PUBLICATION

Elucidation of possible molecular mechanisms underlying the estrogen-induced disruption of cartilage development in zebrafish larvae

Authors
He, H., Wang, C., Tang, Q., Yang, F., Xu, Y.
ID
ZDB-PUB-180303-11
Date
2018
Source
Toxicology letters   289: 22-27 (Journal)
Registered Authors
Yang, Fan
Keywords
Cartilage defect, Estrogen, Extracellular matrix, RNA deep sequencing, Zebrafish
MeSH Terms
  • Animals
  • Apoptosis/drug effects
  • Bone Development/drug effects
  • Bone Resorption/chemically induced
  • Bone Resorption/metabolism
  • Cartilage/abnormalities
  • Cartilage/drug effects*
  • Cartilage/metabolism
  • Cell Cycle/drug effects
  • Chondrogenesis/drug effects*
  • Collagen/genetics
  • Collagen/metabolism
  • Craniofacial Abnormalities/chemically induced*
  • Craniofacial Abnormalities/metabolism
  • Estrogens/adverse effects*
  • Extracellular Matrix/drug effects
  • Extracellular Matrix/metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental/drug effects*
  • Gene Ontology
  • High-Throughput Nucleotide Sequencing
  • Larva
  • Models, Biological*
  • Signal Transduction/drug effects
  • Teratogens/toxicity*
  • Zebrafish
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
29499231 Full text @ Toxicol. Lett.
CTD
29499231
Abstract
Estrogen can affect the cartilage development of zebrafish; however, the mechanism underlying its effects is not completely understood. Four-day-old zebrafish larvae were treated with 0.8 μM estrogen, the 5 days post fertilization (dpf) zebrafish larvae did not demonstrate obvious abnormalities during development; however, the 6 dpf and 7 dpf larvae exhibited abnormal craniofacial bone development along with craniofacial bone degradation. RNA deep sequencing was performed to elucidate the mechanism involved. Gene Ontology functional and KEGG pathway enrichment analysis of differentially expressed genes (DEGs) showed that the extracellular matrix (ECM), extracellular region, ECM-interaction receptor, focal adhesion, cell cycle, apoptosis, and bone-related signaling pathways were disrupted. In these signaling pathways, the expressions of key genes, such as collagen encoded (col19a1a, col7a1, col7al, col18a1, and col9a3), MAPK signaling pathway (fgf19, fgf6a), TGF-beta signaling pathway (tgfbr1), and cell cycle (cdnk1a) genes were altered. The qRT-PCR results showed that after treatment with 0.8 μM 17-β estradiol (E2), col19a1a, col7a1, col7al, col18a1, col9a3, fgf6a, cdkn1a were downregulated, and fgf19, tgfr1 were upregulated, which were consistent with deep sequencing analysis. Therefore, the effect of estrogen on cartilage development might occur via multiple mechanisms. The study results demonstrate the mechanism underlying the effect of estrogen on cartilage development.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping