2021-04, Zheng, Xuehan, Zhang, Kun, Zhao, Yanbin, Fent, Karl

Circadian rhythms control the life of virtually all organisms. They regulate numerous aspects ranging from cellular processes to reproduction and behavior. Besides the light-dark cycle, there are additional environmental factors that regulate the circadian rhythms in animals as well as humans. Here, we outline the circadian rhythm system and considers zebrafish (Danio rerio) as a representative vertebrate organism. We characterize multiple physiological processes, which are affected by circadian rhythm disrupting compounds (circadian disrupters). We focus on and summarize 40 natural and anthropogenic environmental circadian disrupters in fish. They can be divided into six major categories: steroid hormones, metals, pesticides and biocides, polychlorinated biphenyls, neuroactive drugs and other compounds such as cyanobacterial toxins and bisphenol A. Steroid hormones as well as metals are most studied. Especially for progestins and glucocorticoids, circadian dysregulation was demonstrated in zebrafish on the molecular and physiological level, which comprise mainly behavioral alterations. Our review summarizes the current state of knowledge on circadian disrupters, highlights their risks to fish and identifies knowledge gaps in animals and humans. While most studies focus on transcriptional and behavioral alterations, additional effects and consequences are underexplored. Forthcoming studies should explore, which additional environmental circadian disrupters exist. They should clarify the underlying molecular mechanisms and aim to better understand the consequences for physiological processes.

2018-01, Fent, Karl, Zhao, Yanbin, Zhang, Kun

Environmental exposure of fish to steroid hormones through wastewater and agricultural runoff may pose a health risk. Thus far, ecotoxicological studies have largely been focused on the disruption of the sex hormone system, but additional effects have been poorly investigated. Here we report on the effects of a series of different natural and synthetic steroid hormones on the locomotor behavior and the transcriptional levels of core clock genes in zebrafish eleuthero-embryos (Danio rerio). Of the 20 steroids analyzed, progestins and corticosteroids, including progesterone and cortisol, significantly decreased the locomotor activities of eleuthero-embryos at concentrations as low as 16 ng/L, while estrogens such as 17β-estradiol led to an increase. Consistently, progestins and corticosteroids displayed similar transcriptional effects on core clock genes, which were remarkably different from those of estrogens. Of these genes, per1a and nr1d2a displayed the most pronounced alterations. They were induced upon exposure to various progestins and corticosteroids and could be recovered using the progesterone receptor/glucocorticoid receptor antagonist mifepristone; this, however, was not the case for estrogens and the estrogen receptor antagonist 4-hydroxy-tamoxifen. Our results suggest that steroid hormones can modulate the circadian molecular network in zebrafish and provide novel insights into their mode of actions and potential environmental risks.