Genetic background and window of exposure contribute to thyroid dysfunction promoted by low-dose exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice
| Autor: | Immacolata Porreca, Luca Roberto, Concetta Ambrosino, Mario De Felice, Maria Marotta, Emanuele Carchia, Nicola Antonino Russo, Massimo Mallardo, Filomena Russo, Carla Reale |
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| Přispěvatelé: | Reale, C., Porreca, I., Russo, F., Marotta, M., Roberto, L., Russo, N. A., Carchia, E., Mallardo, Massimo., De Felice, M., Ambrosino, C. |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Polychlorinated Dibenzodioxins Time Factors Thyroid Nuclear Factor 1 Thyroid Gland lcsh:Medicine Haploinsufficiency Mice NF-KappaB Inhibitor alpha Gene expression Medicine lcsh:Science Sex Characteristics Multidisciplinary Thyroid Phenotype Dose–response relationship medicine.anatomical_structure Polychlorinated Dibenzodioxin Female Thyroid function Signal Transduction medicine.medical_specialty endocrine system Time Factor Article Cell Line 03 medical and health sciences PAX8 Transcription Factor Hypothyroidism In vivo Internal medicine Animals Dose-Response Relationship Drug business.industry Animal lcsh:R Transcription Factor RelA Sex Characteristic 8-tetrachlorodibenzo-p-dioxin genetic Pax8 Nkx2-1 hypothyroidism humans Furthermore 030104 developmental biology Endocrinology lcsh:Q Tumor Suppressor Protein p53 business PAX8 |
| Zdroj: | Scientific Reports Scientific reports (Nature Publishing Group) 8 (2018). doi:10.1038/s41598-018-34427-2 info:cnr-pdr/source/autori:Reale C.; Porreca I.; Russo F.; Marotta M.; Roberto L.; Russo N.A.; Carchia E.; Mallardo M.; De Felice M.; Ambrosino C./titolo:Genetic background and window of exposure contribute to thyroid dysfunction promoted by low-dose exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice/doi:10.1038%2Fs41598-018-34427-2/rivista:Scientific reports (Nature Publishing Group)/anno:2018/pagina_da:/pagina_a:/intervallo_pagine:/volume:8 Scientific Reports, Vol 8, Iss 1, Pp 1-11 (2018) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-34427-2 |
| Popis: | Genetic and environmental factors contribute to thyroid diseases. Although still debated, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is thought to induce thyroid dysfunction in humans and rodents. The data here reported point out the contribution of the exposure window and genetic background in mediating the low-dose TCDD effects on thyroid. Indeed, early (from E0.5 to PND30) and low-dose (0,001 μg/kg/day) TCDD exposure reduced the circulating fT4 and altered the expression of thyroid specific transcripts. The role of genetic components was estimated monitoring the same markers in Pax8+/− and Nkx2-1+/− mice, susceptible to thyroid dysfunction, exposed to 0, 1 μg/kg/day TCDD from E15.5 to PND60. Haploinsufficiency of either Pax8 or Nkx2-1 genes exacerbated the effects of the exposure impairing the thyroid enriched mRNAs in sex dependent manner. Such effect was mediated by mechanisms involving the Nkx2-1/p53/p65/IĸBα pathway in vitro and in vivo. Foetal exposure to TCDD impaired both thyroid function and genes expression while thyroid development and differentiation did not appear significantly affected. In mouse, stronger effects were related to earlier exposure or specific genetic background such as either Pax8 or Nkx2-1 haploinsufficiency, both associated to hypothyroidism in humans. Furthermore, our data underline that long exposure time are needed to model in vitro and in vivo results. |
| Databáze: | OpenAIRE |
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