Unknown,Transcriptomics,Genomics,Proteomics

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Effects of 35 days oral exposure of adult female Sprague-Dawley rats to p-tert-octylphenol on uterine gene expression

ABSTRACT: Contamination of the environment with endocrine disrupting chemicals (EDCs) has raised concerns about potential health hazards for humans and wildlife. P-tert-octylphenol (OP) is one such ubiquitous chemical reported to bind to the estrogen receptor (ER) and alter expression of estrogen-responsive genes. Human and wildlife exposure to OP are likely, due to its persistence in the environment and its presence in food, water and items of daily use. Detrimental effects of OP exposures on the reproductive system have been observed in some, but not all, in vivo experiments. This study compared estrogenic effects of OP in vitro with those in vivo in adult female rats, attempting to better mimic real-life exposures in adults. In vitro, OP bound to human ER weakly and accelerated proliferation of MCF-7 cells. Adult Sprague-Dawley rats were given OP by gavage either once (125 mg/kg OP) or daily for 35 days (25, 50, 125 mg/kg). Body and organ weights and ovarian follicle populations were unaltered in OP-exposed adult rats after either time point, despite detectable levels of OP in reproductive organs. Toxicity of OP was demonstrated by a slightly reduced growth rate and slightly altered estrous cycle, but there were no significant estrogen-like changes in histomorphology or microarray analyses of gene expression of uterine tissue. Prepubertal rats exposed by gavage to 125 or 250 mg/kg OP for three days failed to show any uterotrophic effects, although E2 caused a 3-fold increase in uterine weight. These results do not support a dose-dependent, estrogenic mode of action for OP. Keywords: treatment vs control Individual uterine RNA samples from 4 female 35-day old rats per treatment (4 OP and 4 vehicle) sacrificed on the second day of diestrus after 35 days of exposure to OP (125 mg/kg/day in propylene glycol) or solvent (propylene glycol, PG) by gavage were compared with liver RNA pooled from all 8 rats (as reference, combined OP and solvent treatment groups). Comparisons were made between treatments. Liver cDNA was always marked with Cy5 and uterine cDNA was always marked with Cy3.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Patrick Devine

PROVIDER: E-GEOD-14528 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Contamination of the environment with endocrine disrupting chemicals (EDCs) has raised concerns about potential health hazards for humans and wildlife. P-tert-octylphenol (OP) is one such ubiquitous chemical reported to bind to the estrogen receptor (ER) and alter expression of estrogen-responsive genes. Human and wildlife exposure to OP are likely, due to its persistence in the environment and its presence in food, water and items of daily use. Detrimental effects of OP exposures on the reproductive system have been observed in some, but not all, in vivo experiments. This study compared estrogenic effects of OP in vitro with those in vivo in adult female rats, attempting to better mimic real-life exposures in adults. In vitro, OP bound to human ER weakly and accelerated proliferation of MCF-7 cells. Adult Sprague-Dawley rats were given OP by gavage either once (125 mg/kg OP) or daily for 35 days (25, 50, 125 mg/kg). Body and organ weights and ovarian follicle populations were unaltered in OP-exposed adult rats after either time point, despite detectable levels of OP in reproductive organs. Toxicity of OP was demonstrated by a slightly reduced growth rate and slightly altered estrous cycle, but there were no significant estrogen-like changes in histomorphology or microarray analyses of gene expression of uterine tissue. Prepubertal rats exposed by gavage to 125 or 250 mg/kg OP for three days failed to show any uterotrophic effects, although E2 caused a 3-fold increase in uterine weight. These results do not support a dose-dependent, estrogenic mode of action for OP. Keywords: treatment-control Individual uterine RNA samples from 4 female ~35-day old rats per treatment (4 OP and 4 vehicle) sacrificed on the second day of diestrus after a single dose of OP (125 mg/kg/day in propylene glycol) or solvent (propylene glycol, PG) by gavage on the first day of diestrus were compared with liver RNA pooled from all 8 rats (as reference, combined OP and solvent treatment groups). Comparisons were made between treatments. Liver cDNA was always marked with Cy5 and uterine cDNA was always marked with Cy3.

Project description:Background: Post-menopausal obesity is an established risk factor for breast cancer. Consumption of diets high in fat is known to be highly correlated with obesity. In this, we sought to evaluate the interaction(s) between high fat diet, weight gain and mammary carcinogenesis using an obese-resistant and obese-prone rat model with direct correlates to human disease. Methods: Female obese-prone (OP) and obese-resistant (OR) weanling rats were placed on either a low fat (10% kcal) or a high fat (39% kcal) n-6 polyunsaturated (PUFA) safflower diet for 30 days. At post natal day (PND) 50, global gene expression profiling was performed on microdissected mammary epithlelium from one cohort of rats and another cohort of rats were given a single oral gavage of either 7,12-dimethylbenz[a]anthracene (DMBA at 14 mg/kg) or vehicle. Rats were then maintained on the diets and body weights, food consumption and development of mammary lesions were monitored weekly. Results: The DMBA-treated OR rats on the 39% safflower diet had significantly greater incidence of ductal carcinoma-in-situ (DCIS) lesions and significantly greater DCIS multiplicity than DMBA-treated OR rats on the 10% safflower diet. These differences were not seen in the OP strain. Gene expression analysis of mammary ductal epithelium from OR rats on the high fat diet showed significant upregulation of proliferation-related genes compared to those consuming the low fat safflower diet. Again, these differences were not seen in the OP strain. Conclusion: Our findings indicate that consumption of high fat safflower diet enhances mammary carcinogenesis in an OR rat strain through increased proliferation of mammary epithelium at the time of exposure, but not in the OP rat strain. Thus, the diet-induced increase in sensitivity was strain-specific and independent of weight gain or obesity level. Female obese-prone (OP) and obese-resistant (OR) weanling rats were placed on either a low fat (10% kcal) or a high fat (39% kcal) n-6 polyunsaturated (PUFA) safflower diet for 30 days. At post natal day (PND) 50, global gene expression profiling was performed on microdissected mammary epithlelium from one cohort of rats and another cohort of rats were given a single oral gavage of either 7,12-dimethylbenz[a]anthracene (DMBA at 14 mg/kg) or vehicle. Rats were then maintained on the diets and body weights, food consumption and development of mammary lesions were monitored weekly.

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Effects of 35 days oral exposure of adult female Sprague-Dawley rats to p-tert-octylphenol on uterine gene expression

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