Intergenerational thyroid hormone homeostasis imbalance in cerebellum of rats perinatally exposed to glyphosate-based herbicide

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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 ; Giannocco, Gisele ; Lima Costa, Silvia ; Dias da Silva, Magnus Regios ; Telles da Cunha Lima, Suzana

• Tipo de documento: Artigo Científico
• Fonte: ENVIRONMENTAL TOXICOLOGY; v. 36, n. 6, p. 12-pg., 2021-01-29.

Resumo

Agrochemicals became a public health concern due to increased human exposure and possible endocrine disruption effects in several organs, including the brain. Thyroid hormones controls neurodevelopment, which turn them sensitive to endocrine disruptors (EDs). In this work, we evaluated the effect of glyphosate-based herbicides (GBH) as an intergenerational endocrine disrupter on thyroid homeostasis in cerebellar cells. Female pregnant Wistar rats were exposed to Roundup Transorb (R) solution at 5 and 50 mg/kg/day, from gestation day 18 to post-natal day 5 (P5). Cerebellum of male offspring was used to evaluate gene expression. The mRNA levels of thyroid hormone receptors, hormonal conversion enzymes, hormone transporters, as well as, de novo epigenetic regulators were altered, with some of these genes presenting a non-monotonic dose response. Furthermore, metabolomic profile correlation with tested dose demonstrated altered metabolic profile, in agreement with cerebellar gene alterations. Moreover, cerebellar primary cultures exposed to non-toxic GBH concentration presented a decrease level in glial fibrillary acidic protein, a protein regulated by endocrine signals. In conclusion, our results indicate that animals exposed to non-toxic GBH doses during perinatal phase carry intergenerational alterations in key regulators of cellular thyroid hormone homeostasis and epigenetic controllers in adulthood, indicating the possible ED effect of GBH based on epigenetic alterations. (AU)

• Processo FAPESP: 18/22763-0 - DNA antigo, bioengenharia e "organoides" de cérebro: estudo da homeostase do hormônio tiroidiano e marcadores da Doença de Alzheimer em células tronco com gene NOVA1 editado por CRISPR
• Beneficiário: Janaína Sena de Souza
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 13/26851-7 - Estudo in vivo do efeito dos desreguladores endócrinos glifosato e bisfenol-A sobre o eixo hipotálamo-hipófise-tiroide
• Beneficiário: Maria Izabel Chiamolera
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/07053-3 - Efeito do hormônio tiroidiano no encéfalo de camundongos 3xTg-AD, modelo da Doença de Alzheimer, no metabolismo da glicose e colesterol
• Beneficiário: Janaína Sena de Souza
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado