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

The aim of this study was to investigate the effects of Norgestrel (NGT) on the gonadal development in adult zebrafish. Adult zebrafish were exposed to NGT for 14 days at 871 ng L−1 for microarray analysis, and a follow-up experiment was conducted to further study targeted pathway in adult zebrafish after exposure to NGT at 6.7 ng L−1, 83 ng L−1 and 912 ng L−1by quantitative PCR (qPCR) and histology 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. Venn diagram displayed 434 target genes involved in organ development, and these genes were common in these five development related processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that notch signaling pathway was the top toxicity pathway and 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 6.7 ng L−1. The transcriptional patterns were consistent with the notch signaling cascade. In addition, NGT significantly increased the frequency of mature sperms and decreased the frequency of immature sperms at all concentrations. Meanwhile, NGT treatment increased the percentage of mature vitellogenic oocyte and atretic follicles at 912 ng L−1, but decreased the percentage of immature vitellogenic oocyte. Thus this study demonstrated significant developmental toxicity in the gonad of adult zebrafish even at environmentally relevant NGT concentrations. This article is protected by copyright. All rights reserved