Abstract
Endocrine disrupting chemicals (EDCs) with estrogenic activity are ubiquitous in the environment. Studies of select EDCs have suggested that human exposure alters the immune system leading to increases in infection and autoimmune disease frequency. How these alterations occur is unclear. Exogenous and pregnancy-related increases in estrogen have been shown to induce atrophy and alterations in thymocyte development, suggesting a potential mechanism for EDC alteration of the immune system. Diethylstilbestrol (DES), a synthetic estrogen once prescribed to pregnant women, and HPTE, the metabolite of the once widely applied pesticide Methoxychlor (a replacement for DDT) are EDCs of interest. Using an in vitro assay, our research probed whether HPTE and DES alter thymocyte development in embryonic C57Bl/6 mice and at what concentrations. We also examined the mechanism by which DES and HPTE affect thymocyte differentiation. Our preliminary data show a dose-dependent decrease in thymocyte viability and alterations in thymocyte population distribution. Over the range of doses tested, increasing DES and HPTE concentration led to significant decreases in CD4+ intermediate and DP T-cells. Furthermore, we designed a time course experiment to probe the cell death mechanism induced by DES and HPTE using Annexin V and PI staining. Our work suggests that one mechanism of action of DES and HPTE on embryonic thymocytes is induction of cell death through apoptosis.