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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 J Devine   Sukhdeep K Sahambi 

PROVIDER: E-GEOD-14528 | ArrayExpress | 2010-05-05



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