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

Objectives The objectives of this study were to explore the chronic effects of low doses of TCDD on protein expression profiles in the rat testis/serum and to provide additional insight into the molecular mechanisms of TCDD reproductive and other toxicity.Methods A total of 32 male rats were randomly divided into three TCDD exposed groups(administrated 875,350 and 140 ng TCDD/kg/week for 29 weeks, respectively) and one control group(only received corn oil).The proteins from rat testis were separated and analyzed by two-dimensional gel electrophoresis and mass spectrometry(MALDI-TOF-MS and MALDI-TOF-MS/MS).Serum gonadal hormone concentration(testosterone/LH/FSH) was determined by ELISA.Sperm count/histopathology of testis and liver were performed simultaneously.Results The body weight of middle- and high-dose group were significantly lower than that of control group(P＜0.05).The relative testis weight of high-dose group and the relative liver weight of middle-and high-dose group were significantly higher than that of control group(P＜0.05).The number of sperm in middle- and high-dose group and serum gonadal hormone(testosterone,LH and FSH) concentration in high-dose group both decreased significantly compared with the control(P＜0.05).TCDD disturbs the testicular and serumal protein expression levels.Several interesting volume-altered proteins that were related to the reproductive or other toxicities of TCDD were identified.Among these proteins from testis,PERF15 was the only down-regulated protein;sperm protein SSP411,eukaryotic translation elongation factor 1 gamma(EF1B gamma),ubiquitin carboxyl-terminal hydrolase 13 (UCH-L3) and L-3-hydroxyacyl- CoA dehydrogenasee precursor were up-regulated by TCDD.Three differential proteins were identified in serum.Bal-647 was down-regulated protein;apolipoprotein E was up-regulated by TCDD and fetuin-like protein was only expressed in the group of 875 ng TCDD/kg/week.Besides,TCDD induced significant fatty degeneration and necrosis of liver in middle- and high-dose group(P＜0.05).The significant adipose degeneration and lytic necrosis of liver were observed in high-dose group.Conclusions The differentially expressed proteins and other data contribute to a better understanding of reproductive and other toxicity mediated by TCDD.In addition,the disorder of serum gonadal hormone induced by TCDD suggests that TCDD may interfere with the regulation mechanisms of hypothalamo-pituitary-gonadal axis;and the reproductive toxicity of TCDD partly attributed to the disorder of serum gonadal hormone.