Estradiol and Atrazine induce apoptosis and regression of the thymus gland in Xenopus laevis embryos and tadpoles


Meeting Abstract

P1.68  Saturday, Jan. 4 15:30  Estradiol and Atrazine induce apoptosis and regression of the thymus gland in Xenopus laevis embryos and tadpoles. QUINDE, J*; MORANTE, K; BAYNHEM, H; MCCAFFREY, A; GARCIA, J; PRIYAMVADA, L; HECKMAN, K; TEMKIN, M; SCHREIBER, A.M.; St. Lawrence University, NY; St. Lawrence University, NY; St. Lawrence University, NY; St. Lawrence University, NY; St. Lawrence University, NY; St. Lawrence University, NY; St. Lawrence University, NY; St. Lawrence University, NY; St. Lawrence University, NY aschreiber@stlawu.edu

High levels of endogenously-produced or exogenously-administered estradiol are known to cause the thymus to atrophy in mammals, similar to the suppressive effects of glucocorticoids on the immune system. However, the influence of estradiol and estrogenic compounds on thymus gland development in tadpoles and other aquatic vertebrates remains unknown. Here we show that treatment of embryos (2 days post-fertilization, dpf) and young tadpoles (7 dpf; Nieuwkoop and Faber stage 50) for 4 or 6 days, respectively, with estradiol (10 uM) significantly reduces thymus gland size by approximately 35%. Treatment of tadpoles with estradiol induces maximum active caspase-3 expression (a mediator of programmed cell death) in thymocytes within 48-72 hours, after which levels of thymus cell apoptosis decrease. Treatment of NF stage 50 tadpoles with atrazine (100 ug/L) for 7 days reduced thymus size by 35%. Atrazine is a widely-used herbicide that is also known to disrupt vertebrate estrogen signaling by increasing endogenous estradiol synthesis by activating p450 aromatase. In contrast, treatment of either embryos or NF stage 50 tadpoles for 7-14 days with bisphenol A (BPA, 5-15 uM) had no effect on thymus size. BPA is a common constituent of plastics that has also been reported to function as a weak estrogen receptor agonist. Ongoing experiments using estrogen and glucocorticoid receptor antagonists (fulvestrant and RU-486, respectively) are being conducted to determine if atrazine-induced thymus regression is mediated entirely by the estrogen receptor, or if atrazine also induces thymus regression via stimulating the production of glucocorticoids.

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