The Window of Exposition Interferes with Bisphenol a Disruptive Action in Thyroid Hormone and Metabolomic Profile in Male Rats

Presentation Number: SAT 247
Date of Presentation: April 1st, 2017

Felipe A Jacob1, Marina M.L. Kisys2, Rodrigo R Conceiçao1, Janaina S Souza3, Kelen C Oliveira1, Teresa Kasamatsu4, Gisele Giannocco5, Renata M. Romano6, Magnus R. Dias da Silva4, Marco A. Romano7, Ismael D. Cotrim Guerreiro da Silva8 and Maria Izabel Chiamolera*9
1Universidade Federal de Sao Paulo - UNIFESP, 2Universidade Federal de Sao Paulo - UNIFESP, Sao Paulo, Brazil, 3Univesidade Federal de Sao Paulo - UNIFESP, 4Universidade Federal de São Paulo - UNIFESP, São Paulo, Brazil, 5Universidade Federal de São Paulo - UNIFESP, La Jolla, CA, 6Universidade Estadual do Centro-Oeste, 7Universidade Estadual do Centro-Oeste, Guarapuava, Brazil, 8Universidade Federal de Sao Paulo - UNIFESP and Grupo Fleury, 9Universidade Federal de Sao Paulo - UNIFESP, Sao Paulo, BRAZIL


Bisphenol A (BPA) is part of plastic materials, and it has been associated with endocrine disruption mostly in gonadal axis. However, in the last few years, in vitro and in vivo experiments had showed an antagonist role of BPA to thyroid hormone receptors (TRs). Therefore, the present study goal is to test BPA action on thyroid axis and in the metabolomic profile in vivo at different doses and in two different windows of exposition, peripubertal (PP) and perinatal (PN).

PP male Wistar rats were treated with 0, 5 and 25 mg/kg/day (C, T5 and T25) of BPA diluted in corn oil and administered per os (gavage), from postnatal day 23 (PND23) to PND58 and they were sacrificed at PND102. In PN, pregnant females were exposed to 0, 0.5 or 5 mg/kg/day (C, T0.5 and T5) of BPA, from gestational day 18 to PND5, and the male offspring were sacrificed at PND90. Serum concentrations of TSH, T3 and T4 were performed using commercial kits, and metabolomic profile was performed using the the AbsoluteIDQ p180 kit from Biocrates.

Animals exposed to BPA during the peripuberal period presented an elevation of TSH (p<0.01) with lower levels of total T4 (p<0.01 for T5 and p<0.05 for T25), paradoxically to an increase of total T3 (p<0.01 for T5). In contrast, perinatal treated animals had a completely different thyroid hormone report, with reduction in TSH concentration (p<0.001 for T0.5 and p<0.01 for T5) and elevation in all treated groups for both T3 (p<0.001) and T4 (p<0.05). The metabolomics profile follows also presented distinct patterns between the two different treatments. PP animals presented a profile similar to the one presented by animals with hypothyroidism, in around 50% of the main metabolites alterations, both hypothyroid and BPA exposed animals presented markedly increase in the long chain glycerophospholipids. While the PN animals have higher levels of acylcarnitines, similar to hyperthyroid animals, with a similarity in the main altered metabolites of around 60%.

In conclusion, BPA-exposed animal thyroid and metabolic profiles are very distinct depending on when the exposition occurs. Animals exposed in the peripubertal period are similar to what it is expected for hypothyroid states, with a unique hormonal profile similar to the one found in MCT8 mutation, and metabolic characterization similar to the hypothyroidism, which could be explained by BPA antagonistic action in TRs showed in former studies. In contrast, the perinatal exposition reflects in adulthood generating an animal with similar characteristics to a hyperthyroid one, demonstrating that the window of exposition is very important for the repercussion of BPA exposition in the thyroid axis.


Nothing to Disclose: FAJ, MMLK, RRC, JSS, KCO, TK, GG, RMR, MRD, MAR, IDCGD, MIC