Comparision And Research On The Increasing Of Uterus Weight And Related Mechanisms Of Cadmium And P-nonylphenol

Objective:The research was designed to compare the effects of increasing of uterine wet weight induced by cadmium and p-nonylphenol, and investigate the related mechanisms and provide scientific evidence for elucidating estrogenic effects and related mechanism of different categories of EEDs.Methods:Sixty ovariectomized SD immature rats were randomly divided into six groups by weight:negative control(ultrapure water),two cadmium groups(0.12,1.20mg/kgCd2+),two p-nonylphenol groups(100,200mg/kg NP) and positive control(0.03mg/kgβ-estradiol).All the rats were administrated with the drugs respectively by intraperitoneal injection once a day, lasting three days, and sacrificed on the fourth day. Body weight,uterus wet weight,uterus coefficient were measured, and uterus tissues were processed for histologic and immunohistochemistry examination; Serum of rats was prepared for detecting the sexual hormone levels; uterus tissues were homogenated for exploring the expression of ERK1/2 and p-ERK1/2 by western blot.Results:1. The uterus wet weight and uterus coefficient in the higher dose CdCl2 group were significantly increased (P<0.01); both high and low dose NP and positive control groups were significantly increased (P<0.01) in these indexes.2. In the group of higher dose CdCl2, thickness of luminal epithelial cell and endometrium were higher than negative control (P<0.01), and nuclear/cytoplasm of luminal epithelial cell and endometrium were decreased (P<0.01); In the group of lower dose CdCl2, thickness and nuclear/cytoplasm of luminal epithelial cell was higher and lower than negative control respectively (P<0.05); both high and low dose NP and positive control groups were significantly different from negative control in these indexes(P<0.01).3. The positive rate of PCNA in the group of higher dose CdCl2 was lower than negative control (P<0.05), which was higher in both high and low dose NP and positive control groups.4. E2 and P4 levels from serum in the group of higher dose CdCl2 were lower than negative control (P<0.05); there were no significant differences in both high and low dose NP groups in these indexes (P>0.05).5. FSH and LH levels from serum in the group of lower dose CdCl2 were lower than negative control (P<0.01,P<0.05); There were no significant differences in both high and low dose NP groups in these indexes (P>0.05).6. There were significant differences of p-ERK1/ERK1 and p-ERK2/ERK2 between the group of higher dose CdCl2 and negative control(P<0.01); There were also significant differences of these indexes between the two NP, positive control groups and negative control (P<0.01,P<0.05).Conclusion:1. Under this experiment conditions, cadmium(1.20 mg/kgCd2+) and p-nonylphenol(100,200mg/kgNP) could induce the increase of uterus weight and uterus coefficient;2. There were differences of mechanisms induced by between cadmium and p-nonylphenol. The mechanism of p-nonylphenol was similar toβ-estradiol, which mainly caused cell proliferation of uterus; But that was not the mechanism of cadmium.3. Under this experiment conditions, both cadmium and p-nonylphenol could evoke MAPK(ERK)path, thus displayed respective effects of endocrine disruption.