Single cell RNA-seq reveals that granulosa cells are a target of phthalate toxicity in the ovary
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ABSTRACT:
PROVIDER: PRJNA1160814 | ENA |
REPOSITORIES: ENA
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| SRR30659385.fastq.gz | Fastqsanger.gz |
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Project description:Phthalate esters (PAEs), a notable plasticizer, could be prolific contaminants in the aquatic environment, and have been shown to induce reproductive toxicity. However, studies concerning the toxicity towards aquatic species are based upon individual chemicals and the combined toxicity of PAEs to aquatic organisms remains unclear. The aim of this study was to explore the potential toxic mechanism of combined exposure to dibutyl phthalate (DBP) and diisobutyl phthalate (DiBP) in adult female zebrafish ovarian. Zebrafish were exposed to DBP, DiBP and their mixtures for 30 days, and their effects on ovarian histology, plasma sex hormones and ovarian transcriptomics were investigated. The plasma estradiol (E2) levels were significantly decreased 38.9% for DBP-1133 exposure group and 41.0% for DiBP-1038 exposure group. The percentages of late/mature oocyte were also significantly decreased 17.3% in DBP-1133 exposure and 16.2% in DiBP-1038 exposure, while those in combined exposure were not significantly affected. Nonetheless, transcriptome sequencing discovered 2564 differential expressed genes (DEGs) in zebrafish ovary after exposure to the mixtures. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis identified that those DEGs were involved in the neuroactive ligand-receptor interaction, GnRH, progesterone-mediated oocyte maturation, oocyte meiosis and steroid hormone biosynthesis signaling pathways. These results revealed that combined exposure showed potential reproductive toxicity at the molecular level.
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Project description:Transcriptomic analysis reveals potential mechanisms of toxicity in a combined exposure to dibutyl phthalate and diisobutyl phthalate in zebrafish (Danio rerio) ovary
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Project description:Aquatic organisms are generally exposed to a mixture of phthalate esters (PAEs) that have been shown to induce reproductive toxicity. However, their potential toxicity mechanisms to aquatic organisms remain unclear. Here male zebrafish were exposed to dibutyl phthalate (DBP), diisobutyl phthalate (DiBP) and their mixtures for 30 days, and their effects on plasma sex hormones, testis histology and testis transcriptomics were investigated. DBP, DiBP and their mixtures could induce the disequilibrating ratio of testosterone (T) and plasma estradiol (E2) in plasma. The percentage of spermatozoa (Sz) was significantly decreased by 30.6% under DBP-1133 exposure and 27.8% under Mix-3 exposure, and widen intercellular spaces appeared under DiBP-1038 exposure. Transcriptome sequencing revealed 2795 differentially expressed genes (DEGs) in the DBP-1133 exposure group, 1613 DEGs in the DiBP-1038 exposure group and 4570 DEGs in the Mix-3 exposure group, indicating that the toxicity of combined exposure was higher than that of single exposure. Cytokine-cytokine receptor interaction was associated with the toxicity mechanism of DBP, DiBP and Mix. While GnRH signaling pathway and MAPK signaling pathway were related to the toxicity mechanism of DBP. ECM-receptor interaction, steroid hormone biosynthesis, retinol metabolism and PPAR signaling pathway were associated with the toxicity mechanism of DiBP and Mix.
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