Bisphenol A Analogues Induce Neuroendocrine Disruption via Gut-Brain Regulation in Zebrafish.
Environ Sci Technol
; 58(2): 1022-1035, 2024 Jan 16.
Article
em En
| MEDLINE
| ID: mdl-38165294
ABSTRACT
There is epidemiological evidence in humans that exposure to endocrine-disrupting chemicals such as bisphenol A (BPA) is tied to abnormal neuroendocrine function with both behavioral and intestinal symptoms. However, the underlying mechanism of this effect, particularly the role of gut-brain regulation, is poorly understood. We exposed zebrafish embryos to a concentration series (including environmentally relevant levels) of BPA and its analogues. The analogue bisphenol G (BPG) yielded the strongest behavioral impact on zebrafish larvae and inhibited the largest number of neurotransmitters, with an effective concentration of 0.5 µg/L, followed by bisphenol AF (BPAF) and BPA. In neurod1EGFP transgenic zebrafish, BPG and BPAF inhibited the distribution of enteroendocrine cells (EECs), which is associated with decreased neurotransmitters level and behavioral activity. Immune staining of ace-α-tubulin suggested that BPAF inhibited vagal neural development at 50 and 500 µg/L. Single-cell RNA-Seq demonstrated that BPG disrupted the neuroendocrine system by inducing inflammatory responses in intestinal epithelial cells via TNFα-trypsin-EEC signaling. BPAF exposure activated apoptosis and inhibited neural developmental pathways in vagal neurons, consistent with immunofluorescence imaging studies. These findings show that both BPG and BPAF affect the neuroendocrine system through the gut-brain axis but by different mechanisms, revealing new insights into the modes of bisphenol-mediated neuroendocrine disruption.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenóis
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Peixe-Zebra
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Sistemas Neurossecretores
Limite:
Animals
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Humans
Idioma:
En
Revista:
Environ Sci Technol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China