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Transcriptome analysis reveals differences in developmental neurotoxicity mechanism of methyl-, ethyl-, and propyl- parabens in zebrafish embryos

ABSTRACT: Limited studies on comparison of developmental (neuro)toxicity of parabens have been conducted and unharmonized concentrations between phenotypic observations and transcriptomic analysis hamper understanding of their differential molecular mechanism. Developmental toxicity testing was conducted with commonly used methyl- (MtP), ethyl- (EtP) and propyl-paraben (PrP) in zebrafish embryos. Based on benchmark dose 5% (BMD5), embryonic mortality based-point of departure (M-PoD) values of three parabens were determined and changes in locomotor behavior were evaluated at concentrations of 0, M-PoD/50, M-PoD/10, and M-PoD in which transcriptomic analysis was conducted to explore the underlying neurotoxicity mechanism. Higher long-chained parabens were more toxic than short-chained parabens, as determined by M-PoD values of 154.1, 72.6, and 24.2 µM for MtP, EtP, and PrP, respectively. While exposure to EtP resulted in hyperactivity, no behavior effect was observed by MtP and PrP. Transcriptomics analysis revealed that abnormal behaviors in EtP-exposed group are associated with the distinctly enriched pathways in signal, transport, calcium ion binding, and metal-binding. In contrast, exposure to MtP and PrP mainly disrupted the membrane and transmembrane, which are closely linked to abnormal embryonic development rather than neurobehavior changes. According to the changes in expression of signature mRNAs, tentative transcriptomic-based PoD (T-PoD) values for each paraben were determined as MtP (2.68 µM), EtP (3.85 µM), and PrP (1.4 µM).

ORGANISM(S): Danio rerio

PROVIDER: GSE239773 | GEO | 2023/08/07

REPOSITORIES: GEO

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