| Phthalates are widely used as plasticizers in industry and our daily life, because they can increase the flexibility and tenacity of plastic. The di-n-butyl phthalate (DBP), a kind of phthalates, is the largest amount of plasticizer used currently in China, and its hazard of reproductive and developmental dysfunction has been concerned in recent years. The main objectives of this study are to investigate oxidative damage and reproductive toxicity of DBP to male mice by analysis of the activity of the superoxide dismutase (SOD), the content of GSH and MDA in liver, histopathological changes, enzyme activities, and hormone and gene transcription levels in testis. A comprehensive understanding of toxicity of DBP on reproduction should allow biologically based dose response models to be used in the risk assessment process, which are then likely to lead to a more realistic appraisal of the human risks associated with exposure to DBP at environmentally relevant levels.1. Oxidative damage in liver of mice caused by DBPIn order to estimate the oxidative damage induced by DBP in liver of mice, mice were exposed to DBP by gastric intubation with different concentrations (0,125,250, 500 and 1000 mg/kg) for 40 days, and then SOD activity, the content of GSH and MDA in liver were measured. The results showed that the activity of SOD has significantly decreased (p<0.01) at the concentration of 250,500 and 1000 mg/kg compared with the peanut oil group (control). The contents of GSH were decreased, and there was a significant difference (p<0.05) at the concentration of 125 mg/kg and extremely significant differences (p<0.01) were detected at the concentration of 250,500 and 1000 mg/kg compared to the control group. The contents of MDA were significantly increased (p<0.01) at the concentration of 250,500 and 1000 mg/kg, but no obviously decrease at the concentration of 125 mg/kg. It showed that with the increase of DBP concentration, the lipid peroxidation products increased. The change of liver coefficient showed that the increase of liver weight, indicating that the liver had swollen after exposure.2. Testis damage of mice by DBPComparing with the testis slice of exposure groups with control group, it could be seen that the seminiferous tubules were filled with spermatogonia, spermatocytes and spermatids in control group. As the dose of DBP increased, seminiferous tubules were shrank and semen, spermatcytes, sperm cells declined. Especially at the 1000 mg/kg dose, the obvious atrophy of seminiferous tubules was observed. The result showed that testis was damaged by DBP, suggesting that DBP can disturb normal development of testis, and the damage degree was positively associated with the DBP dose. The decline of liver coefficient was correlated with the decrease of testis weight, indicating that testis atrophy occurred. The result of sperm count in epididymis showed that the number of sperm decreased after exposed to DBP. The content of MDA in testis increased compared with the control, characterized by the increase of lipid peroxidation product and there were extremely significant differences at the concentration of 125 mg/kg and 250 mg/kg (p<0.01), and significant differences at the concentration of 500 mg/kg and 1000 mg/kg (p<0.05). Our data indicated that reproductive toxicity of DBP may be generated via oxidative damage.3. Effects of DBP on the activity of SDH in testisSuccinic dehydrogenase (SDH) is an indispensable enzyme in energy metabolism of germ cells. The reduction of SDH activity in the mice after treated with different concentrations of DBP showed. Compared to the control, the activity of SDH in the all exposure groups were lower, but with significant differences (p<0.01) at the concentration of 250,500 and 1000 mg/kg. The result indicated that DBP can affect the usage of Germ cells, which would induce reproductive toxicity.4. Effects of DBP on the FSH level in the serumFollicle stimulating hormone (FSH) is an important factor in spermatogenesis and to evaluation whether Sertoli cells were damaged or not. FSH can interact with its receptor on Sertoli cells, promoting the synthesis of ABP. If Sertoli cells were damaged, then the receptor of FSH would decrease and the concentration of FSH would increase. The result showed that FSH concentration significantly increased only at the highest dose (1000 mg/kg) compared to the control group (p<0.01), although slight increase was also noted at the 125,250 and 500 mg/kg doses.5. Effects of DBP on the transcription of ABP gene in testisAndrogen binding protein (ABP) can combine with the testosterone specifically in order to maintain a high concentration of testosterone in serum or seminiferous tubule. The changes of androgen binding protein ABP expression directly affect the development of spermatogenic cells. The result of RT-PCR showed that the transcription of ABP was significantly decreased at the concentration of 125 mg/kg of DBP compared with peanut oil group (p<0.01). However, a significantly increase were observed at concentration of 250,500,1000 mg/kg of DBP (p<0.01). |
PDF Full Text Request