| Organotin compounds ,such as tributyltin (TBT) have been widely used as wood preservatives ,biocides ,angriculture fungicides ,disinfection agnents in circulating industrial cooling waters ,as well as antifouling paints for marine vessels. Due to organotin compounds have been widely released into the waters . which have resulted in the environment pollution extremely. Organotin compounds not only destroy the ecological environment balance by poisoning the aquatic creature ,but also influence demic health for which can bioaccumulate in lipid of aquatic creature. The daily intake of TBT is estimated to be less than 1–10μg/person (approximately 0.02–0.2μg/kg body weight; Tsuda et al., 1995 ) even in Japan where people consume marine products in large quantities(In humans,a tolerable daily intake level of 0.25μg/kg has been proposed based on immunological toxicity).Up to now organotin compounds are considered as the one of most virulent chemical compounds due to human factor entered into the marine environment ,since which are found to pollute the marine. There is evidence that exposure to organotin compounds delay marint animal sex-maturity and multiply , and gastropoda animals imposex . Human exposue to organotin compounds cause kidey, liver ,guts ,systema respiratory ,intestines and stomach system ,genital system nervous system and immune system different toxic effect. And TBT causes growth inhibition, shell malformation and elevated mortality in oysters and mussels at low concentrations (Beaumont and Budd, 1984 and Alzieu et al., 1986) and it is well-known that TBT can induce imposex in females of 150 gastropod species at very low concentrations (Matthiessen et al., 1999), causing local extinction in severe cases. Although the toxicity of TBT has been well documented in marine species, there is a lack of a little is on mammalian,above all pubert mammalian. Here ,we researched effect of tribultytin chloride on reproductive development in pubert SD rats and mechanism.In vivo experiment ,The SD rats were exposed to tribultytin(TBT) from the 2 day after weaning at doses of 0.5mg/kg,2.5mg/kg,5.0mg/kg,7.5mg/kg,10.0mg/kg, respectively. The development of sexual organs and sex hormones levels of rats were determined. Immune histochemical analysis was also carried out to investigate the expression of Bax,Bc1-2, PCNA, ER and Aromatase.It shows that after continuously treated with TBT for 30days, the rats fed with 10.0mg/kg TBT had a significantly decreased of serum T level at the end of exposure. However a recreased serum E2 level was also found . Immune histological analysis showed that the expression of Bax in the epithlia of testis seminiferous tubules increased while the expression of Bcl-2 and PCNA decreased in three experiment groups indicating a lagged development in seminiferous tubules. Rats in experimental groups had weaker expression of ER of epithlia of testis seminiferous tubules than those in the control illustrating inhibition in various kinds of transcription and expression regulated by ER.Isolated and cultured the SD rat Sertoli cells in vitro , designed the direct exposure doses(20×10-9mol/L,40×10-9mol/L,80×10-9mol/L,120×10-9mol/L, solvent control group and blank control group) .The proliferation of the cells were detected by MTT assay,and the distribution of the cell cycles were analysed by FCM. The result shows that TBT can decrease the survival rate of Sertoli cells and interfere the distribution of the cell cycles. The result of immunocytochemistry shows that the expression of PCNA is inhibited in the 80×10-9mol/L and 120×10-9mol/L dose groups significantly,indicating that TBT inhibits the proliferation of Sertoli cells.The results of this study show that the possible mechanisms of obvious reproductive and developmental toxicity of TBT to SD rat is to influence the normal endocrine function, to result in increased apoptosis,decreased proliferation and inhibited transmission and expression of spermatogenic cells. Another possible mechanism is that TBT has damage in the adverse effect on the function of Sertoli cells and induces reproductive and developmental toxicity. |
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