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

Author(s):Show less -

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

• Document type: Journal article
• Source: ENVIRONMENTAL TOXICOLOGY; v. 36, n. 6, p. 12-pg., 2021-01-29.

Abstract

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)

• FAPESP's process: 18/22763-0 - Ancient DNA, bioengineering and brain "organoids": study of thyroid hormone homeostasis and Alzheimer's Disease markers in NOVA1 gene CRISPR edited stem cells
• Grantee: Janaína Sena de Souza
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 13/26851-7 - In vivo study of the effects of the endocrine disruptors glyphosate and bisphenol-A on the hypothalamic-pituitary-thyroid axis
• Grantee: Maria Izabel Chiamolera
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/07053-3 - Effect of thyroid hormone on the brain of 3xTg-AD mice, model of Alzheimer's Disease, on glucose and cholesterol metabolism
• Grantee: Janaína Sena de Souza
• Support Opportunities: Scholarships in Brazil - Post-Doctoral