Impacto da exposição intrauterina aos PCBs sobre o desenvolvimento embrionário da tireoide e programação do eixo hipotálamo-hipófise-tireoide dos animais da prole
Data
2024-05-28
Autores
Tavares, Evelyn Franciny Cardoso 
Orientadores
Nascimento, Caroline Serrano
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
A exposição a bifenilos policlorados (PCBs) perturba a função do eixo hipotálamohipófise-tireoide (HHT) em humanos e roedores expostos. No entanto, as consequências da exposição aos PCBs na programação do eixo HHT durante janelas críticas de desenvolvimento nunca foram relatadas. Objetivo: Investigar o impacto da exposição intrauterina aos PCBs na programação e função do eixo HHT em animais da geração F1 durante a fase adulta. Métodos: Ratas Wistar grávidas foram tratadas oralmente com óleo de milho (controle) ou óleo de milho suplementado com 50 ou 500µg de Aroclor 1254/kg/dia durante o período gestacional. A prole foi eutanasiada em dois períodos, GD20 e PND90. Hipotálamo, hipófise, tireoide, fígado, córtex e soro foram coletados. A expressão gênica e proteica foi avaliada por RT-qPCR e Western Blotting. Análises histológicas da tireoide foram realizadas, e os níveis de T3/T4 foram medidos por imunoquimioluminescência. Resultados: A exposição intrauterina aos PCBs reduziu significativamente o conteúdo de mRNA/proteína de TRH e TSHB no hipotálamo e na hipófise, respectivamente, de ratos machos e fêmeas da geração F1. Além disso, o tratamento aumentou a expressão gênica/proteica de NIS, TPO, TG e MCT8 na tireoide dos animais da prole da geração F1. Em concordância, os níveis de T4 e T3 apresentaram-se aumentados nos animais expostos aos PCBs. Tanto em machos como em fêmeas, os folículos tireoidianos estavam aumentados e preenchidos com maiores quantidades de TG do que os folículos dos ratos do grupo controle. A infiltração de células inflamatórias também foi observada, especialmente na tireoide das fêmeas. Interessantemente, houve alteração em enzimas envolvidas em processos epigenéticos de regulação da expressão gênica. A expressão de Sult1e1, enzima envolvida na degradação periférica dos hormônios tireoidianos, apresentou-se diminuída no fígado dos ratos e ratas expostos aos PCBs, enquanto a expressão de transtirretina, principal proteína de transporte de hormônios tireoidianos no plasma dos ratos, apresentou-se reduzida nas fêmeas adultas da geração F1 expostas aos PCBs. Adicionalmente, observou-se alteração na expressão de enzimas envolvidas no controle oxidativo no córtex dos animais expostos aos PCBs. Conclusões: O estudo sugere que a exposição intrauterina aos PCBs leva à hiperativação do eixo HHT em animais da geração F1 durante a fase adulta.
Exposure to polychlorinated biphenyls (PCBs) disrupts the function of the hypothalamicpituitarythyroid (HPT) axis in humans and rodents. However, the consequences of PCB exposure on HPT axis programming during critical developmental windows have never been reported. Objective: To investigate the impact of intrauterine PCB exposure on the programming and function of the HPT axis in F1 generation animals during adulthood. Methods: Pregnant Wistar rats were orally treated with either corn oil (control) or corn oil supplemented with 50 or 500 μg of Aroclor 1254/kg/day during the gestational period. The offspring rats were euthanized at two time points, GD20 and PND90. Hypothalamus, pituitary, thyroid, liver, cortex, and serum were collected. Gene and protein expression were evaluated through RTqPCR and Western Blotting. Thyroid histological analyses were performed, and T3/T4 levels were measured by immunochemiluminescence. Results: Intrauterine PCB exposure significantly reduced the mRNA/protein content of TRH and TSHB in the hypothalamus and pituitary, respectively, of both male and female F1 generation rats. Additionally, the treatment increased the gene/protein expression of NIS, TPO,TG, and MCT8 in the thyroid of F1 generation offspring. In agreement, T4 and T3 levels were elevated in the PCBexposed animals. Both male and female thyroid follicles were enlarged and filled with greater amounts of TG compared to control group rats. Inflammatory cell infiltration was also observed, particularly in the thyroid of females. Interestingly, there was an alteration in enzymes involved in the epigenetic regulation of gene expression. The expression of Sult1e1, an enzyme involved in the peripheral degradation of thyroid hormones, was decreased in the liver of PCBexposed rats, while transthyretin expression, the main thyroid hormone transport protein in rat plasma, was reduced in adult F1 generation females exposed to PCBs. Additionally, changes in the expression of enzymes involved in oxidative control were observed in the cortex of PCBexposed animals. Conclusions: The study suggests that intrauterine PCB exposure leads to hyperactivation of the HPT axis in F1 generation animals during adulthood.
Exposure to polychlorinated biphenyls (PCBs) disrupts the function of the hypothalamicpituitarythyroid (HPT) axis in humans and rodents. However, the consequences of PCB exposure on HPT axis programming during critical developmental windows have never been reported. Objective: To investigate the impact of intrauterine PCB exposure on the programming and function of the HPT axis in F1 generation animals during adulthood. Methods: Pregnant Wistar rats were orally treated with either corn oil (control) or corn oil supplemented with 50 or 500 μg of Aroclor 1254/kg/day during the gestational period. The offspring rats were euthanized at two time points, GD20 and PND90. Hypothalamus, pituitary, thyroid, liver, cortex, and serum were collected. Gene and protein expression were evaluated through RTqPCR and Western Blotting. Thyroid histological analyses were performed, and T3/T4 levels were measured by immunochemiluminescence. Results: Intrauterine PCB exposure significantly reduced the mRNA/protein content of TRH and TSHB in the hypothalamus and pituitary, respectively, of both male and female F1 generation rats. Additionally, the treatment increased the gene/protein expression of NIS, TPO,TG, and MCT8 in the thyroid of F1 generation offspring. In agreement, T4 and T3 levels were elevated in the PCBexposed animals. Both male and female thyroid follicles were enlarged and filled with greater amounts of TG compared to control group rats. Inflammatory cell infiltration was also observed, particularly in the thyroid of females. Interestingly, there was an alteration in enzymes involved in the epigenetic regulation of gene expression. The expression of Sult1e1, an enzyme involved in the peripheral degradation of thyroid hormones, was decreased in the liver of PCBexposed rats, while transthyretin expression, the main thyroid hormone transport protein in rat plasma, was reduced in adult F1 generation females exposed to PCBs. Additionally, changes in the expression of enzymes involved in oxidative control were observed in the cortex of PCBexposed animals. Conclusions: The study suggests that intrauterine PCB exposure leads to hyperactivation of the HPT axis in F1 generation animals during adulthood.
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Citação
TAVARES, Evelyn Franciny Cardoso. Impacto da exposição intrauterina aos PCBs sobre o desenvolvimento embrionário da tireoide e programação do eixo hipotálamo-hipófise-tireoide dos animais da prole. 2024. 56 f. Dissertação em Mestrado em Endocrinologia e Metabologi) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP). São Paulo, 2024.a)