Proteomic Analysis Of The Rat Ovary And Serum Following Chronic Exposure With TCDD

Objectives 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) is a ubiquitously distributed endocrine-disrupting chemical and reproductive toxicant.To elucidate its reproductive or endocrine toxicity and to investigate the differences of ovary and serum protein expression especially around the low-dose range with chronic exposure.Methods 32 female Sprague-Dawley rats were administered orally various concentrations(Ong·kg^-1·d^-1,20ng·kg^-1·d^-1,50ng·kg^-1·d^-1,125ng·kg^-1·d^-1) of TCDD for 29 weeks.Proteomic analysis of ovary and serum by two-dimensional gel electrophoresis and MALDI Tandem Mass Spectrometry showed distinct changes in the levels of several proteins that are relevant to TCDD toxicity.The hepatic histopathology was also performed after the sacrifice.Results Serum estradiol levels of TCDD-treated animals were reduced remarkably compared with the controls.There were no significant differences in the mean of the bone mineral density(BMD) of femurs,although in the control group there was less variation in the individual BMD.The body weight of the 125 ng/kg/d group was significantly decreased relative to the controls and there was also a significant reduction in absolute and relative ovary weight.Selenium binding protein 2, Glutathione S-transferase mu type 3,Lrpapl protein,NADPH,and Peptidylprolyl isomerase D were up-regulated,while Prohibitin and N-ethylmaleimide sensitive factor had depressed levels.The severity of the lesions(adipose degeneration,cytoplasmic vacuolization,cell necrosis etc.) increased with the treated concentration.The 125ng·kg^-1·d^-1 group had a significantly lower body weight and higher absolute liver weight relative to the control group.There was also a significant increase in relative liver weight of the TCDD treated groups compared with controls.Complement component 4, Preaploipoprotein A-IV and LMW T-kininogen 1 precursor were up-regulated. Haptoglobin and Complement component 3 were found in TCDD treated groups but not in the control group,while alpha-1-inhibitorⅢprecursor was only present in the control group. ConclusionsThe study give clues to the mechanisms of endocrine toxicity,immunotoxicity, hepatotoxicity and oxidative toxicity mediated by TCDD.Especially,the data provide further insight into the mechanisms by which TCDD disrupts ovarial function by showing which ovarial proteins are affected by TCDD exposure.