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Next Generation Sequencing to assess pesticides capacity in vitro to act as agonists/antagonists of the thyroid hormone nuclear receptors

ABSTRACT: Next Generation Sequencing to assess pesticides capacity in vitro to act as agonists/antagonists of the thyroid hormone nuclear receptors

PROVIDER: PRJNA718198 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14092411.fastq.gz	Fastqsanger.gz
	SRR14092412.fastq.gz	Fastqsanger.gz
	SRR14092413.fastq.gz	Fastqsanger.gz
	SRR14092414.fastq.gz	Fastqsanger.gz
	SRR14092415.fastq.gz	Fastqsanger.gz

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Next Generation Sequencing to assess pesticides capacity in vitro to act as agonists/antagonists of the thyroid hormone nuclear receptors

Project description:We combined in vitro tests to fully assess the capacity of pesticides to act as thyroid hormone disruptors (THD). Pesticides which were active in these tests were selected for a transcriptome analysis of neural cells. We took advantage of this technique to decipher what were the transcriptomic effects of these chemical in vitro. We also compared the expression of thyroid hormone responsive genes in presence or absence of the pesticides to determine if the transcriptomic changes could impact thyroid hormone receptor signaling. Although some pesticides elicit a cellular response, which sometimes interferes with thyroid hormone signaling, we found no evidence that they can act as TRα1 agonists or antagonists. We conclude that their neurodevelopmental toxicity in mammals is not explained by an alteration of the neural cell response to thyroid hormone.

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<i>In vitro</i> assessment of pesticides capacity to act as agonists/antagonists of the thyroid hormone nuclear receptors.

Project description:Chemicals acting as thyroid hormone disruptors (THDs) are of a particular concern for public health, considering the importance of this hormone in neurodevelopment and metabolic processes. They might either alter the circulating level of thyroid hormone (TH) or interfere with the cellular response to the hormonal stimulation. In order to assess this later possibility we selected 39 pesticides and combined several in vitro tests. Reporter assays respectively addressed the transactivation capacity of the full-length TH nuclear receptor TRα1, the transactivation capacity of its C-terminal ligand binding domain, or the ability of the hormone to destabilize the interaction between TRα1 and the transcriptional corepressor NcoR. Although some pesticides elicit a cellular response, which sometimes interferes with TH signaling, RNA-seq analysis provided no evidence that they can act as TRα1 agonists or antagonists. Their neurodevelopmental toxicity in mammals cannot be explained by an alteration of the response to TH.

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