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Publikation Reproductive and transcriptional effects of the antiandrogenic progestin chlormadinone acetate in zebrafish (Danio rerio)(Elsevier, 2017) Zhang, Kun; Fent, Karl; Siegenthaler, Patricia Franziska; Zhao, YanbinChlormadinone acetate (CMA) is a frequently used progestin with antiandrogenic activity in humans. Residues may enter the aquatic environment but potential adverse effects in fish are unknown. While our previous work focused on effects of CMA in vitro and in zebrafish eleuthero-embryos, the present study reports on reproductive and transcriptional effects in adult female and male zebrafish (Danio rerio). We performed a reproductive study using breeding groups of zebrafish. After 15 days of pre-exposure, we exposed zebrafish to different measured concentrations between 6.4 and 53,745 ng/L CMA for 21 days and counted produced eggs daily to determine fecundity. Additionally, transcriptional effects of CMA in brains, livers, and gonads were analyzed. CMA induced a slight but statistically significant reduction in fecundity at 65 ng/L and 53,745 ng/L compared to pre-exposure. Furthermore, we observed differential expression for gene transcripts of steroid hormone receptors, genes related to the hypothalamic-pituitary-gonadal axis, and steroidogenesis. In particular, we found a significant decrease of transcript levels of vitellogenin (vtg1) in ovaries and liver, and of cyp2k7 in the liver of males, as well as a significant increase of transcripts of the progesterone receptor (pgr) in testes, and cyp2k1 in the liver of females. The observed effects were weaker than those of other very potent progestins, which is probably related to the lack of interaction of CMA with the zebrafish progesterone receptor.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Regulation of zebrafish (Danio rerio) locomotor behavior and circadian rhythm network by environmental steroid hormones(Elsevier, 01/2018) Fent, Karl; Zhao, Yanbin; Zhang, KunEnvironmental 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.01A - Beitrag in wissenschaftlicher Zeitschrift