PUBLICATION

Developmental exposure to Pb2+ induces transgenerational changes to zebrafish brain transcriptome

Authors
Meyer, D.N., Crofts, E.J., Akemann, C., Gurdziel, K., Farr, R., Baker, B.B., Weber, D., Baker, T.R.
ID
ZDB-PUB-191212-15
Date
2019
Source
Chemosphere   244: 125527 (Journal)
Registered Authors
Weber, Dan
Keywords
Endocrine homeostasis, Epigenetics, Lead (Pb(2+)), Neurodevelopment, Transgenerational, Zebrafish
MeSH Terms
  • Animals
  • Brain/metabolism*
  • Endocrine System/metabolism
  • Epigenesis, Genetic/drug effects
  • Female
  • Inheritance Patterns/drug effects
  • Lead/pharmacology*
  • Male
  • Transcriptome/drug effects*
  • Zebrafish/genetics*
  • Zebrafish/growth & development
  • Zebrafish/metabolism
PubMed
31816550 Full text @ Chemosphere
Abstract
Lead (Pb2+) is a major public health hazard for urban children, with profound and well-characterized developmental and behavioral implications across the lifespan. The ability of early Pb2+ exposure to induce epigenetic changes is well-established, suggesting that Pb2+-induced neurobehavioral deficits may be heritable across generations. Understanding the long-term and multigenerational repercussions of lead exposure is crucial for clarifying both the genotypic alterations behind these behavioral outcomes and the potential mechanism of heritability. To study this, zebrafish (Danio rerio) embryos (<2 h post fertilization; EK strain) were exposed for 24 h to waterborne Pb2+ at a concentration of 10 μM. This exposed F0 generation was raised to adulthood and spawned to produce the F1 generation, which was subsequently spawned to produce the F2 generation. Previous avoidance conditioning studies determined that a 10 μM Pb2+ dose resulted in learning impairments persisting through the F2 generation. RNA was extracted from control- and 10 μM Pb2+-lineage F2 brains, (n = 10 for each group), sequenced, and transcript expression was quantified utilizing Quant-Seq. 648 genes were differentially expressed in the brains of F2 lead-lineage fish versus F2 control-lineage fish. Pathway analysis revealed altered genes in processes including synaptic function and plasticity, neurogenesis, endocrine homeostasis, and epigenetic modification, all of which are implicated in lead-induced neurobehavioral deficits and/or their inheritance. These data will inform future investigations to elucidate the mechanism of adult-onset and transgenerational health effects of developmental lead exposure.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping