PUBLICATION

An embryonic 100μg/L lead exposure results in sex-specific expression changes in genes associated with the neurological system in female or cancer in male adult zebrafish brains

Authors
Lee, J., Horzmann, K.A., Freeman, J.L.
ID
ZDB-PUB-171028-10
Date
2018
Source
Neurotoxicology and teratology   65: 60-69 (Journal)
Registered Authors
Freeman, Jennifer
Keywords
DOHaD, Lead, MAPK, Sex differences, Transcriptomics, Zebrafish
Datasets
GEO:GSE78881, GEO:GSE78880, GEO:GSE78879
MeSH Terms
  • Animals
  • Brain/drug effects
  • Brain/embryology
  • Brain/growth & development
  • Embryo, Nonmammalian/drug effects
  • Embryonic Development/drug effects*
  • Embryonic Development/genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental/drug effects*
  • Lead/toxicity*
  • Neoplasms/embryology
  • Neoplasms/genetics*
  • Nervous System Diseases/embryology
  • Nervous System Diseases/genetics*
  • Sex Characteristics*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/growth & development*
PubMed
29074346 Full text @ Neurotoxicol. Teratol.
Abstract
Developmental lead (Pb) exposure is linked to neurological health issues. Results from non-human primate and rodent studies suggest detrimental effects of an early life Pb exposure, showing transcriptional disturbances and pathological evidence of Alzheimer's disease in the adult animal brain. To elucidate the impacts of an embryonic Pb exposure on the adult brain, transcriptomic analysis was completed on the brain of zebrafish aged 12months exposed to a control treatment or to an embryonic 100μg/L Pb exposure by sex. In the adult female zebrafish brain, significant changes in expression profiles occurred in a number of genes involved in neurological disease and nervous system development and function. On the other hand, in adult males, a number of genes with significant expression alterations were found to be associated with cancer and tumors. p38 mitogen-activated protein kinase (p38 MAPK) was also indicated as an upstream regulator of observed gene expression changes. Western blot analysis confirmed activation of p38 MAPK in the form of phosphorylated p38 MAPK in the male zebrafish brain. In addition, we compared transcriptomic changes observed in this study to a previous study with an embryonic exposure of 10μg/L Pb by sex, showing unique sets of genes dependent on Pb concentration. Overall, these results show sex-specific and concentration-dependent disturbances of global gene expression patterns in the brain of adult zebrafish exposed to Pb during embryogenesis.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes