Pesticide toxicogenomics across scales: in vitro transcriptome predicts mechanisms and outcomes of exposure in vivo

Porreca, Immacolata; D’Angelo, Fulvio; Franceschi, Lucia De; Ceccarelli, Michele; Iolascon, Achille; Zamò, Alberto; Russo, Filomena; Ravo, Maria; Tarallo, Roberta; Scarfò, Marzia; Weisz, Alessandro; Felice, Mario De; Mallardo, Massimo; Ambrosino, Concetta

doi:10.1038/srep38131

Cited by 22 publications

(25 citation statements)

References 40 publications

(62 reference statements)

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“…Despite this limitation, in vitro toxicogenomics managed to predict modes of action with longer exposure times. Notably, interference with thyrotrope growth was the main mechanism identified (126).…”

Section: In Vitro Evidence Of Thyroid Disruptionmentioning

confidence: 99%

Pesticides With Potential Thyroid Hormone-Disrupting Effects: A Review of Recent Data

et al. 2019

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Plant Protection Products, more commonly referred to as pesticides and biocides, are used to control a wide range of yield-reducing pests including insects, fungi, nematodes, and weeds. Concern has been raised that some pesticides may act as endocrine disrupting chemicals (EDCs) with the potential to interfere with the hormone systems of non-target invertebrates and vertebrates, including humans. EDCs act at low doses and particularly vulnerable periods of exposure include pre-and perinatal development. Of critical concern is the number of pesticides with the potential to interfere with the developing nervous system and brain, notably with thyroid hormone signaling. Across vertebrates, thyroid hormone orchestrates metamorphosis, brain development, and metabolism. Pesticide action on thyroid homeostasis can involve interference with TH production and its control, displacement from distributor proteins and liver metabolism. Here we focused on thyroid endpoints for each of the different classes of pesticides reviewing epidemiological and experimental studies carried out both in in vivo and in vitro. We conclude first, that many pesticides were placed on the market with insufficient testing, other than acute or chronic toxicity, and second, that thyroid-specific endpoints for neurodevelopmental effects and mixture assessment are largely absent from regulatory directives.

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Section: In Vitro Evidence Of Thyroid Disruptionmentioning

confidence: 99%

Pesticides With Potential Thyroid Hormone-Disrupting Effects: A Review of Recent Data

et al. 2019

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“…Contrastingly, recent studies have shown that, after repeated CPF treatment, the mice seemed to develop some tolerance to CPF-induced effects, suggesting that the detoxifying mechanisms are possibly involved in the induction of tolerance. Compensatory mechanisms were not active in thyroids of mice treated with the same CPF concentrations [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…The present study aimed to evaluate the effects of a chronical exposure to the environmental detected concentrations of CPF in mice exposed in utero and postnatally to the pesticide. The pregnant females were fed for all the pregnancy and the nursing period [ 24 ] with three different concentrations of CPF (0.1 mg/kg/day, 1 mg/kg/day, 10 mg/kg/day), that are commonly found in fruits and vegetables. Afterwards, weaned mice were fed in the same manner until the time of sacrifice.…”

Section: Introductionmentioning

confidence: 99%

Specific Effects of Chronic Dietary Exposure to Chlorpyrifos on Brain Gene Expression—A Mouse Study

Pallotta

Ronca

Carotenuto

et al. 2017

IJMS

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Chlorpyrifos (CPF) is an organophosphate insecticide used to control pests on a variety of food and feed crops. In mammals, maternal exposure to CPF has been reported to induce cerebral cortex thinning, alteration of long-term brain cognitive function, and Parkinson-like symptoms, but the mechanisms of these processes are not fully understood. In this study, we aimed to gain a deeper understanding of the alterations induced in the brains of mice chronically exposed to CPF by dietary intake. For our purpose, we analysed F1 offspring (sacrificed at 3 and 8 months) of Mus musculus, treated in utero and postnatally with 3 different doses of CPF (0.1-1-10 mg/kg/day). Using RT2 Profiler PCR Arrays, we evaluated the alterations in the expression of 84 genes associated with neurodegenerative diseases. In the brains of exposed mice, we evidenced a clear dose–response relationship for AChE inhibition and alterations of gene expression. Some of the genes that were steadily down-regulated, such as Pink1, Park 2, Sv2b, Gabbr2, Sept5 and Atxn2, were directly related to Parkinson’s onset. Our experimental results shed light on the possibility that long-term CPF exposure may exert membrane signalling alterations which make brain cells more susceptible to develop neurodegenerative diseases.

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“…RNAseq experiments were previously conducted on PCCL3 cell line and have been already described, also reporting details on cluster building approach [32].…”

Section: Methodsmentioning

confidence: 99%

A Toxicogenomic Approach Reveals a Novel Gene Regulatory Network Active in In Vitro and In Vivo Models of Thyroid Carcinogenesis

Reale

Russo

Credendino

et al. 2019

IJERPH

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Epidemiological and experimental studies emphasize the link between environmental chemicals exposure and thyroid cancer. However, this association is strongly debated and the mechanisms of action of environmental thyroid carcinogens still need to be identified. The analysis of in vitro transcriptomic data developed to investigate the effects of chlorpyrifos on immortalized thyrocytes highlighted the impaired expression of genes involved in endodermal carcinogenesis. This endodermal carcinogenic gene-network (ECGN, including Zfp36l2, Dmbt1, Ddit4), was validated in cellular and mouse models of thyroid carcinogenesis, characterized by the constitutive activation of the mitogen-activated protein kinase (MAPK) pathway and in immortalized thyrocytes exposed to tetrachlorodibenzo-p-dioxin (TCDD) and chlorpyrifos (CPF). The mRNA levels of Zfp36l2, Dmbt1 and Ddit4 were increased in models characterized by MAPK activation or following TCDD exposure, whereas they were inhibited by CPF exposure. Overall, the ECGN transcripts identify a novel gene-regulatory network associated with thyroid carcinogenesis promoted by genetic mutation or by environmental carcinogens. The latter have opposite effects on the modulation of the ECGN transcripts according to their mechanisms of action in promoting carcinogenesis. Therefore, the analyses of ECGN might be helpful in discriminating compounds that promote cellular survival associated or not to proliferation of thyrocytes.

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Pesticide toxicogenomics across scales: in vitro transcriptome predicts mechanisms and outcomes of exposure in vivo

Cited by 22 publications

References 40 publications

Pesticides With Potential Thyroid Hormone-Disrupting Effects: A Review of Recent Data

Pesticides With Potential Thyroid Hormone-Disrupting Effects: A Review of Recent Data

Specific Effects of Chronic Dietary Exposure to Chlorpyrifos on Brain Gene Expression—A Mouse Study

A Toxicogenomic Approach Reveals a Novel Gene Regulatory Network Active in In Vitro and In Vivo Models of Thyroid Carcinogenesis

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