PUBLICATION

Exposure to phthalates impaired neurodevelopment through estrogenic effects and induced DNA damage in neurons

Authors
Xu, S., Zhang, H., Pao, P.C., Lee, A., Wang, J., Suen Chan, Y., Manno Iii, F.A.M., Wan Chan, S., Han Cheng, S., Chen, X.
ID
ZDB-PUB-200403-90
Date
2020
Source
Aquatic toxicology (Amsterdam, Netherlands)   222: 105469 (Journal)
Registered Authors
Keywords
Double-Strand DNA break, Estrogen receptor, Estrogenic activity, Neurodevelopment, Neurons, Phthalates, Zebrafish
MeSH Terms
  • Animals
  • Cells, Cultured
  • DNA Breaks, Double-Stranded*
  • Embryo, Nonmammalian/drug effects
  • Embryonic Development/drug effects*
  • Embryonic Development/genetics
  • Endocrine Disruptors/toxicity*
  • Estrogen Receptor Antagonists/pharmacology
  • Humans
  • Neurons/drug effects*
  • Neurons/metabolism
  • Neurons/pathology
  • Phthalic Acids/toxicity*
  • Receptors, Estrogen/genetics*
  • Water Pollutants, Chemical/toxicity*
  • Zebrafish
PubMed
32179334 Full text @ Aquat. Toxicol.
Abstract
Phthalates are commonly used in plastic products in daily life. The endocrine-disrupting effects of phthalates have been widely reported. Accumulating evidence from human cohorts and lab animals indicate exposure to phthalates might impair neurodevelopment. However, the direct causal relationship and mechanism between phthalates with neurodevelopment and neurotoxicity have not been firmly established. We found that phthalates (i.e. DBP, DINP, BBP) disrupted the expression of estrogen receptors (esr1, esr2a, esr2b), and impaired neurogenesis in the brain of zebrafish during embryonic development. Moreover, the abnormal expression of estrogen receptors, especially esr2a, was partly rescued in zebrafish which exposed to phthalates, with the estrogen receptor antagonist tamoxifen. Hence, impaired neurogenesis of zebrafish exposed to phthalates was partly reversed by tamoxifen treatment. Moreover, our results show that induced pluripotent stem cells (iPSC)-derived human neurons exposed to phthalates triggered double-strand DNA breaks in vitro. Overall, this study demonstrates that exposure to phthalates affects neurodevelopment in zebrafish embryos and induces neurotoxicity in human neurons partly through disrupting the expression of estrogen receptors.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping