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Dose-dependent effects of dibutyl phthalate on embryonic development in zebrafish (Danio rerio): The value of integrating concentration gradients in transcriptomic analyses

ABSTRACT: This study investigates the effects of dibutyl phthalate (DBP)—a plasticizer commonly detected in surface waters worldwide—on zebrafish (Danio rerio) embryos exposed to a concentration gradient from 0 to 120 hours post-fertilization (’protuding mouth’ stage). The primary objective was to assess the utility of integrating concentration gradients into transcriptomic analyses to uncover the mechanisms of action of environmental contaminants, such as DBP. Using this experimental design, dose-response modelling was applied to estimate the sensitivity and shape of transcriptomic responses across the DBP gradient. Following optimized over-representation analysis, we revealed that the retinoid signaling pathway may be the most sensitive pathway affected by DBP during zebrafish development, potentially leading to significant morphological changes.

ORGANISM(S): Danio rerio

PROVIDER: GSE283957 | GEO | 2024/12/18

REPOSITORIES: GEO

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Transcriptomic analysis reveals potential mechanisms of toxicity in a combined exposure to dibutyl phthalate and diisobutyl phthalate in zebrafish (Danio rerio) ovary

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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Fetal Rat Testis mRNA Expression after 50 mg/kg Dibutyl Phthalate Exposure

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Fetal Rat Testis mRNA Expression after 50 mg/kg Dibutyl Phthalate Exposure

Project description:High dose level dibutyl phthalate (DBP) exposure of fetal rat testes in vivo inhibits testosterone production (i.e. endocrine disruption). Here, fetal testis mRNA levels were profiled following exposure to a DBP dose level that did not significantly reduce testosterone levels. The goal was to identify the constellation of gene expression changes that do not correlate with endocrine disruption. Fischer 344 rats were exposed via oral gavage of the dam to vehicle (corn oil) or 50 mg/kg (body weight) DBP daily from gestational day (GD) 12 to 20. The day after mating was defined as gestational day 0. Six hours after the final exposure on GD20, fetal testes were dissected and mRNA levels quantified using Affymetrix Rat Expression 230 2.0 microarrays.

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Evaluation of the potential toxicity mechanism of single and combined exposure of dibutyl phthalate and diisobutyl phthalate to zebrafish (Danio rerio) testis based on transcriptomic analysis

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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Identification of Rat foreskin biomarkers of in utero dibutyl phthalate exposure [Illumina]

Project description:Dibutyl phthalate was administered to pregnant Sprague Dawley rats from gestational days 16-20 at either a 100 mg/kg/day or 500 mg/kg/day dose level. This timeframe covers the reproductive masculinization window which corresponds to increased androgen signalling. Dibutyl phthalate has been shown to disrupt testosterone production leading to male reproductive abnormalities. As such, we selected this exposure window for our study and examined gene expression changes in the male rat foreskin, which expresses the androgen receptor. We collected tissue samples at both gestational day 20 to identify gene expression changes immediately after exposure, and postnatal day 5 to identify gene expression changes persisting after birth using microarray analysis (Illumina RatRef 12 Bead Chips). To determine whether gene expression changes were brought on by decreased androgen signalling or additional effects of dibutyl phthalate exposure, we exposed rats to the potent androgen receptor antagonist flutamide (5 mg/kg/day) during the same period of development. Gene expression changes were compared to determine which were brought on by disruption of androgen signalling and which were the result of other aspects of chemical exposure.

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Identification of Rat foreskin biomarkers of in utero dibutyl phthalate exposure [Illumina]

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Dose-dependent effects of dibutyl phthalate on embryonic development in zebrafish (Danio rerio): The value of integrating concentration gradients in transcriptomic analyses

Project description:Dose-dependent effects of dibutyl phthalate on embryonic development in zebrafish (Danio rerio): The value of integrating concentration gradients in transcriptomic analyses

| PRJNA1196384 | ENA

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