Transcriptional and histological alterations in gonad of adult zebrafish after exposure to the synthetic progestin norgestrel

The aim of the present study was to investigate the effects of norgestrel (NGT) on gonadal development in adult zebrafish. Adult zebrafish were exposed to NGT for 14 d at 871ngL(-1) for microarray analysis, and a follow-up experiment was conducted to further study the targeted pathway in adult zebrafish after exposure to NGT at 6.7, 83, and 912ngL(-1) by quantitative polymerase chain reaction (qPCR) and histological analysis. The microarray analysis revealed that 11545 transcripts were identified. Gene ontology analysis showed organ development, system development, multicellular organismal development, single-organism developmental process, and developmental process were significantly enriched. A Venn diagram displayed 434 target genes involved in organ development, and these genes were common in these 5 development-related processes. Kyoto Encyclopedia of Genes and Genomes analysis showed that the notch signaling pathway was the top toxicity pathway, and it was selected as the target pathway for further qPCR analysis. The qPCR analysis revealed significant and dose-dependent alterations of most target genes involved in the notch signaling pathway in the gonads, even at an environmentally relevant concentration of 6.7ngL(-1). The transcriptional patterns were consistent with the notch signaling cascade. In addition, NGT significantly increased the frequency of mature sperm and decreased the frequency of immature sperm at all concentrations. Meanwhile, NGT treatment increased the percentage of mature vitellogenic oocytes and atretic follicles at 912ngL(-1) but decreased the percentage of immature vitellogenic oocytes. Thus, the present study demonstrated significant developmental toxicity in the gonad of adult zebrafish even at environmentally relevant NGT concentrations. Environ Toxicol Chem 2017;36:3267-3276. (c) 2017 SETAC