Effects of endocrine disrupting chemicals on expression of phospholipid hydroperoxide glutathione peroxidase mRNA in rat testes

J Vet Sci. 2007 Sep;8(3):213-8. doi: 10.4142/jvs.2007.8.3.213.

Abstract

Phospholipid hydroperoxide glutathione peroxidase (PHGPx), an antioxidative selenoprotein, is modulated by estrogen in the testis and oviduct. To examine whether potential endocrine disrupting chemicals (EDCs) affect the microenvironment of the testes, the expression patterns of PHGPx mRNA and histological changes were analyzed in 5-week-old Sprague-Dawley male rats exposed to several EDCs such as an androgenic compound [testosterone (50, 200, and 1,000 microg/kg)], anti-androgenic compounds [flutamide (1, 5, and 25 mg/kg), ketoconazole (0.2 and 1 mg/kg), and diethylhexyl phthalate (10, 50, and 250 mg/kg)], and estrogenic compounds [nonylphenol (10, 50, 100, and 250 mg/kg), octylphenol (10, 50, and 250 mg/kg), and diethylstilbestrol (10, 20, and 40 microg/kg)] daily for 3 weeks via oral administration. Mild proliferation of germ cells and hyperplasia of interstitial cells were observed in the testes of the flutamide-treated group and deletion of the germinal epithelium and sloughing of germ cells were observed in testes of the diethylstilbestrol-treated group. Treatment with testosterone was shown to slightly decrease PHGPx mRNA levels in testes by the reverse transcriptionpolymerase chain reaction. However, anti-androgenic compounds (flutamide, ketoconazole, and diethylhexyl phthalate) and estrogenic compounds (nonylphenol, octylphenol, and diethylstilbestrol) significantly upregulated PHGPx mRNA in the testes (p < 0.05). These findings indicate that the EDCs might have a detrimental effect on spermatogenesis via abnormal enhancement of PHGPx expression in testes and that PHGPx is useful as a biomarker for toxicity screening of estrogenic or antiandrogenic EDCs in testes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / pharmacology
  • Animals
  • Diethylhexyl Phthalate / pharmacology
  • Diethylstilbestrol / pharmacology
  • Endocrine Disruptors / pharmacology*
  • Estrogens, Non-Steroidal / pharmacology
  • Flutamide / pharmacology
  • Glutathione Peroxidase / biosynthesis*
  • Glutathione Peroxidase / genetics
  • Histocytochemistry
  • Ketoconazole / pharmacology
  • Male
  • Phenols / pharmacology
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spermatogenesis / drug effects
  • Testis / drug effects*
  • Testis / enzymology*
  • Testosterone / pharmacology

Substances

  • Androgen Antagonists
  • Endocrine Disruptors
  • Estrogens, Non-Steroidal
  • Phenols
  • RNA, Messenger
  • octylphenol
  • Testosterone
  • Diethylstilbestrol
  • Flutamide
  • nonylphenol
  • Diethylhexyl Phthalate
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • Glutathione Peroxidase
  • Ketoconazole