Neurobehavioral and Metabolic Effects of Prenatal Low-Dose Chlorpyrifos in C57BL/6J Mice
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Orbitrap Fusion Lumos
ORGANISM(S): Mus <mouse, Genus> (ncbitaxon:10088)
SUBMITTER: 
Alan K. Jarmusch
PROVIDER: MSV000097287 | MassIVE | Tue Mar 11 08:29:00 GMT 2025
REPOSITORIES: MassIVE
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Project description:Untargeted metabolomics on mouse brain samples exposed to chlorpyrifos (0, 0.5, 5 mg/kg)
2025-03-11 | MSV000097287 | GNPS
Project description:Chlorpyrifos (CPF) is an organophosphorus (OP) insecticide that is still widely used despite statutory restrictions on home use. CPF is converted to chlorpyrifos oxon (CPO) by oxidative desulfuration in liver. Paraoxonase (PON1) polymorphisms affects the catalytic efficiency of the hydrolysis of OPs, including CPO. We used both wt (PON1+/+) and PON1 knockout (PON1-/-) mice and PON1-/- mice carrying transgenes encoding the human alloforms tgHuPON1Q192 and tgHuPON1R192 to gain insight into the mechanisms of neurotoxicity of CPO throughout postnatal development, and to ascertain the importance of the PON1Q192R polymorphism for protecting against developmental toxicity of CPO. Whole-genome microarrays were used to measure gene expression changes associated with chronic CPO exposure of developing (PND 4-21) PON1-/-, tgHuPON1Q192R transgenic and PON1+/+ mice. Expression profiles are derived from cerebella from wild-type C57/Bl6 and PON1-/- on a C57/Bl6 background and two transgenic strains (tgHuPON1Q192, tgHuPON1R192) expressing either human PON1Q192 or human PON1R192 on the PON1-/- C57/Bl6 background. The mice were subjected to chronic postnatal exposure to CPO (CPO). Transgenic, PON1-KO and WT neonatal mice either treated with control (DMSO), 0.35 mg*kg-1*day-1 CPO or 0.5 mg*kg-1*day-1 CPO daily from PND 4 to PND 21. Chlorpyrifos (CPF) is converted to chlorpyrifos oxon (CPO) by oxidative desulfuration in liver. 55 arrays, 12 experimental groups (strain + treatment), due to QC issues the replicates are as follows; PON1-KO-0.35 (5), PON1-KO-.O5 (3), PON1-KO-DMSO (4), PON1-Q129-0.35 (5), PON1-Q129-0.5 (5), PON1-Q129-DMSO (4), PON1-R129-0.35 (5), PON1-R129-0.5 (5), PON1-R129-DMSO (4), WT-0.35 (6), WT-0.5 (3), WT-DMSO (6)
2011-11-09 | E-GEOD-25250 | biostudies-arrayexpress
Project description:Transcriptional profile of C. elegans comparing control vs. nematodes treated with 0.5 mg/ml of Chlorpyrifos and 1mg/ml of Diazinon (DZN) at 16°C. Toxicant was added to agar and nematode culture on petri dishes for 72h before harvesting.
2010-07-22 | GSE16698 | GEO
Project description:Chlorpyrifos oxon (CPO), the toxic metabolite of the organophosphorus (OP) insecticide chlorpyrifos, causes developmental neurotoxicity in humans and rodents. CPO is hydrolyzed by paraoxonase-1 (PON1), with protection determined by PON1 levels and the human Q192R polymorphism. To examine how the Q192R polymorphism influences fetal toxicity associated with gestational CPO exposure, we measured biomarker inhibition and fetal-brain gene expression in wild-type (PON1+/+), PON1-knockout (PON1-/-), and tgHuPON1R192 and tgHuPON1Q192 transgenic mice. Pregnant mice exposed dermally to 0, 0.50, 0.75 or 0.85 mg/kg/d CPO from gestational days (GD) 6 through 17 were sacrificed on GD18. Biomarkers of CPO exposure inhibited in maternal tissues included brain acetylcholinesterase (AChE), RBC acylpeptide hydrolase (APH), plasma butyrylcholinesterase (BChE) and carboxylesterase (CES). Fetal plasma BChE was inhibited in PON1-/- and tgHuPON1Q192, but not PON1+/+ or tgHuPON1R192 mice. Fetal brain AChE and plasma CES were inhibited in PON1-/- mice, but not in other genotypes. Pregnant mice (wild type (WT), PON1-knockout (KO), tgHuPON1R192 (R-tg) and tgHuPON1Q192 (Q-tg)) were exposed to various amounts of CPO (0, 0.5, 0.75 and 0.85 mg/kg/d) for 12 days (gestational days 6-17). On gestational day 18, dams were sacrificed and fetal brains were collected. A total of 264 fetal brains from 80 dams were processed to extract total RNA using TRIZOL and the QIAamp Tissue kit from QIAGEN. Microarray analysis was performed using the fetuses of 5 dams per experimental group (total RNA was pooled from individual fetal brains from each dam). The dams used for fetal-brain microarray analysis were selected using a random-number generator, after first eliminating dams with brain AChE activities > 1.5 SD compared to the mean for their treatment group. RNA samples isolated from individual fetal brains from each dam were combined, then labeled and hybridized to Affymetrix Mouse Gene 1.0 ST microarrays.
2014-08-04 | E-GEOD-58103 | biostudies-arrayexpress
Project description:Chlorpyrifos oxon (CPO), the toxic metabolite of the organophosphorus (OP) insecticide chlorpyrifos, causes developmental neurotoxicity in humans and rodents. CPO is hydrolyzed by paraoxonase-1 (PON1), with protection determined by PON1 levels and the human Q192R polymorphism. To examine how the Q192R polymorphism influences fetal toxicity associated with gestational CPO exposure, we measured biomarker inhibition and fetal-brain gene expression in wild-type (PON1+/+), PON1-knockout (PON1-/-), and tgHuPON1R192 and tgHuPON1Q192 transgenic mice. Pregnant mice exposed dermally to 0, 0.50, 0.75 or 0.85 mg/kg/d CPO from gestational days (GD) 6 through 17 were sacrificed on GD18. Biomarkers of CPO exposure inhibited in maternal tissues included brain acetylcholinesterase (AChE), RBC acylpeptide hydrolase (APH), plasma butyrylcholinesterase (BChE) and carboxylesterase (CES). Fetal plasma BChE was inhibited in PON1-/- and tgHuPON1Q192, but not PON1+/+ or tgHuPON1R192 mice. Fetal brain AChE and plasma CES were inhibited in PON1-/- mice, but not in other genotypes.
2014-08-04 | GSE58103 | GEO
Project description:Zebrafish embryos have been exposed to Chlorpyrifos from 24 to 48 hours post fertilization
2016-10-14 | GSE88704 | GEO
Project description:Transcriptional profile of C. elegans comparing control vs. nematodes treated with 0.5 mg/ml of Chlorpyrifos and 1mg/ml of Diazinon (DZN) at 16°C. Toxicant was added to agar and nematode culture on petri dishes for 72h before harvesting. One condition experiment with six biological replicates in a dye swap design.
2010-07-22 | E-GEOD-16698 | biostudies-arrayexpress
Project description:3,5,6-Trichloro-2-pyridinol (TCP) is a primary degradation product of chlorpyrifos and chlorpyrifos-methyl. TCP has longer half-life in soil and greater solubility in water than its parent compound, and cause wide contamination in environments. However, studies about the toxic effects of TCP are limited and outdate. In this study, 5 mg/kg/day, 50 mg/kg/day, and 150 mg/kg/day TCP were given to male mice through gavage for four weeks. As a result, the final body weights of TCP treated groups were significantly lower than control, and the relative organ weights of the liver and kidney were significantly higher than that of control. In addition, NMR-based metabolomics was used to investigate the toxic effects of TCP. It was found that a total of 39 serum metabolites were significantly changed in the TCP-treated groups, and these metabolites are related to hepatotoxicity and nephrotoxicity. These results were also confirmed by histopathology, serum biochemical, and oxidative stress analysis. In addition, metabolic disturbances due to TCP exposure were also observed based on altered metabolites. As far as we know, these results are the first to show the metabolomic toxicity of TCP, which warrants further research.
2017-05-05 | MTBLS275 | MetaboLights
Project description:Transcriptional profiling of mussel (Mytilus galloprovincialis) digestive gland tissue comparing control tissue with tissue obtained from animals exposed to sublethal amounts of Chlorpyrifos, animals injected into the posterior adductor muscle with 25 pico-moles 17β-estradiol (E2) and animals pre-exposed for three days to the pesticide and further injected with E2. Background: Many pesticides have been shown to act as endocrine disrupters. Although the potencies of currently used pesticides as hormone agonists/antagonists in vitro are low compared with those of natural ligands, their ability to act via multiple mechanisms might enhance the biological effect. The organophosphate Chlorpyrifos (CHP) has been shown to be weakly estrogenic and cause adverse neurodevelopmental effects in mammals. However, no information is available on the possible endocrine effects of CHP in aquatic organisms. In the digestive gland of the bivalve Mytilus galloprovincialis, a target tissue for the action of both estrogens and pesticides, the possible effects of CHP on the responses to the natural estrogen 17β-estradiol (E2) were investigated. Methodology/Principal findings: Mussels were exposed to CHP (4.5 mg/l, 72 hrs) and subsequently injected with E2 (6.75 ng/g dw). Responses were evaluated in CHP, E2 and CHP/E2 treatment groups at 24 h p.i. by a biomarker/transcriptomic approach. CHP and E2 induced additive, synergistic, and antagonistic effects on lysosomal biomarkers (lysosomal membrane stability, lysosome/cytoplasm volume ratio, lipofuscin and neutral lipid accumulation). Additive and synergistic effects were also observed on the expression of estrogen-responsive genes (GSTπ, catalase and 5-HTR) evaluated by RT-Q-PCR. The use of a 1.7K cDNA Mytilus microarray showed that CHP, E2 and CHP/E2, induced 81, 44, and 65 Differentially Expressed Genes (DEGs), respectively. 24 genes were exclusively shared between CHP and CHP/E2, only 2 genes between E2 and CHP/E2. Moreover, 36 genes were uniquely modulated by CHP/E2. Gene ontology annotation was used to elucidate the putative mechanisms involved in the responses elicited by different treatments. Conclusions: The results show complex interactions between CHP and E2 in mussel digestive gland, indicating that the combination of certain pesticides and hormones may give rise to unexpected effects at the molecular/cellular level. Overall, these data demonstrate that CHP can interfere with the mussel responses to natural estrogens. Four-condition experiment. Dual color competitive hybridizations. Common reference (vehicle treated animals, 0.02% Dimethyl sulfoxide, injected with 50 μl of a solution of Artificial Sea Water containing 0.05 % ethanol); Pools of six animals. Biological replicates: 4 controls, 4 Chlorpyrifos, 4 17β-estradiol, 4 Chlorpyrifos-17β-stradiol. One replicate per array.
2011-12-31 | E-GEOD-26222 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE24229: C. elegans : Control vs. Chlorpyrifos (0.5mg/l) treatment GSE24230: C. elegans : Control vs. Diazinon (0.5mg/l) treatment GSE24254: C. elegans : Control vs. Chorpyrifos (0.5mg/l) + Diazinon (1 mg/l) treatment Refer to individual Series
2011-07-31 | E-GEOD-24257 | biostudies-arrayexpress