Toxicogenomic profiling in maternal and fetal rodent brains following gestational exposure to chlorpyrifos

Journal Article · Tue Jun 15 04:00:00 EDT 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.03.015· OSTI ID:21460177

Moreira, Estefania G ^[1]; Xiaozhong, Yu; Robinson, Joshua F; Griffith, Willian; Hong, Sung Woo; Beyer, Richard P; Bammler, Theo K ^[1]

---

1. Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States)

Considering the wide variety of effects that have been reported to occur in the developmental neurotoxicity of chlorpyrifos (CP) and the lack of consensus on their dependence of brain acetylcholinesterase (AChE) activity inhibition, we applied microarray technology to explore dose-dependent alterations in transcriptional response in the fetal and maternal C57BL/6 mouse brain after daily gestational exposure (days 6 to 17) to CP (2, 4, 10, 12 or 15 mg/kg, sc). We identified significantly altered genes across doses and assessed for overrepresentation of Gene Ontology (GO) biological processes and KEGG pathways. We further clustered genes based on their expression profiles across doses and repeated the GO/pathways analysis for each cluster. The dose-effect relationship of CP on gene expression, both at the gene and pathway levels was non-monotonic and not necessarily related to brain AChE inhibition. The largest impact was observed in the 10 mg/kg dose group which was also the LOAEL for brain AChE inhibition. In the maternal brain, lower doses (4 mg/kg) influenced GO categories and pathways such as cell adhesion, behavior, lipid metabolism, long-term potentiation, nervous system development, neurogenesis, synaptic transmission. In the fetal brain, lower doses (2 and/or 4 mg/kg) significantly altered cell division, translation, transmission of nerve impulse, chromatin modification, long-term potentiation. In addition, some genes involved in nervous system development and signaling were shown to be specifically influenced by these lower CP doses. Our approach was sensitive and reflected the diversity of responses known to be disrupted by CP and highlighted possible additional consequences of CP neurotoxicity, such as disturbance of the ubiquitin proteasome system.

• OSTI ID: 21460177
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 245; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADHESION
ANIMALS
BIOTECHNOLOGY
BODY
BRAIN
CELL DIVISION
CENTRAL NERVOUS SYSTEM
CHROMATIN
GENES
INHIBITION
LIPIDS
MAMMALS
MICE
MICROARRAY TECHNOLOGY
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
RODENTS
TRANSMISSION
VERTEBRATES