In vivo study of the effects of the endocrine disruptors glyphosate and bisphenol-A on the hypothalamic-pituitary-thyroid axis

• Grant number: 13/26851-7
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2014
• End date: November 30, 2016
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Maria Izabel Chiamolera
• Grantee: Maria Izabel Chiamolera
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Endocrine Disruptors (ED) can be defined as exogenous compounds with the potential to alter standard hormone regulation and endocrine system. Such interference may occur in the production, release, metabolism and elimination of hormones. Furthermore, these substances can mimic natural hormone actions, causing changes in normal physiological functions. Similarly to hormones, EDs operate on very low dose and tissue specific manner. The endocrine effects may also show non-traditionally dose-response curves, in which low doses may have more important toxic effects. The age at which the individual is exposed to these substances is also important, early embryonic development exposition is markedly different from those with exposures during adulthood. In this regard, fetal exposure to EDs can be considered as the basis for understanding adult diseases. In this project we opted to study the two major currently used EDs that might affect men's health: Bisphenol A (BPA) and glyphosate. It has been demonstrated that thyroid receptors (TR) binding of BPA appears to have a lower affinity than that of the estrogen receptors (ER), whereas other authors believe that BPA interact with TR as an indirect antagonist of thyroid hormones and their effects on the action of thyroid hormones in vivo are dependent on the composition and relative abundance of available cell cofactors. However, the real effect of this substance in the regulation of the HPT axis in vivo remains to be clarified. Another substance to be analyzed in this project is glyphosate, which is an herbicide widely used, especially in transgenic plantations. Preliminary data displayed by our collaborative group of Dr. Romano have shown that prenatal exposure of rats with a compound containing glyphosate (50mg/kg) resulted in a decrease of the mRNA content of TSH beta subunit, but other than that little is known about how glyphosate can influence the regulation of the HPT axis. Therefore, we aim at studying the influence of perinatal exposure to BPA and glyphosate in rats HHT axis. To reach that goal we will evaluate hormonal concentration and related gene expression profile in order to estimate HHT axis function. Based on gene expression findings it will be performed studies to evaluate protein expression using Western Blotting. Methylation status of a panel of selected genes will be assessed using another panel for microRNA analyzes in order to identify possible changes in epigenetic marks generated by the two ED compounds. Moreover, we will evaluate the metabolic phenotypic profile in animals exposed to these compounds by measuring a series of metabolites using metabolomics analysis. Therefore, the results of this project could guide to a better understand in the mechanisms of action of these two EDs and help assess the possible impact of these on public health, and contribute to programs for prevention and control of current exposure to these products. (AU)

Scientific publications

(8)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

OLIVEIRA, KAREN JESUS; CHIAMOLERA, MARIA ISABEL; GIANNOCCO, GISELE; PAZOS-MOURA, CARMEN CABANELAS; ORTIGA-CARVALHO, TANIA MARIA. Thyroid function disruptors: from nature to chemicals. JOURNAL OF MOLECULAR ENDOCRINOLOGY, v. 62, n. 1, p. R1-R19, JAN 2019. (13/26851-7)

DA CONCEICAO, RODRIGO RODRIGUES; DE SOUZA, JANAINA SENA; DE OLIVEIRA, KELEN CARNEIRO; ROMANO, RENATA MARINO; DE BARROS MACIEL, RUI MONTEIRO; DIAS-DA-SILVA, MAGNUS REGIOS; ROMANO, MARCO AURELIO; CHIAMOLERA, MARIA IZABEL; GIANNOCCO, GISELE. Evaluation of neuroglobin and cytoglobin expression in adult rats exposed to silver nanoparticles during prepubescence. METABOLIC BRAIN DISEASE, v. 34, n. 3, p. 705-713, JUN 2019. (13/26851-7)

DE SOUZA, JANAINA SENA; LAUREANO-MELO, ROBERTO; HERAI, ROBERTO HIROCHI; DA CONCEICAO, RODRIGO RODRIGUES; OLIVEIRA, KELEN CARNEIRO; COTRIM GUERREIRO DA SILVA, ISMAEL DALE; DIAS-DA-SILVA, MAGNUS REGIOS; ROMANO, RENATA MARINO; ROMANO, MARCO AURELIO; DE BARROS MACIEL, RUI MONTEIRO; et al. Maternal glyphosate-based herbicide exposure alters antioxidant-related genes in the brain and serum metabolites of male rat offspring. NeuroToxicology, v. 74, p. 121-131, SEP 2019. (13/26851-7, 17/07053-3)

COSTA REIS, LUA TAINA; SENA DE SOUZA, JANAINA; HIROCHI HERAI, ROBERTO; CUNHA, EDUARDO BRUNETTI; RIBEIRO PEREIRA SOARES, JANAINA; SANTOS EL-BACHA, RAMON; DIOGENES AMARAL DA SILVA, VICTOR; AURELIO ROMANO, MARCO; MARINO ROMANO, RENATA; IZABEL CHIAMOLERA, MARIA; et al. Intergenerational thyroid hormone homeostasis imbalance in cerebellum of rats perinatally exposed to glyphosate-based herbicide. ENVIRONMENTAL TOXICOLOGY, v. 36, n. 6, p. 12-pg., 2021-01-29. (18/22763-0, 13/26851-7, 17/07053-3)

COSTA REIS, LUA TAINA; SENA DE SOUZA, JANAINA; HIROCHI HERAI, ROBERTO; CUNHA, EDUARDO BRUNETTI; RIBEIRO PEREIRA SOARES, JANAINA; SANTOS EL-BACHA, RAMON; DIOGENES AMARAL DA SILVA, VICTOR; AURELIO ROMANO, MARCO; MARINO ROMANO, RENATA; IZABEL CHIAMOLERA, MARIA; et al. ntergenerational thyroid hormone homeostasis imbalance in cerebellum of rats perinatally exposed to glyphosate-based herbicid. ENVIRONMENTAL TOXICOLOGY, v. 36, n. 6, JAN 2021. (17/07053-3, 18/22763-0, 13/26851-7)

DA CONCEICAO, RODRIGO RODRIGUES; DE SOUZA, JANAINA SENA; DE OLIVEIRA, KELEN CARNEIRO; DE BARROS MACIEL, RUI MONTEIRO; ROMANO, MARCO AURELIO; ROMANO, RENATA MARINO; DIAS DA SILVA, MAGNUS REGIOS; CHIAMOLERA, MARIA IZABEL; GIANNOCCO, GISELE. Anatomical specificity of the brain in the modulation of Neuroglobin and Cytoglobin genes after chronic bisphenol a exposure. METABOLIC BRAIN DISEASE, v. 32, n. 6, p. 1843-1851, DEC 2017. (13/26851-7)

ALVES, THALITA G.; MELO, MARIA CLARA DE C.; KASAMATSU, TERESA S.; OLIVEIRA, KELEN C.; DE SOUZA, JANAINA SENA; DA CONCEICAO, RODRIGO RODRIGUES; GIANNOCCO, GISELE; DIAS-DA-SILVA, MAGNUS R.; CHIAMOLERA, MARIA IZABEL; VIEIRA, JOSE GILBERTO. Novel immunoassay for TSH measurement in rats. ARCHIVES OF ENDOCRINOLOGY METABOLISM, v. 61, n. 5, p. 460-463, SEP-OCT 2017. (13/26851-7)

DE SOUZA, JANAINA SENA; LETRO KIZYS, MARINA MALTA; DA CONCEICAO, RODRIGO RODRIGUES; GLEBOCKI, GABRIEL; ROMANO, RENATA MARINO; ORTIGA-CARVALHO, TANIA MARIA; GIANNOCCO, GISELE; COTRIM GUERREIRO DA SILVA, ISMAEL DALE; DIAS DA SILVA, MAGNUS REGIOS; ROMANO, MARCO AURELIO; et al. Perinatal exposure to glyphosate-based herbicide alters the thyrotrophic axis and causes thyroid hormone homeostasis imbalance in male rats. Toxicology, v. 377, p. 25-37, FEB 15 2017. (14/06834-3, 14/15948-2, 13/26851-7, 12/01628-0)