☆ 4.7 Article

Melatonin protects embryonic development and maintains sleep/wake behaviors from the deleterious effects of fluorene-9-bisphenol in zebrafish (Danio rerio)

JOURNAL OF PINEAL RESEARCH (2019)

期刊

JOURNAL OF PINEAL RESEARCH

卷 66, 期 1, 页码 -

出版社

WILEY

DOI: 10.1111/jpi.12530

关键词

development; fluorene-9-bisphenol; melatonin; sleep/wake behavior; surface tension; zebrafish

类别

Endocrinology & Metabolism Neurosciences Physiology

资金

Special Fund for Basic Research on Scientific Instruments of the Chinese National Natural Science Foundation [61327802, 61127006]
National Basic Research Program (973 program) of China [2015CB856500]
Ph.D Candidate Research Innovation Fund of Nankai University [91822298]

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摘要

Environmental endocrine chemicals have various adverse effects on the development of vertebrates. Fluorene-9-bisphenol (BHPF), a substitute of bisphenol A (BPA), is widely used in commercial production. The effects of BHPF on development and behavior are unclear. Melatonin plays a protective role under many unfavorable conditions. In this study, we investigated the effects of BHPF on the development and behaviors of zebrafish and whether melatonin reverses effects induced by BHPF. Zebrafish embryos were exposed to 0.1, 10, or 1000 nmol/L BHPF with or without 1 mu mol/L melatonin from 2 hours postfertilization to 6 days postfertilization. The results showed that 0.1 and 10 nmol/L BHPF had little effect on development. High-dose BHPF (1000 nmol/L) delayed the development, increased mortality and surface tension of embryonic chorions, caused aberrant expression of the key genes (ntl, shh, krox20, pax2, cmlc2) in early development detected by in situ hybridization, and damaged the CaP motor neurons, which were associated with locomotion ability detected by immunofluorescence. Melatonin addition reversed or weakened these adverse effects of BHPF on development, and melatonin alone increased surface tension as the effects of high-dose BHPF. However, all groups of BHPF exposure triggered insomnia-like behaviors, with increased waking activity and decreased rest behaviors. BHPF acted on the hypocretin (hcrt) system and upregulated the expression of sleep/wake regulators such as hcrt, hcrt receptor (hcrtr), arylalkylamine N-acetyltransferase-2 (aanat2). Melatonin recovered the alternation of sleep/wake behaviors induced by BHPF and restored abnormal gene expression to normal levels. This study showed that high-dose BHPF had adverse effects on early development and induced behavioral alternations. However, melatonin prevented BHPF-induced aberrant development and sleep/wake behaviors.

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Exposure to bisphenol A alternatives bisphenol AF and fluorene-9-bisphenol induces gonadal injuries in male zebrafish

Xiangyu Meng, Shifeng Su, Xiyi Wei, Shangqian Wang, Tao Guo, Junjian Li, Huaidong Song, Mengjing Wang, Zengjun Wang

Summary: We found that BPA, commonly found in household products, is inversely correlated with blood testosterone levels in children. BPA replacements like BHPF and BPAF were found to cause delayed gonadal migration and reduced germ cell lineage in zebrafish larvae. Additionally, these replacements bind strongly to androgen receptors, leading to the downregulation of meiosis-related genes and the overexpression of inflammatory markers. Further research on the toxicological effects of BHPF and BPAF on human health is needed and BPA replacements should be investigated for their anti-estrogenic action.

ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY (2023)