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Progestins alter hormone homeostasis and may result in reproductive effects in humans and animals. Thus far, studies in fish have focused on the hypothalamic-pituitary-gonadal (HPG)-axis and reproduction, but other effects have little been investigated. Here we report that progesterone (P4) and drospirenone (DRS) interfere with regulation of the circadian rhythm in fish. Breeding pairs of adult zebrafish were exposed to P4 and DRS at concentrations between 7 and 13 650 ng/L for 21 days. Transcriptional analysis revealed significant and dose-dependent alterations of the circadian rhythm network in the brain with little effects in the gonads. Significant alterations of many target transcripts occurred even at environmental relevant concentrations of 7 ng/L P4 and at 99 ng/L DRS. They were fully consistent with the well-described circadian rhythm negative/positive feedback loops. Transcriptional alterations of the circadian rhythm network were correlated with those in the HPG-Liver-axis. Fecundity was decreased at 742 (P4) and 2763 (DRS) ng/L. Dose-dependent alterations in the circadian rhythm network were also observed in F1 eleuthero-embryos. Our results suggest a potential target of environmental progestins, the circadian rhythm network, in addition to the adverse reproductive effects. Forthcoming studies should show whether the transcriptional alterations in circadian rhythm translate into physiological effects. [ABSTRACT FROM AUTHOR]

Medroxyprogesterone acetate (MPA) and dydrogesterone (DDG) are synthetic progestins widely used in human and veterinary medicine. Although aquatic organisms are exposed to them through wastewater and animal farm runoff, very little is known about their effects in the environment. Here we provide a comprehensive analysis of the responses of zebrafish (Danio rerio) to MPA, DDG, and their binary mixtures at measured concentrations between 4.5 and 1663 ng/L. DDG and both mixtures impaired reproductive capacities (egg production) of breeding pairs and led to histological alterations of ovaries and testes and increased gonadosomatic index. Transcriptional analysis of up to 28 genes belonging to different pathways demonstrated alterations in steroid hormone receptors, steroidogenesis enzymes, and specifically, the circadian rhythm genes, in different organs of adult zebrafish and eleuthero-embryos. Alterations occurred even at environmentally relevant concentrations of 4.5-4.8 ng/L MPA, DDG and the mixture in eleuthero-embryos and at 43-89 ng/L in adult zebrafish. Additionally, the mixtures displayed additive effects in most but not all parameters in adults and eleuthero-embryos, suggesting concentration addition. Our data suggest that MPA and DDG and their mixtures induce multiple transcriptional responses at environmentally relevant concentrations and adverse effects on reproduction and gonad histology at higher levels. [ABSTRACT FROM AUTHOR]

A listing of "priority pharmaceuticals" for human use in Italy resulted in the selection of 26 pharmaceuticals, belonging to 11 therapeutic classes. They were analyzed by liquid chromatography-tandem mass spectrometry, their occurrence was assessed in six sewage treatment plants (STPs), and the loads and the removal rates (RR) were studied. Total loads ranged from 1.5 to 4.5 g/day/1000 inhabitants in influents and 1.0 and 3.0 g/day/1000 inhabitants in effluents. Total RR in STPs were mostly lower than 40%. Pharmaceuticals could be divided into three groups according to their behavior in STPs: one group with RR higher in summer than in winter, one group with RR similar in summer and winter, and a last group not removed. Last, we studied the distribution and fate of residual pharmaceuticals in the surface waters receiving the effluents of the STPs and identified degradation and sorption as the major factors affecting attenuation. Ciprofloxacin, ofloxacin, sulfamethoxazole (antibiotics), atenolol (cardiovascular drug), ibuprofen (antiinflammatory), furosemide, hydrochlorothiazide (diuretics), ranitidine (gastrointestinal drug), and bezafibrate (lipid regulator) were the most abundant residual drugs, thus those of environmental concern. [ABSTRACT FROM AUTHOR]