Fetal Rat Testis mRNA Expression after 50 mg/kg Dibutyl Phthalate Exposure
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE25196 | GEO | 2011/04/25
SECONDARY ACCESSION(S): PRJNA134305
REPOSITORIES: GEO
Similar Datasets
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.
2011-04-25 | E-GEOD-25196 | biostudies-arrayexpress
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. Two foreskin samples per litter were pooled for gene expression microarray analysis using the Illumina ratRef-12 v1.0 expression beadchip.
2013-07-12 | E-GEOD-48802 | biostudies-arrayexpress
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.
2013-07-12 | GSE48802 | GEO
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.
2013-06-04 | GSE47618 | GEO
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. The flutamide exposure study consisted of seven control dams administered corn oil and seven dams treated with 5 mg/kg/day flutamide. Two foreskin samples per litter were pooled for gene expression microarray analysis using the Affymetrix Gene 1.0 ST Array.
2013-06-04 | E-GEOD-47618 | biostudies-arrayexpress
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.
2021-09-30 | GSE136994 | GEO
Project description: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.
2024-12-18 | GSE283957 | GEO
Project description:Despite the involvement of several serine hydrolases (SHs) in the metabolism of xenobiotics such as dibutyl phthalate (DBP), no study has focused on mapping this enzyme class in zebrafish, a model organism frequently used in ecotoxicology. Here, we survey and identify active SHs in zebrafish larvae and search for biological markers of SH type after exposition to DBP. Zebrafish were exposed to 0, 5, and 100 µg/L DBP from 4 to 120 h post-fertilization. A significant decrease in vitellogenin expression level of about 2-fold compared to the control was found in larvae exposed to 100 µg/L DBP for 120h. The first comprehensive profiling of active SHs in zebrafish proteome was achieved with an activity-based protein profiling (ABPP) approach. Among 49 SHs identified with high confidence, one was the carboxypeptidase ctsa overexpressed in larvae exposed to 100 µg/L DBP for 120h. To the best of our knowledge, this is the first time that a carboxypeptidase has been identified as deregulated following exposure to DBP. The overall results indicate that targeted proteomics approaches such as ABPP can therefore be an asset for understanding the mechanism of action related to xenobiotics in ecotoxicology.
2023-03-11 | PXD038229 | Pride
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.
2019-08-27 | GSE134345 | GEO
Project description:The goal of this study was to determine the effects of a well-characterized anti-androgen, abiraterone acetate, and a suspected human anti-androgen, di-n-butyl phthalate (DBP) on the androgenic function of human fetal testis. Human fetal testis was xenografted into the renal subcapsular space of castrated male athymic nude mice. Hosts were treated with hCG to stimulate testosterone production in the xenografts, and were concurrently treated with either abiraterone acetate or DBP. While abiraterone acetate (14 d, 75 mg/kg/d p.o.) dramatically reduced testosterone and the weights of androgen-sensitive host organs, DBP (14 d, 500 mg/kg/d p.o.) had no effect on androgenic endpoints. Three paired analyses were performed using the LIMMA package in R (commands lmfit and eBayes), with the Benjamini-Hochberg correction for multiple comparisons (Smyth 2005): vehicle-treated xenografts vs. unimplanted testis (n=5), abiraterone-treated xenografts vs. matched control xenografts (n=3), and DBP-treated xenografts vs. matched control xenografts (n=3). There were significant differences in gene expression between grafted and ungrafted samples, including dramatic upregulation of microRNAs. Gene expression analysis also showed that abiraterone decreased expression of genes related to cell differentiation, while DBP induced expression of oxidative stress response genes and decreased expression of factors related to embryonic development.
2013-10-31 | GSE49244 | GEO