Norethisterone exposure alters the transcriptome of Marine Medaka (Oryzias melastigma) larvae

Abstract

ABSTRACT Norethisterone (NET) is one of the earliest synthetic progestins. Its widespread and long-term use means that NET is often detected on the surface and in groundwater samples, which may cause harm to aquatic organisms. Marine medaka (Oryzias melastigma) is a brackish fish, often used in ecotoxicology studies. In this study, the effect of norethisterone exposure on the transcriptome of marine medaka larvae was analyzed. Larvae were exposed to 10 ng/L NET for 24 h, then RNA-Seq was performed. Exposure to 10 ng/L NET resulted in 306 up-regulated and 516 down-regulated genes. An enrichment analysis revealed that differentially expressed genes (DEGs) were significantly enriched in metabolic and biosynthetic pathways, including DNA replication, proteasome, steroid biosynthesis, and other amino acid metabolism pathways. In the DNA replication pathway, all the DEGs were down-regulated, while in the steroid biosynthesis pathway, sqle, hmgcr, dhcr7, and dhcr24 were down-regulated. Quantitative real-time PCR (qPCR) was used to verify 12 DEGs, confirming that the validity of the RNA-Seq analysis. These results show that even low environmental concentrations of NET can lead to transcription level changes of genes related to fish growth and development, which may have adverse effects on the early development and growth of aquatic organisms. Highlights Transcriptomes from norethisterone-exposed marine medaka larvae were obtained A total of 822 differentially expressed genes were identified Norethisterone affected 155 pathways, including DNA replication.