Proteomic Analysis of the Rat Ovary Following Chronic Low-Dose Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD)

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitously distributed endocrine-disrupting chemical and reproductive toxicant. In order to elucidate low-dose TCDD-mediated effects on reproductive or endocrine functions, female Sprague-Dawley rats were orally administered various concentrations (20, 50, or 125 ng/kg once weekly) TCDD for 29 wk. A proteomic analysis of the ovaries by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization (MALDI) tandem mass spectrometry showed distinct changes in the levels of several proteins that are relevant markers of TCDD toxicity. Serum estradiol (E2) levels of TCDD-treated animals were markedly lower than control. There were no significant differences in bone mineral density (BMD) of femurs. The body weight of the 125-ng/kg TCDD group was significantly decreased relative to control and there was also a significant reduction in absolute and relative ovarian weights. Expressions of selenium binding protein 2, glutathione S-transferase mu type 3, Lrpap1 protein, NADPH, and peptidylprolyl isomerase D were upregulated, while prohibitin and N-ethylmaleimide-sensitive factor expression levels were downregulated. Data provide further insight into the mechanisms by which TCDD disrupts ovarian function by indicating which differential protein expressions following low-dose TCDD exposure.