| Objective:This study was designed to evaluate the estrogenic activity of cadmium and related mechanism,the destination was to demonstrate the female reproductive toxicity of cadmium.Methods:1. Immature rats were randomly divided into six group:the negative control group,four experiment groups(0.5,1,2,4 Cd2+ mg/kg·day) and the positive group (β-estradiol ).All rats were injected with the substance subcutaneouly once a day, three days altogether,then sacrificed on the fourth day. The uterine weight/body weight ratios were determined and uterine tissues were processed for histologic examination. Endometrial thickness,endometrial cavity epithelium cell thickness and endometrial stromal cell thickness were measured. The proliferating cell nucleus(PCNA) were examined using the immunohistochemical assay.2. The ovariectomize SD rats were random divided into six group:the negative control group,four experiment groups(0064,0.0320,0.1600, 0.8000 Cd2+mg/kg) and the positive group (β-estradiol ).All rats were injected with the drug intraperitoneally once a day, three days altogether,then sacrificed on the fourth day.the uterine weight/body weight ratios were determined and uterine tissues were processed forhistologic examination. Stained with hematoxylin and eosin, Endometrial thickness,endometrial cavity epithelium cell thickness and endometrial stromal cell thickness were measured;The number of endomentrial gland was counted; the ratio of endometrial stromal cell's Nuclear/cytoplasm was measured. The proliferating cell nucleus(PCNA) were examined using the immunohistochemical assay.3 MCF-7 cells were incubated with 10—12,10-10,10-8,10-6,10-4 ,10-2 mol/L Cd2+ and 10–mol/ Lβ-Estrodiol respectively, the OD of CCK-8 was 9 measure in the 2d,4d and 6d.4 MCF-7 cells were respectively incubated with 10—12,10-10,10-8,10- ,10-4 ,10-2 mol/L Cd2+ combined with 10–mol/ Lβ-Estrodiol, the 6 9 OD of CCK-8 was measure in the 2d,4d and 6d.Results:1 In the immature rats, the uterine weight and organ coefficients of uterus of the CdCl2 administration groups were not significantly different from the negative control group(p >0.05).but in the ovariectomize rats ,those of the CdCl2 administration groups were significantly different from the negative control group(p <0.05).2 There were no significant differences of the endometrial thickness between the negative control group and the CdCl2 administration groups in the immature rats(p>0.05). Nevertheless, in the ovariectomize rats, the endometrium of the highest dose cadmium administrated group(0.8000mg Cd2+/kg·day) was significantly thicker than negative control group(p <0.05). The endometrial cavity epithelium cell thickness of the CdCl2 administration groups was lower than the control group both in the immature rats and ovariectomize rats(p>0.05),However, in the ovariectomize rats, The endometrialcavity epithelium cell thickness of the β-estradiol administration group was significantly higher than the negative control( p<0.05).3 In the ovariectomize rats, the Nuclear/Cytoplasm ratios of endometrial cavity epithelium cell of the highest dose cadmium administrated group and the β-estradiol administration groups were significantly lower than the control group; β-estradiol could significant increase the number of Endometrial gland whereas cadmium can't.4 In immature rats, the positive rate of PCNA in the groups administrated with cadmium wasn't significantly different from that of the control groups. On the other hand, in the ovariectomize rats, the positive rate of PCNA in the groups administrated with highest dose cadmium was significantly lower than that of the control group. Compared with cadmium, β-estradiol could significant increase the positive rate of PCNA.5 In both animal models, there was positive correlation(p <0.001) between the uterine coefficient and the endometrial thickness. The correlation coefficient in the immature rats was 0.82 and in the ovariectomize rats was 0.83.In the ovariectomize rats there was negative correlation(p <0.05)between nuclear/cytoplasm ratios of endometrial cavity epithelium cells and uterine coefficients, the correlation coefficient was -0.36.6 MCF-7 cells didn′t proliferate when incubated with 10-12-10-6 mol/L Cd2+ , the effects of incubation time were significant(p<0.05), 10-4 -10-2 mol/L Cd2+ inhibited the proliferation of MCF-7. β-estradiol induced the proliferation of MCF-7,at the same time, the effects of incubation time were significant(p<0.05).7 Compared with the MCF-7 cells incubated with 10-12-10-6 mol/L Cd2+ alone,the MCF-7 cells incubated with 10-12-10-6 mol/L Cd2+and 10-9β-estradiol together showed less proliferation(p<0.05). Compared with the MCF-7 cells incubated with 10-9β-estradiol alone, the MCF-7 cells incubated with 10-12-10-6 mol/L Cd2+and 10-9β-estradiol together also showed less proliferation(p<0.05).The effects of incubation time were significant(p<0.05)Conclusions:1. Under our experimental conditions, in the ovariectomize rats, high doses of cadmium could induce the increasement of the uterine weight ﹑the organ coefficient of uterus and the endometrial thickness. However in the immature rats, these effects couldn't be observed.2. In the immature rats, cadmium induced the increasement of the uterine weight not by the mechanism of cell proliferation other than β-estradiol.3. Under our experimental conditions, cadmium couldn't make the MCF-7 cells proliferate in vitro.4. β-estradiol could enhance the cytotoxicity of cadmium... |
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