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Ovarian gene expression is stable after exposure to trichloroethylene.

ABSTRACT: Exposure of female rats to trichloroethylene (TCE), an environmental toxicant commonly found in ground and surface waters throughout the United States, reduces the fertilizability of oocytes produced by these females compared with oocytes from control females. Localization of cytochrome P450 2E1 and glutathione s-transferase alpha, TCE-metabolizing enzymes, in the ovary suggests TCE metabolism occurs in the ovary. The production of bioactive TCE metabolites in the ovary may alter female reproductive function by altering ovarian gene transcription and/or protein expression and function. The purpose of the present study was to examine ovarian gene transcription after exposure of female rats to 0.45% TCE (v/v) in 3% Tween. Control rats received 3% Tween. Microarray analysis after 1 and 5 days of exposure indicated ovarian gene transcription was maintained during TCE exposure with the possible exception of a very few genes. Although conclusions for these few genes were ambiguous from the microarray analysis due to the minimal but statistically significant reductions, quantitative real time RT-PCR (qRT-PCR) analysis indicated expression of these genes was unaltered after TCE exposure. Protein analysis confirmed qRT-PCR results. This study suggests TCE-induced reductions in oocyte fertilizability are independent of currently detectable alterations in ovarian gene expression.

SUBMITTER: Wu KL

PROVIDER: S-EPMC2747470 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

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Ovarian gene expression is stable after exposure to trichloroethylene.

Wu Katherine Lily KL Berger Trish T

Toxicology letters 20071227 1

Exposure of female rats to trichloroethylene (TCE), an environmental toxicant commonly found in ground and surface waters throughout the United States, reduces the fertilizability of oocytes produced by these females compared with oocytes from control females. Localization of cytochrome P450 2E1 and glutathione s-transferase alpha, TCE-metabolizing enzymes, in the ovary suggests TCE metabolism occurs in the ovary. The production of bioactive TCE metabolites in the ovary may alter female reproduc ...[more]

PMID: 18249509

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Project description:Trichloroethylene (TCE) is a suspected renal carcinogen. TCE-associated renal genotoxicity occurs predominantly through glutathione S-transferase (GST) conjugation and bioactivation by renal cysteine beta-lyase (CCBL1). We conducted a case-control study in Central Europe (1,097 cases and 1,476 controls) specifically designed to assess risk associated with occupational exposure to TCE through analysis of detailed job histories. All jobs were coded for organic/chlorinated solvent and TCE exposure (ever/never) as well as the frequency and intensity of exposure based on detailed occupational questionnaires, specialized questionnaires, and expert assessments. Increased risk was observed among subjects ever TCE exposed [odds ratio (OR) = 1.63; 95% confidence interval (95% CI), 1.04-2.54]. Exposure-response trends were observed among subjects above and below the median exposure [average intensity (OR = 1.38; 95% CI, 0.81-2.35; OR = 2.34; 95% CI, 1.05-5.21; P(trend) = 0.02)]. A significant association was found among TCE-exposed subjects with at least one intact GSTT1 allele (active genotype; OR = 1.88; 95% CI, 1.06-3.33) but not among subjects with two deleted alleles (null genotype; OR = 0.93; 95% CI, 0.35-2.44; P(interaction) = 0.18). Similar associations for all exposure metrics including average intensity were observed among GSTT1-active subjects (OR = 1.56; 95% CI, 0.79-3.10; OR = 2.77; 95% CI, 1.01-7.58; P(trend) = 0.02) but not among GSTT1 nulls (OR = 0.81; 95% CI, 0.24-2.72; OR = 1.16; 95% CI, 0.27-5.04; P(trend) = 1.00; P(interaction) = 0.34). Further evidence of heterogeneity was seen among TCE-exposed subjects with >or=1 minor allele of several CCBL1-tagging single nucleotide polymorphisms: rs2293968, rs2280841, rs2259043, and rs941960. These findings provide the strongest evidence to date that TCE exposure is associated with increased renal cancer risk, particularly among individuals carrying polymorphisms in genes that are important in the reductive metabolism of this chemical, and provides biological plausibility of the association in humans.

Dataset Information

Ovarian gene expression is stable after exposure to trichloroethylene.

Publications

Ovarian gene expression is stable after exposure to trichloroethylene.

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