The Study On The Effect Of Nitrobenzene On The Reproduction Toxicity Mechanism In Male Mice

Nitrobenzene(NB) is used extensively in dye, medicine, pesticide, dynamite and so on as basic raw material in chemical engineering. It is also a material with a high toxicity. United States Environmental Protection Agency has put it in pollutant list of priority controlling. Some studies indicated that main harm of NB was liver, kidney and central nervous system. The report is still few about the effect of NB on reproductive system of the male mice. In this test, male KM mice were divided into three dose groups(low dose(26 mg/kg), middle dose(52 mg/kg),and high dose(105 mg/kg)) and each dose group respectively included natural control group and solvent control group. Low dose group and high dose group used intragastric administration lasting 30 days, and middle dose respectively lasting 10days, 20days and 30days. After those days, those mice were killed to detected toxicity of NB to testicle and glandula accessoria, T and FSH content and biochemical indicator change, antioxidative function, apoptosis, germ cell DNA damage, the expression of Bcl-2,Bax mRNA in germ cell and AR expression in order to explore the reproductive toxicity mechanism induced by NB. The result showed as follows:1. Detection of biochemical indicator in serum showed that NB induced decrease of ALP, SDH, r-GT and LDH activity and resulted in dysspermatogenesis.2. The content of T, FSH and the expression level of AR were respectively detected by radioimmunity assay and immunohistochemical method. The result showed that NB leaded to the decrease of T content and the increase of FSH content, which revealed damage of interstitial cell and Sertoli's cell. NB induced the decrease of AR expression level, which weakened regulation of AR to T transcription. These findings suggested that NB affected regulation of reproductive system and resulted in endocrine disturbance of reproductive system.3. The detection of antioxidative function revealed that the activity of SOD, CAT, GSH-Px and T-AOC were decreased and the content of MDA was increased in testis and serum. This showed that NB induced oxidative stress by the decrease of antioxidative function and this might be one of the maleness reproductive toxicity mechanism induced by NB.4. Apoptosis was detected by pathohistology observation, DNA Ladder, SCGE and TUNEL. The result showed that NB induced germ cell apoptosis and resulted in damage of genital system in male mice.5. The expression level of Bcl-2 and Bax mRNA was detected by RT-PCR. Bcl-2/Bax ratio was decreased obviously and this might be an important mechanism of NB inducing apoptosis.Above all, NB inhibited reproductive function of the male mice, destroyed antioxidative function, induced oxidative stress. In addition, NB interfered with Bcl-2,Bax mRNA expression level, and induced germ cell apoptosis. All these results showed reproductive toxicity of NB.In this study, reproductive toxicity of the male mice induced by NB was revealed from organic, cellular, subcellular and molecular level, and its toxicology mechanism was explained. These supplemented toxicology knowledge and provided evidence for evaluating male reproductive toxicity induced by NB.