• Home
  • Search Results
  • Testicular gene expression profiling following 2-methoxyethanol and 2-ethoxyethanol exposure in male rats reveals abnormal expression of the actin binding protein cortactin in degenerating spermatocytes.

Testicular gene expression profiling following 2-methoxyethanol and 2-ethoxyethanol exposure in male rats reveals abnormal expression of the actin binding protein cortactin in degenerating spermatocytes.

Toxicology letters (2009-08-01)
Elizabeth G Tonkin, Matthew Cooper, Lance O Lollini, Patricia A Day-Lollini, John Allard, Kyle L Kolaja, Stefan J Platz, Sushmita M Chanda
ABSTRACT

The glycol ether solvents 2-methoxyethanol (2-ME) and 2-ethoxyethanol (2-EE) produce testicular toxicity characterized by spermatocyte degeneration, while a similar glycol ether, 2-butoxyethanol (2-BE), has no testicular effects. The goal of the current study was to better understand the mechanism of glycol ether testicular toxicity through gene expression profiling and functional classification of differentially expressed genes. Male rats were administered 2-ME (150 and 50mg/kg/day), 2-EE (500 mg/kg/day), 2-BE (125 mg/kg/day), or vehicle for 3 days, and testes were collected for histopathological and gene expression analysis. Histopathological changes in the testes were observed only in animals given 150 mg/kg/day 2-ME, consisting of degeneration and necrosis of spermatocytes and reductions in spermatocyte numbers. Microarray analysis of testicular samples from these animals revealed a large number of differentially expressed genes from animals exposed to 2-EE or to 50mg/kg or 150 mg/kg 2-ME (>900 each at >1.5-fold changed), compared to 28 genes from 2-BE treated animals. Expression Analysis Systematic Explorer (EASE) analysis of these genes demonstrated statistical enrichment in genes in categories including protein transport, endocytosis, protein kinase activity, cell cycle, and meiosis. Quantitative PCR confirmation of select genes confirmed increased expression of the actin binding protein cortactin and the transcription factor Wilm's tumor 1 (Wt1) following 2-ME exposure. Increased localization of cortactin in abnormal spermatocytes was also observed by immunohistochemistry, consistent with a possible role for this protein in the mechanism of toxicity.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
2-Methoxyethanol, anhydrous, 99.8%
Sigma-Aldrich
2-Ethoxyethanol, ReagentPlus®, 99%
Sigma-Aldrich
2-Methoxyethanol, suitable for HPLC, ≥99.9%
Sigma-Aldrich
2-Methoxyethanol, ReagentPlus®, ≥99.0%, contains 50 ppm BHT as stabilizer
Supelco
2-Ethoxyethanol, analytical standard
Sigma-Aldrich
2-Methoxyethanol, contains 50 ppm BHT as stabilizer, ACS reagent, ≥99.3%
Supelco
2-Methoxyethanol, analytical standard
Sigma-Aldrich
2-Ethoxyethanol, spectrophotometric grade, ≥99%