estradiol alters the thymus of 8-week-old C57BL/6 Mice (B217)

Abstract

Abstract Exposure to exogenous estrogens occurs via multiple sources (i.e. environmental contamination, contraceptives). Presently, little data exist regarding the immune effects of the synthetic estrogen 17α-ethinyl estradiol (EE) and its relative potency compared to 17β-estradiol (E2). In this study, we investigated the immune effects of daily subcutaneous injections of either EE or E2 on intact juvenile male and female C57BL/6 mice for 21 days with concentrations of 0.04 μg/25 g BW, 0.4 μg/25 g BW, or 4.0 μg/25 g BW. In male mice, thymus weight and thymus to BW ratio were significantly decreased at 4.0 EE dose, whereas in female mice significant decreases were noticed at 0.4 and 4.0 doses of both E2 and EE. Thymocyte absolute numbers were significantly diminished at both 4.0 E2 and EE dosing levels in males, and decreased at the 0.4 and 4.0 doses of E2 and EE in females. Decreasing trends in CD4+/CD8+ expression were observed in EE-treated mice, reaching significance at 4.0 EE in the females. The male spleen NK 1.1 cell surface marker was significantly increased at 0.04 and 4.0 EE treatments, as well as at 0.4 E2. In summary, results of these data suggest that a 21-day subcutaneous exposure of either E2 or EE is sufficient to significantly alter thymic endpoints. With the exception of the NK 1.1 subset, splenic endpoints did not yield any remarkable results. These findings suggest that the thymus is a more sensitive target than the spleen with regard to subacute exposure of 17α-ethinyl estradiol.