PUBLICATION
Genetic and Epigenetic Evidence for Nonestrogenic Disruption of Otolith Development by Bisphenol A in Zebrafish
- Authors
- Yuan, M., Zeng, C., Lu, H., Yue, Y., Sun, T., Zhou, X., Li, G., Ai, N., Ge, W.
- ID
- ZDB-PUB-231002-124
- Date
- 2023
- Source
- Environmental science & technology 57(43): 16190-16205 (Journal)
- Registered Authors
- Ai, Nana, Ge, Wei, Lu, Huijie
- Keywords
- CRISPR/Cas9, bisphenol A, epigenetics, otolith malformation, zebrafish
- MeSH Terms
-
- Animals
- Benzhydryl Compounds/toxicity
- Endocrine Disruptors*/metabolism
- Endocrine Disruptors*/toxicity
- Epigenesis, Genetic
- Otolithic Membrane
- Phenols/toxicity
- Zebrafish*/genetics
- PubMed
- 37752410 Full text @ Env. Sci. Tech.
Citation
Yuan, M., Zeng, C., Lu, H., Yue, Y., Sun, T., Zhou, X., Li, G., Ai, N., Ge, W. (2023) Genetic and Epigenetic Evidence for Nonestrogenic Disruption of Otolith Development by Bisphenol A in Zebrafish. Environmental science & technology. 57(43):16190-16205.
Abstract
Bisphenol A (BPA) is a well-known endocrine-disrupting chemical (EDC) that has estrogenic activities. In addition to disrupting reproductive development and function via estrogenic signaling pathways, BPA can also interfere with nonreproductive functions through nonestrogenic pathways; however, the mechanisms underlying such nonestrogenic activities are not well understood. In this study, we demonstrated that BPA could disrupt otolith formation during the early development of zebrafish with long-lasting ethological effects. Using multiple mutants of estrogen receptors, we provided strong genetic evidence that the BPA-induced otolith malformation was independent of estrogen signaling. Transcriptome analysis revealed that two genes related to otolith development, otopetrin 1 (otop1) and starmaker (stm), decreased their expression significantly after BPA exposure. Knockout of both otop1 and stm genes could phenocopy the BPA-induced otolith malformation, while microinjection of their mRNAs could rescue the BPA-induced abnormalities of otolith formation. Further experiments showed that BPA inhibited the expression of otop1 and stm by activating the MEK/ERK-EZH2-H3K27me3 signaling pathway. Taken together, our study provided comprehensive genetic and molecular evidence that BPA induced the otolith malformation through nonestrogenic pathway during zebrafish early development and its activities involved epigenetic control of key genes (e.g., otop1 and stm) participating in otolith formation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping