Estrogens have the ability to alter the immune system. Diethylstilbestrol (DES), asynthetic estrogen, is known to have estrogenic activity and induce thymic alterations.We investigated the mechanism by which DES is able to alter T cells and thus theimmune system. First, we studied the effect of DES on mature T cells by using the T cellleukemia cell line, Jurkat. We found that DES treatment reduced cell viability andincreased apoptosis. Additionally, apoptosis was found to involve both death receptorand mitochondria1 pathways. Furthermore, estrogen receptor beta was found to beexpressed in these cells and increased following DES treatment. Secondly, we studiedthe effect of DES on developing T cells using two different mouse models, timed pregnant and HY-TCR transgenic. The pregnant mouse model showed that DESexposure in utero reduced thymic cell viability and induced apoptosis at gestational day(gd)-17. Apoptosis was found to involve the death receptor pathway. Additionally,alterations in T cell subsets was most pronounced at gd-17 as well. The HY-TCR tgmouse model showed that DES exposure altered both positive and negative selection of Tcells. Furthermore, DES was found to alter the ability of T cells to proliferate during animmune response. Finally, we studied the intrathymic interaction between thymicstromal cells and thymic T cells. We found that cel1:cell interaction was important forinducing T cell apoptosis in the thymus. Additionally, FasL expression was increased onthymic stromal cells following DES exposure. Furthermore, the presence of both FasL onstromal cells and Fas on T cells was important for inducing T cell apoptosis in thethymus.

Muitas substâncias descartadas no meio ambiente não são totalmente degradadas, podendo assim persistir no ambiente. Diversos compostos são continuamente introduzidos no ambiente podendo afetar a biota e inclusive o homem. Os fármacos são alguns desses compostos que depois de descartados podem chegar nos corpos de águas naturais, e dentre eles merecem especial atenção os hormônios sintéticos utilizados em larga escala por mulheres em todo o mundo, na forma de contraceptivos orais. O hormônio sintético 17α-etinilestradiol é um micropoluente no ambiente aquático, que pode causar distúrbios na reprodução de diversos organismos atuando como um desregulador endócrino. O presente estudo teve como objetivo principal analisar o efeito do hormônio sintético 17α-etinilestradiol sobre o cladócero Daphnia magna, por meio de testes ecotoxicológicos. Testes de toxicidade crônica foram realizados em duas gerações consecutivas deste microcrustáceo (F0 e F1). Para os testes utilizaram-se neonatas com menos de 24 horas de idade, 6 concentrações do hormônio e dois controles. Foram estabelecidas 10 réplicas com 1 indivíduo por réplica. O ensaio foi realizado em incubadora com temperatura de 25 ± 1°C e fotoperíodo de 12h claro:12h escuro, com duração de 11 (F0) e 13 dias (F1), com término coincidindo com o nascimento das neonatas da terceira ninhada no controle. Os resultados evidenciaram que a exposição ao hormônio diminuiu a fecundidade de Daphnia magna nas quatro maiores concentrações de etinilestradiol na F0 e na concentração de 1000 μg L-1 da F1, revelando maior resistência ao contaminante na segunda geração. Na maior concentração do composto, o tempo para a produção das duas primeiras ninhadas foi maior na geração F1, quando comparada ao controle. Na concentração de 250 μg L-1 verificou-se a ocorrência de um indivíduo intersexo, apresentando tanto características de macho como de fêmea. Os resultados deste estudo evidenciaram que o 17α-etinilestradiol afeta a reprodução de Daphnia magna, e que também pode afetar a reprodução de diferentes invertebrados aquáticos, o que, a longo prazo pode causar danos às populações e comunidades aquáticas, diminuindo as populações e podendo até extingui-las eventualmente. / Many substances are discarded in the environment and not completely degraded, thus persisting in the environment. Some of these are continuously introduced in the environment, affecting the biota, including man. Pharmaceutical drugs are some of these compounds that after discarded can occur in natural water bodies and among them the synthetic hormones deserve special attention for being used in large scale by women world widely, as oral contraceptives. The synthetic hormone 17α-ethinyl estradiol is therefore a micropoluent in the aquatic environment, i. e. found in low concentrations that can cause deleterious effects in the reproduction of many organisms, acting as an endocrine disruptor. The present study had as main objective to analyze the effect of the synthetic estrogen 17α-ethinyl estradiol on the cladoceran Daphnia magna, by carrying out ecotoxicological tests. Chronic toxicity tests were performed on two consecutive generations of this microcrustacean (F0 and F1). In order to perform the tests, neonates aged less than 24 hours, 6 hormones concentrations and two types of controls were used. Ten replicates were established with one individual each. The test was performed in a growth chamber at the constant temperature of 25 ± 1°C and 12 h light:12 h dark photoperiod, had the duration of 11 and 13 days for the F1 and F0 generations, respectively, coinciding with the birth of the third brood in the control. The results evidenced that the exposition to the hormone decreased D. magna fecundity in the four highest of ethinyl estradiol in F0, and in the concentration 1000 μg L-1 for the F1, indicating resistance increase in the second generation. In the highest concentration of this compound the time for the production of the first two broods were higher in the F1 generation as compared with the controls. In the hormone concentration of 250 μg L-1 the occurrence of an intersex individual was verified, simultaneously presenting characteristics of male and female. The results of this study evidenced the 17α-ethinyl estradiol affect the reproduction of Daphnia magna, and can affect the reproduction of other aquatic invertebrates that at long term can cause damages to aquatic populations and communities by diminishing populations and eventually leading them to the extinction.

Muitas substâncias descartadas no meio ambiente não são totalmente degradadas, podendo assim persistir no ambiente. Diversos compostos são continuamente introduzidos no ambiente podendo afetar a biota e inclusive o homem. Os fármacos são alguns desses compostos que depois de descartados podem chegar nos corpos de águas naturais, e dentre eles merecem especial atenção os hormônios sintéticos utilizados em larga escala por mulheres em todo o mundo, na forma de contraceptivos orais. O hormônio sintético 17α-etinilestradiol é um micropoluente no ambiente aquático, que pode causar distúrbios na reprodução de diversos organismos atuando como um desregulador endócrino. O presente estudo teve como objetivo principal analisar o efeito do hormônio sintético 17α-etinilestradiol sobre o cladócero Daphnia magna, por meio de testes ecotoxicológicos. Testes de toxicidade crônica foram realizados em duas gerações consecutivas deste microcrustáceo (F0 e F1). Para os testes utilizaram-se neonatas com menos de 24 horas de idade, 6 concentrações do hormônio e dois controles. Foram estabelecidas 10 réplicas com 1 indivíduo por réplica. O ensaio foi realizado em incubadora com temperatura de 25 ± 1°C e fotoperíodo de 12h claro:12h escuro, com duração de 11 (F0) e 13 dias (F1), com término coincidindo com o nascimento das neonatas da terceira ninhada no controle. Os resultados evidenciaram que a exposição ao hormônio diminuiu a fecundidade de Daphnia magna nas quatro maiores concentrações de etinilestradiol na F0 e na concentração de 1000 μg L-1 da F1, revelando maior resistência ao contaminante na segunda geração. Na maior concentração do composto, o tempo para a produção das duas primeiras ninhadas foi maior na geração F1, quando comparada ao controle. Na concentração de 250 μg L-1 verificou-se a ocorrência de um indivíduo intersexo, apresentando tanto características de macho como de fêmea. Os resultados deste estudo evidenciaram que o 17α-etinilestradiol afeta a reprodução de Daphnia magna, e que também pode afetar a reprodução de diferentes invertebrados aquáticos, o que, a longo prazo pode causar danos às populações e comunidades aquáticas, diminuindo as populações e podendo até extingui-las eventualmente. / Many substances are discarded in the environment and not completely degraded, thus persisting in the environment. Some of these are continuously introduced in the environment, affecting the biota, including man. Pharmaceutical drugs are some of these compounds that after discarded can occur in natural water bodies and among them the synthetic hormones deserve special attention for being used in large scale by women world widely, as oral contraceptives. The synthetic hormone 17α-ethinyl estradiol is therefore a micropoluent in the aquatic environment, i. e. found in low concentrations that can cause deleterious effects in the reproduction of many organisms, acting as an endocrine disruptor. The present study had as main objective to analyze the effect of the synthetic estrogen 17α-ethinyl estradiol on the cladoceran Daphnia magna, by carrying out ecotoxicological tests. Chronic toxicity tests were performed on two consecutive generations of this microcrustacean (F0 and F1). In order to perform the tests, neonates aged less than 24 hours, 6 hormones concentrations and two types of controls were used. Ten replicates were established with one individual each. The test was performed in a growth chamber at the constant temperature of 25 ± 1°C and 12 h light:12 h dark photoperiod, had the duration of 11 and 13 days for the F1 and F0 generations, respectively, coinciding with the birth of the third brood in the control. The results evidenced that the exposition to the hormone decreased D. magna fecundity in the four highest of ethinyl estradiol in F0, and in the concentration 1000 μg L-1 for the F1, indicating resistance increase in the second generation. In the highest concentration of this compound the time for the production of the first two broods were higher in the F1 generation as compared with the controls. In the hormone concentration of 250 μg L-1 the occurrence of an intersex individual was verified, simultaneously presenting characteristics of male and female. The results of this study evidenced the 17α-ethinyl estradiol affect the reproduction of Daphnia magna, and can affect the reproduction of other aquatic invertebrates that at long term can cause damages to aquatic populations and communities by diminishing populations and eventually leading them to the extinction.