Banca de DEFESA: LUA TAINA COSTA REIS

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : LUA TAINA COSTA REIS
DATA : 26/04/2019
HORA: 08:00
LOCAL: Núcleo Universitário de Telessaúde - NUTS/HUPES
TÍTULO:

INTERGENERATIONAL AND LONG-TERM EFFECTS OF GLYPHOSATE-BASED HERBICIDE IN CENTRAL NERVOUS SYSTEM

PALAVRAS-CHAVES:

Intergenerational effect; Long-term effect; Glyphosate; Endocrine disrupters.

PÁGINAS: 117
GRANDE ÁREA: Ciências Biológicas
ÁREA: Biologia Geral
RESUMO:

Glyphosate is one of the best-selling herbicides in the world under different commercial

formulations known as glyphosate-based herbicides (GBH). Agrochemicals have become

a public health problem due to increasing exposure, differences in toxicology according

to varied formulations and ability to act as endocrine disrupters altering hormone

signaling. Within the organs and biological axes affected by endocrine disrupters, the

hypothalamic-pituitary-thyroid axis (HPT) due the control and release of thyroid

hormones (HT) responsible for various biological effects and neurons/glial cells due

being susceptible to changes during the early stages of neurodevelopment, are relevant to

research the effects of herbicide exposure. In the first chapter the objective of the study

was to evaluate the endocrine disruption action of herbicides based on glyphosate (GBH)

on thyroid hormone homeostasis in the cerebellum. Pregnant Wistar rats exposed to

Roundup Transorb solution (Monsanto) were divided into 2 treatment groups (5 mg / kg

/ day and 50 mg / kg / day) and control, exposed from the 18th day of gestation (GD18)

to postnatal day 5 (PND5). Male offspring were sacrificed in PND 90 and qPCR analysis

of genes related to the metabolism and function of thyroid hormones evaluated in

cerebellar tissue. As a result, in the cerebellum tissue of exposed male pups there was

deregulation of all genes directly related to the intracellular metabolism of thyroid

hormone, TRα1, TRβ1 e TRβ2, Mct8, Oatp1c1, Dio2, Dio3. In addition, it has been shown

that treated animals presented intergenerational changes in the key regulator of epigenetic

marks Dnmt3A, indicating a possible epigenetic mechanism behind the disruptor action.

In addition, primary cerebellar cultures obtained from 8-day Wistar rats exposed to doses

ranging from 1 to 100 parts per million (ppm) over a 24-hour period induced

mitochondrial activation and decrease of GFAP positive astrocytes, although no toxicity

was observed at this dose.

The second chapter aimed to evaluate the long-term effects of suboxic doses of pure

glyphosate and GBH Roundup Transorb on neurodevelopment. Using directly exposed

neuroepithelial cells (parental cells) at the sub-toxic dose of 2.5 ppm of both glyphosate

and glyphosate-based herbicide formulations (GBH), and observing the effects on cells

that were not directly exposed (F1) to glyphosate or (GBH), we found that GBH induced

more toxic and developmental dysregulation compared to pure glyphosate. GBH

exposure activated autophagic processes, in addition to inducing dysregulation of key

neurodevelopment genes such as HES1, HES5, DDK1 and TRKB together with the

neuronal markers NESTIN, DCX, PAX6, GFAP, TUJ1 and MAP2. GBH treated F1 cells

also showed long-term changes in morphology with increased number of cells per clusters

and changes in the proportion of neuronal cells.

In summary, GBH was able to induce long-term changes in regulators of thyroid hormone

homeostasis and neurodevelopment, even at doses that did not show toxicity.

MEMBROS DA BANCA:
Externo ao Programa - 2181841 - JOSE ANTONIO MENEZES FILHO
Externo à Instituição - MARIMÉLIA APARECIDA PORCIONATTO - UNIFESP
Externo à Instituição - RAPHAEL FERREIRA QUEIROZ - UESB
Presidente - 1674313 - SUZANA TELLES DA CUNHA LIMA
Externo à Instituição - TÂNIA ARAÚJO VIEL - USP