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

ABSTRACT: 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.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE48802 | GEO | 2013/07/12

SECONDARY ACCESSION(S): PRJNA211816

REPOSITORIES: GEO

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

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

Identification of Rat foreskin biomarkers of in utero dibutyl phthalate exposure

2013-06-04 | E-GEOD-47618 | biostudies-arrayexpress

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

2013-07-12 | E-GEOD-48802 | biostudies-arrayexpress

Rattus norvegicus

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

| PRJNA134305 | ENA

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.

2011-04-25 | E-GEOD-25196 | biostudies-arrayexpress

Microarray analysis of rat testis following combined fetal and postnatal DBP exposure

Project description:Provided later Pregnant Fisher 344 rats will be purchased from Charles River Laboratories, Inc. and delivered to CIIT on gestational day (GD) 7 (GD0 = day first vaginal plug positive). At gestational day 12 (GD12), the dams will be exposed once/day until GD20 to 50 mg/kg dibutyl phthalate (DBP) in corn oil vehicle via oral gavage. Each dose group will contain 4-6 vehicle control or phthalate treated dams. Groups of animals will be sacrificed at GD20, postnatal day (PND) 35, and PND90 for endpoint analysis. At GD20, treated and control animals will be examined for various endpoints including body weight, testicular histopathology, gene expression profile via microarray analysis, and anogenital distance (AGD). AGD (at parturition; PND1) and nipple number/location (at PND14 and day of sacrifice) will be determined on animals in the postnatal groups. At PND35 or 90, one male from each in utero corn oil vehicle or DBP exposed group will receive a second gavage of either corn oil or 500 mg/kg DBP. 6 hours after the second gavage, the following endpoints will be examined: 1) testis histopathology; 2) spermatid head quantification (PND90 only); 3) testis and body weights; 5) genome-wide gene expression (via microarray); and 6) germ cell apoptosis (TUNEL assay).

2008-11-24 | E-GEOD-13550 | biostudies-arrayexpress

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

2011-04-25 | GSE25196 | GEO

Microarray analysis of MEHP gavaged PND28 male rats

Project description:In rodent models, phthalate exposure alters both the fetal and pubertal testis, but the resulting histopathological changes are divergent. This suggests that the underlying molecular and cellular phthalate mechanism may be age-dependent. Using genome-wide expression profiling of acutely-exposed rats, the initial molecular response in pubertal rat testis following in vivo phthalate exposure was determined. For this study, postnatal day 28 rats were exposed to a single dose of 1 g/kg mono-(2-ethyl)hexyl phthalate (MEHP) and assayed at 1, 2, 3, 6, and 12 hrs thereafter using Affymetrix Rat Genome 230 2.0 Arrays. Keywords: Time course, single dose

2006-04-01 | GSE4514 | GEO

Testicular dysgenesis syndrome and long-lasting epigenetic silencing of mouse sperm genes involved in the reproductive system after prenatal exposure to DEHP

Project description:Prenatal exposure to 300 mg/kg/day of bis(2-ethylhexyl)phthalate (D300) was administered to pregnant mice during embryonic days 9th to 19th, inducing a Testicular Dysgenesis Syndrome (TDS), observed in 100 days old F1 derived C57BL/6J males. A transcriptomic analysis was performed from spermatozoa produced by D300 mice compared with CTL. We used an adapted RNAseq method able to quantify all RNAs molecules independently of the 5’ and 3’ modifications.

2017-01-09 | GSE86837 | GEO

Effects of DEHP on the hepatic expression of a selection of mouse genes related to nuclear receptor signaling.

Project description:Phthalates are industrial additives widely used as plasticizers. In addition to deleterious effects on male genital development, population studies have documented correlations between phthalates exposure and impacts on reproductive tract development and on the metabolic syndrome in male adults. In this study we investigated potential mechanisms underlying the impact of di-(2-ethylhexyl)-phthalate (DEHP) on adult mouse liver in vivo. A parallel analysis of hepatic transcript and metabolic profiles from adult mice exposed to varying DEHP doses was performed. Hepatic genes modulated by DEHP are predominantly PPARÎ± targets. However, the induction of prototypic cytochrome P450 genes strongly supports the activation of additional NR pathways, including Constitutive Androstane Receptor (CAR). Integration of transcriptomic and metabonomic profiles revealed a correlation between the impacts of DEHP on genes and metabolites related to heme synthesis and on the Rev-erbÎ± pathway that senses endogenous heme level. Keywords: Treatment effect One-color macroarrays, 4 experimental conditions: Control mice (vehicle treated), mice treated with di-(2-ethylhexyl)-phthalate (DEHP) at 30 mg/kg/day (D30), 180 mg/kg/day (D180) or 1100 mg/kg/day (D1100) for 14 days, Biological replicates: 6 controls, 4 D30, 4 D180, 5 D1100, One replicate per array

2010-05-05 | E-GEOD-14629 | biostudies-arrayexpress

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